Research Publications
Browse scientific publications from the NIH-funded RDCRN network and its 21 consortia or research teams to find information about rare disease research and read rare disease publications. Publications are sorted by consortium and year.
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Koskimäki J, Jhaveri A, Srinath A, Bindal A, Vera Cruz D, Priyanka Yeradoddi G, Lightle R, Lee J, Stadnik A, Iqbal J, Alcazar-Felix R, Hage S, Romanos S, Shenkar R, Loeb J, Faughnan ME, Weinsheimer S, Kim H, Girard R, Awad IA. Common and distinct circulating microRNAs in four neurovascular disorders. Biochem Biophys Rep. 2025 Aug 2;43:102189. doi: 10.1016/j.bbrep.2025.102189. PMID: 40800603; PMCID: PMC12341739.
Familial cerebral cavernous malformations (FCCM), Sturge-Weber syndrome (SWS), and hereditary hemorrhagic telangiectasia (HHT) are neurovascular disorders caused by genetic mutations that can lead to brain bleeding. Cerebral microbleeds (CMBs) are another type of neurovascular disorder that causes brain bleeding. However, CMBs are more often associated with the aging process than genetic factors.
In this study, researchers compared circulating microRNAs in these four neurovascular disorders. First, the team identified differentially expressed plasma microRNAs from patients with FCCM, SWS, HHT, and CMB. Next, they used analysis techniques to identify gene targets of the differentially expressed microRNAs and their associated pathways.
Results revealed both similarities and differences in microRNAs. Among all four disorders, dysregulated microRNAs targeted the PI3K-Akt and ROBO SLIT signaling pathways. Authors note that these findings reveal shared mechanistic pathways underlying vascular dysmorphism and bleeding, highlighting their potential use for disease monitoring and therapeutic intervention.
DeBose-Scarlett E, Ressler AK, Friday C, Prickett KK, Roberts JW, Gossage JR, Marchuk DA. Arteriovenous malformation from a patient with JP-HHT harbours two second-hit somatic DNA alterations in SMAD4. J Med Genet. 2025 Mar 20;62(4):281-288. doi: 10.1136/jmg-2024-110569.
Beslow LA, Kim H, Hetts SW, Ratjen F, Clancy MS, Gossage JR, Faughnan ME. Brain and lung arteriovenous malformation rescreening practices for children and adults with hereditary hemorrhagic telangiectasia. Orphanet J Rare Dis. 2024 Nov 9;19(1):421. doi: 10.1186/s13023-024-03402-8. PMID: 39522006; PMCID: PMC11549847.
Hereditary hemorrhagic telangiectasia (HHT) is an inherited disorder of the blood vessels that can cause excessive bleeding. Patients with HHT are at risk for organ vascular malformations, including arteriovenous malformations (AVMs) in the brain and lungs. Although HHT guidelines recommend initial screening in children and adults, rescreening is not consistently addressed.
In this study, researchers determined current rescreening practices for brain and lung AVMs in children and adults with HHT. The team surveyed 30 North American HHT Centers of Excellence on rescreening practices for new brain and lung AVMs in patients with initial negative screening.
Results show that most HHT Centers of Excellence routinely rescreen children for brain and lung AVMs and adults for lung AVMs when initial screening is negative. However, adults are infrequently rescreened for brain AVMs. Authors note that long-term data regarding risk for new brain and lung AVMs are required to establish practice guidelines for rescreening.
DeBose-Scarlett E, Ressler AK, Gallione CJ, Sapisochin Cantis G, Friday C, Weinsheimer S, Schimmel K, Spiekerkoetter E, Kim H, Gossage JR, Faughnan ME, Marchuk DA. Somatic mutations in arteriovenous malformations in hereditary hemorrhagic telangiectasia support a bi-allelic two-hit mutation mechanism of pathogenesis. Am J Hum Genet. 2024 Oct 3;111(10):2283-2298. doi: 10.1016/j.ajhg.2024.08.020. Epub 2024 Sep 18.
Juhász C, Behen ME, Gjolaj N, Luat AF, Xuan Y, Jeong JW. Feasibility and Potential Diagnostic Value of Noncontrast Brain MRI in Nonsedated Children With Sturge-Weber Syndrome and Healthy Siblings. J Child Neurol. 2024 Aug;39(9-10):343-353. doi: 10.1177/08830738241272064. Epub 2024 Aug 23.
Beslow LA, Krings T, Kim H, Hetts SW, Lawton MT, Ratjen F, Whitehead KJ, Gossage JR, McCulloch CE, Clancy M, Bagheri N, Faughnan ME. De Novo Brain Vascular Malformations in Hereditary Hemorrhagic Telangiectasia. Pediatr Neurol. 2024 Jun;155:120-125. doi: 10.1016/j.pediatrneurol.2024.03.013. Epub 2024 Mar 22. PMID: 38631080; PMCID: PMC11102835.
Hereditary hemorrhagic telangiectasia (HHT) is an inherited disorder of the blood vessels that can cause excessive bleeding. About 10% of individuals with HHT have brain vascular malformations, which occur when the blood vessels in the brain develop abnormally. Children with HHT are screened for brain vascular malformations upon initial diagnosis, and many North American centers rescreen children for brain vascular malformations at interval throughout childhood. However, not much is known about whether people with HHT can develop new brain vascular malformations over time.
In this study, researchers investigated the formation of new brain vascular malformations in patients with HHT. The team analyzed data from 1,909 patients enrolled in the Brain Vascular Malformation Consortium natural history study, searching for brain vascular malformations that were new since previous imaging was performed.
Results showed that 409 patients had brain vascular malformations, with three showing new malformations confirmed by neuroimaging review. These findings demonstrate that patients with HHT can form new brain vascular malformations over time, though this is probably a rare occurrence. Authors note that more information about the frequency of new brain vascular malformation formation is needed.
Frias-Anaya E, Gallego-Gutierrez H, Gongol B, Weinsheimer S, Lai CC, Orecchioni M, Sriram A, Bui CM, Nelsen B, Hale P, Pham A, Shenkar R, DeBiasse D, Lightle R, Girard R, Li Y, Srinath A, Daneman R, Nudleman E, Sun H, Guma M, Dubrac A, Mesarwi OA, Ley K, Kim H, Awad IA, Ginsberg MH, Lopez-Ramirez MA. Mild Hypoxia Accelerates Cerebral Cavernous Malformation Disease Through CX3CR1-CX3CL1 Signaling. Arterioscler Thromb Vasc Biol. 2024 Jun;44(6):1246-1264. doi: 10.1161/ATVBAHA.123.320367. Epub 2024 Apr 25.
Beslow LA, Vossough A, Kim H, Nelson J, Lawton MT, Pollak J, Lin DDM, Ratjen F, Hammill AM, Hetts SW, Gossage JR, Whitehead KJ, Faughnan ME, Krings T; Brain Vascular Malformation Consortium HHT Investigator Group. Brain AVM compactness score in children with hereditary hemorrhagic telangiectasia. Childs Nerv Syst. 2024 Mar 22. doi: 10.1007/s00381-024-06366-z. Online ahead of print.
Jeong JW, Lee MH, Luat AF, Xuan Y, Haacke EM, Juhász C. Quantification of enlarged deep medullary vein volumes in Sturge-Weber syndrome. Quant Imaging Med Surg. 2024 Feb 1;14(2):1916-1929. doi: 10.21037/qims-23-1271. Epub 2024 Jan 23. PMID: 38415136; PMCID: PMC10895099.
Sturge-Weber syndrome (SWS) is a condition resulting in abnormal blood vessel formation in the brain, eyes, and skin at birth. In patients with SWS, enlarged deep medullary veins—mostly located in the white matter in the brain—may form early and can expand during the first years of life to provide compensatory collateral venous drainage of brain regions affected by leptomeningeal venous malformations localized on the brain surface.
The extent of enlarged deep veins during the early SWS disease course could be an imaging marker of this deep venous remodeling in an attempt to compensate for impaired brain surface venous blood flow. In this prospective imaging study, researchers used brain magnetic resonance imaging (MRI) to develop and optimize a quantitative approach to measure deep vein volumes in the affected brain of young patients with SWS and compare the findings to those of their healthy siblings.
By combining two types of MRI (susceptibility-weighted imaging and volumetric T1 images), the authors were able to measure the volumes of deep veins, which were 10-12 fold higher than venous volumes in their healthy siblings. Greater deep vein volumes were associated with lower cortical surface area of the affected hemisphere, a measure of cortical atrophy. This new analytic approach of brain MRI can provide an objective way to assess the extent of deep venous remodeling in SWS and other disorders affecting the medullary veins of the brain.
Cheng HC, Faughnan ME, terBrugge KG, Liu HM, Krings T; Brain Vascular Malformation Consortium Hereditary Hemorrhagic Telangiectasia Investigator Group. Prevalence and Characteristics of Intracranial Aneurysms in Hereditary Hemorrhagic Telangiectasia. AJNR Am J Neuroradiol. 2023 Dec 11;44(12):1367-1372. doi: 10.3174/ajnr.A8058. PMID: 38050014; PMCID: PMC10714847.
Tuff-Gordon E, Faughnan ME, Kim H, Lawton MT, Vozoris NT; Brain Vascular Malformation Consortium HHT Investigator Group; Brain Vascular Malformation Consortium HHT Investigator Group. An analysis of sex differences in pulmonary arteriovenous malformation presentation, complications and management in a large, multinational registry of patients with hereditary haemorrhagic telangiectasia. ERJ Open Res. 2023 May 22;9(3):00751-2022. doi: 10.1183/23120541.00751-2022. eCollection 2023 May.
Kim SJW, Lupo JM, Chen Y, Pampaloni MH, VanBrocklin HF, Narvid J, Kim H, Seo Y. A feasibility study for quantitative assessment of cerebrovascular malformations using flutriciclamide ([(18)F]GE-180) PET/MRI. Front Med (Lausanne). 2023 Apr 5;10:1091463. doi: 10.3389/fmed.2023.1091463. eCollection 2023.
Kilian A, Latino GA, White AJ, Ratjen F, McDonald J, Whitehead KJ, Gossage JR, Krings T, Lawton MT, Kim H, Faughnan ME, The Brain Vascular Malformation Consortium Hht Investigator Group. Comparing Characteristics and Treatment of Brain Vascular Malformations in Children and Adults with HHT. J Clin Med. 2023 Apr 4;12(7):2704. doi: 10.3390/jcm12072704.
Cannavicci A, Zhang Q, Kutryk MJB. The Potential Role of MiRs-139-5p and -454-3p in Endoglin-Knockdown-Induced Angiogenic Dysfunction in HUVECs. Int J Mol Sci. 2023 Mar 3;24(5):4916. doi: 10.3390/ijms24054916.
Weinsheimer S, Nelson J, Abla AA, Ko NU, Tsang C, Okoye O, Zabramski JM, Akers A, Zafar A, Mabray MC, Hart BL, Morrison L, McCulloch CE, Kim H; Brain Vascular Malformation Consortium Cerebral Cavernous Malformation Investigator Group. Intracranial Hemorrhage Rate and Lesion Burden in Patients With Familial Cerebral Cavernous Malformation. J Am Heart Assoc. 2023 Feb 7;12(3):e027572. doi: 10.1161/JAHA.122.027572. Epub 2023 Jan 25. PMID: 36695309; PMCID: PMC9973654.
Familial cerebral cavernous malformation (CCM) is an inherited disease characterized by abnormally enlarged spaces in the brain where blood collects near irregularly shaped, enlarged capillaries (tiny blood vessels) which have abnormally thin walls prone to leaking. CCM can cause intracranial hemorrhage (ICH), which can lead to death or long-term neurological damage. However, few studies have focused on ICH rates and risk factors in familial CCM.
In this study, researchers report ICH rates and assess whether CCM lesion burden—a disease severity marker—is associated with risk of symptomatic ICH in familial CCM. The team studied 386 patients with familial CCM with follow‐up data enrolled in the Brain Vascular Malformation Consortium CCM Project.
Results show that patients with familial CCM with a prior history of an ICH event are at higher risk for rehemorrhage during follow‐up. In addition, CCM lesion burden is significantly associated with an increased risk of subsequent symptomatic ICH. Authors note that these findings demonstrate the importance of lesion burden as a predictor of patient outcomes, which can also help to assess patient risk.
Juhász C, Luat AF, Behen ME, Gjolaj N, Jeong JW, Chugani HT, Kumar A. Deep Venous Remodeling in Unilateral Sturge-Weber Syndrome: Robust Hemispheric Differences and Clinical Correlates. Pediatr Neurol. 2023 Feb;139:49-58. doi: 10.1016/j.pediatrneurol.2022.11.011. Epub 2022 Nov 25. PMID: 36521316; PMCID: PMC9840672.
Sturge-Weber syndrome (SWS) is a condition resulting in abnormal blood vessel development in the brain, eyes, and skin at birth. In patients with SWS, enlarged deep medullary veins (EDMVs)—located in the white matter in the brain—could allow for drainage of brain regions affected by leptomeningeal venous malformations (LVM), a type of vascular malformation of the brain. In this study, researchers evaluated the prevalence, extent, hemispheric differences, and clinical correlates of EDMVs in SWS. Fifty children with SWS underwent brain magnetic resonance imaging that included susceptibility weighted imaging, as well as neurocognitive evaluations. The team then assessed the extent of EDMVs, comparing between patients with right and left hemispheric SWS. Results show that EDMVs are common in SWS. For patients with right hemispheric SWS, extensive EDMVs appear to develop more commonly and earlier than in left hemispheric SWS. Authors note that deep venous remodeling may contribute to better clinical outcomes in some patients with SWS.
Yeom S, Comi AM. Updates on Sturge-Weber Syndrome. Stroke. 2022 Dec;53(12):3769-3779. doi: 10.1161/STROKEAHA.122.038585. Epub 2022 Oct 20.
Galeffi F, Snellings DA, Wetzel-Strong SE, Kastelic N, Bullock J, Gallione CJ, North PE, Marchuk DA. A novel somatic mutation in GNAQ in a capillary malformation provides insight into molecular pathogenesis. Angiogenesis. 2022 May 30. doi: 10.1007/s10456-022-09841-w. Epub ahead of print. PMID: 35635655.
Ananiadis T, Faughnan ME, Clark D, Prabhudesai V, Kim H, Lawton MT, Vozoris NT; Brain Vascular Malformation Consortium HHT Investigator Group. Neurovascular Complications and Pulmonary Arteriovenous Malformation Feeding Artery Size. Ann Am Thorac Soc. 2022 Apr 20. doi: 10.1513/AnnalsATS.202202-130RL. Online ahead of print.
Winkler E, Wu D, Gil E, McCoy D, Narsinh K, Sun Z, Mueller K, Ross J, Kim H, Weinsheimer S, Berger M, Nowakowski T, Lim D, Abla A, Cooke D. Endoluminal Biopsy for Molecular Profiling of Human Brain Vascular Malformations. Neurology. 2022 Apr 19;98(16):e1637-e1647. doi: 10.1212/WNL.0000000000200109. Epub 2022 Feb 10.
Cannavicci A, Zhang Q, Faughnan ME, Kutryk MJB. MicroRNA-132-3p, Downregulated in Myeloid Angiogenic Cells from Hereditary Hemorrhagic Telangiectasia Patients, Is Enriched in the TGFβ and PI3K/AKT Signalling Pathways. Genes (Basel). 2022 Apr 9;13(4):665. doi: 10.3390/genes13040665.
Winkler EA, Kim CN, Ross JM, Garcia JH, Gil E, Oh I, Chen LQ, Wu D, Catapano JS, Raygor K, Narsinh K, Kim H, Weinsheimer S, Cooke DL, Walcott BP, Lawton MT, Gupta N, Zlokovic BV, Chang EF, Abla AA, Lim DA, Nowakowski TJ. A single-cell atlas of the normal and malformed human brain vasculature. Science. 2022 Mar 4;375(6584):eabi7377. doi: 10.1126/science.abi7377. Epub 2022 Mar 4.
Sheth KN, Anderson CD, Biffi A, Dlamini N, Falcone GJ, Fox CK, Fullerton HJ, Greenberg SM, Hemphill JC, Kim A, Kim H, Ko NU, Roland JL, Sansing LH, van Veluw SJ, Rosand J. Maximizing Brain Health After Hemorrhagic Stroke: Bugher Foundation Centers of Excellence. Stroke. 2022 Mar;53(3):1020-1029. doi: 10.1161/STROKEAHA.121.036197. Epub 2022 Feb 3.
Cardinell JL, Ramjist JM, Chen C, Shi W, Nguyen NQ, Yeretsian T, Choi M, Chen D, Clark DS, Curtis A, Kim H, Faughnan ME, Yang VXD; Brain Vascular Malformation Consortium HHT Investigator Group. Quantification metrics for telangiectasia using optical coherence tomography. Sci Rep. 2022 Feb 2;12(1):1805. doi: 10.1038/s41598-022-05272-1.
Narsinh KH, Paez R, Mueller K, Caton MT, Baker A, Higashida RT, Halbach VV, Dowd CF, Amans MR, Hetts SW, Norbash AM, Cooke DL. Robotics for neuroendovascular intervention: Background and primer. Neuroradiol J. 2022 Feb;35(1):25-35. doi: 10.1177/19714009211034829. Epub 2021 Aug 16.
Gill RE, Tang B, Smegal L, Adamek JH, McAuliffe D, Lakshmanan BM, Srivastava S, Quain AM, Sebold AJ, Lin DDM, Kossoff EH, Caffo B, Comi AM, Ewen JB. Quantitative EEG improves prediction of Sturge-Weber syndrome in infants with port-wine birthmark. Clin Neurophysiol. 2021 Oct;132(10):2440-2446. doi: 10.1016/j.clinph.2021.06.030. Epub 2021 Aug 5.
Thompson KP, Nelson J, Kim H, Weinsheimer SM, Marchuk DA, Lawton MT, Krings T, Faughnan ME; Brain Vascular Malformation Consortium HHT Investigator Group. Utility of modified Rankin Scale for brain vascular malformations in hereditary hemorrhagic telangiectasia. Orphanet J Rare Dis. 2021 Sep 19;16(1):390. doi: 10.1186/s13023-021-02012-y.
Choksi F, Weinsheimer S, Nelson J, Pawlikowska L, Fox CK, Zafar A, Mabray MC, Zabramski J, Akers A, Hart BL, Morrison L, McCulloch CE, Kim H. Assessing the association of common genetic variants in EPHB4 and RASA1 with phenotype severity in familial cerebral cavernous malformation. Mol Genet Genomic Med. 2021 Sep 7:e1794. doi: 10.1002/mgg3.1794. Online ahead of print.
Wetzel-Strong SE, Weinsheimer S, Nelson J, Pawlikowska L, Clark D, Starr MD, Liu Y, Kim H, Faughnan ME, Nixon AB, Marchuk DA. Pilot investigation of circulating angiogenic and inflammatory biomarkers associated with vascular malformations. Orphanet J Rare Dis. 2021 Sep 3;16(1):372. doi: 10.1186/s13023-021-02009-7.
Fox CK, Nelson J, McCulloch CE, Weinsheimer S, Pawlikowska L, Hart B, Mabray M, Zafar A, Morrison L, Zabramski JM, Akers A, Kim H. Seizure Incidence Rates in Children and Adults With Familial Cerebral Cavernous Malformations. Neurology. 2021 Aug 13;97(12):e1210-6. doi: 10.1212/WNL.0000000000012569. Online ahead of print.
Sabeti S, Ball KL, Bhattacharya SK, Bitrian E, Blieden LS, Brandt JD, Burkhart C, Chugani HT, Falchek SJ, Jain BG, Juhasz C, Loeb JA, Luat A, Pinto A, Segal E, Salvin J, Kelly KM. Consensus Statement for the Management and Treatment of Sturge-Weber Syndrome: Neurology, Neuroimaging, and Ophthalmology Recommendations. Pediatr Neurol. 2021 Aug;121:59-66. doi: 10.1016/j.pediatrneurol.2021.04.013. Epub 2021 May 6.
Keränen S, Suutarinen S, Mallick R, Laakkonen JP, Guo D, Pawlikowska L, Jahromi BR, Rauramaa T, Ylä-Herttuala S, Marchuk D, Krings T, Koivisto T, Lawton M, Radovanovic I, Kim H, Faughnan ME, Frösen J. Cyclo-oxygenase 2, a putative mediator of vessel remodeling, is expressed in the brain AVM vessels and associates with inflammation. Acta Neurochir (Wien). 2021 Sep;163(9):2503-2514. doi: 10.1007/s00701-021-04895-z. Epub 2021 Jun 29.
Mirza MH, Schwertner A, Kohlbrenner R, Dowd CF, Narsinh KH. Intracranial hemorrhage due to central venous occlusion from hemodialysis access: A case report. Interdiscip Neurosurg. 2021 Jun;24:101081. doi: 10.1016/j.inat.2020.101081. Epub 2021 Jan 4.
Narsinh KH, Caton MT, Mahmood NF, Higashida RT, Halbach VV, Hetts SW, Amans MR, Dowd CF, Cooke DL. Intrasaccular flow disruption (WEB) of a large wide-necked basilar apex aneurysm using PulseRider-assistance. Interdiscip Neurosurg. 2021 Jun;24:101072. doi: 10.1016/j.inat.2020.101072. Epub 2020 Dec 29.
Smegal LF, Sebold AJ, Hammill AM, Juhász C, Lo WD, Miles DK, Wilfong AA, Levin AV, Fisher B, Ball KL, Pinto AL, Comi AM; National Institutes of Health Sponsor: Rare Disease Clinical Research Consortium (RDCRN) Brain Vascular Malformation Consortium (BVMC) SWS Investigator Group. Multicenter Research Data of Epilepsy Management in Patients With Sturge-Weber Syndrome. Pediatr Neurol. 2021 Jun;119:3-10. doi: 10.1016/j.pediatrneurol.2021.02.006. Epub 2021 Mar 5.
Zhang Q, Wang C, Cannavicci A, Faughnan ME, Kutryk MJB. Endoglin deficiency impairs VEGFR2 but not FGFR1 or TIE2 activation and alters VEGF-mediated cellular responses in human primary endothelial cells. Transl Res. 2021 Sep;235:129-143. doi: 10.1016/j.trsl.2021.04.005. Epub 2021 Apr 22.
Narsinh KH, Kilbride BF, Mueller K, Murph D, Copelan A, Massachi J, Vitt J, Sun CH, Bhat H, Amans MR, Dowd CF, Halbach VV, Higashida RT, Moore T, Wilson MW, Cooke DL, Hetts SW. Combined Use of X-ray Angiography and Intraprocedural MRI Enables Tissue-based Decision Making Regarding Revascularization during Acute Ischemic Stroke Intervention. Radiology. 2021 Apr;299(1):167-176. doi: 10.1148/radiol.2021202750. Epub 2021 Feb 9.
Thorpe J, Frelin LP, McCann M, Pardo CA, Cohen BA, Comi AM, Pevsner J. Identification of a Mosaic Activating Mutation in GNA11 in Atypical Sturge-Weber Syndrome. J Invest Dermatol. 2021 Mar;141(3):685-688. doi: 10.1016/j.jid.2020.03.978. Epub 2020 Aug 7.
Sebold AJ, Day AM, Ewen J, Adamek J, Byars A, Cohen B, Kossoff EH, Mizuno T, Ryan M, Sievers J, Smegal L, Suskauer SJ, Thomas C, Vinks A, Zabel TA, Hammill AM, Comi AM. Sirolimus Treatment in Sturge-Weber Syndrome. Pediatr Neurol. 2021 Feb;115:29-40. doi: 10.1016/j.pediatrneurol.2020.10.013. Epub 2020 Nov 2.
Hart BL, Mabray MC, Morrison L, Whitehead KJ, Kim H. Systemic and CNS manifestations of inherited cerebrovascular malformations. Clin Imaging. 2021 Jul;75:55-66. doi: 10.1016/j.clinimag.2021.01.020. Epub 2021 Jan 20.
Thompson KP, Nelson J, Kim H, Pawlikowska L, Marchuk DA, Lawton MT, Faughnan ME; Brain Vascular Malformation Consortium HHT Investigator Group. Predictors of mortality in patients with hereditary hemorrhagic telangiectasia. Orphanet J Rare Dis. 2021 Jan 6;16(1):12. doi: 10.1186/s13023-020-01579-2.
Ross JM, Kim C, Allen D, Crouch EE, Narsinh K, Cooke DL, Abla AA, Nowakowski TJ, Winkler EA. The Expanding Cell Diversity of the Brain Vasculature. Front Physiol. 2020 Dec 3;11:600767. doi: 10.3389/fphys.2020.600767. eCollection 2020.
Narsinh KH, Mueller K, Nelson J, Massachi J, Murph DC, Copelan AZ, Hetts SW, Halbach VV, Higashida RT, Abla AA, Amans MR, Dowd CF, Kim H, Cooke DL. Interrater Reliability in the Measurement of Flow Characteristics on Color-Coded Quantitative DSA of Brain AVMs. AJNR Am J Neuroradiol. 2020 Dec;41(12):2303-2310. doi: 10.3174/ajnr.A6846. Epub 2020 Oct 29.
Copelan AZ, Smith ER, Drocton GT, Narsinh KH, Murph D, Khangura RS, Hartley ZJ, Abla AA, Dillon WP, Dowd CF, Higashida RT, Halbach VV, Hetts SW, Cooke DL, Keenan K, Nelson J, Mccoy D, Ciano M, Amans MR. Recent Administration of Iodinated Contrast Renders Core Infarct Estimation Inaccurate Using RAPID Software. AJNR Am J Neuroradiol. 2020 Dec;41(12):2235-2242. doi: 10.3174/ajnr.A6908. Epub 2020 Nov 19.
Isikbay M, Narsinh KH, Arroyo S, Smith WS, Cooke DL, Higashida RT, Amans MR. Computed tomography perfusion abnormalities after carotid endarterectomy help in the diagnosis of reversible cerebral vasoconstriction syndrome. J Vasc Surg Cases Innov Tech. 2020 Oct 27;7(1):171-175. doi: 10.1016/j.jvscit.2020.10.010. eCollection 2021 Mar.
Cannavicci A, Zhang Q, Kutryk MJB. Non-Coding RNAs and Hereditary Hemorrhagic Telangiectasia. J Clin Med. 2020 Oct 17;9(10):3333. doi: 10.3390/jcm9103333.
Copelan A, Drocton G, Caton MT, Smith ER, Cooke DL, Nelson J, Abla AA, Fox C, Amans MR, Dowd CF, Halbach VV, Higashida RT, Lawton MT, Kim H, Fullerton HJ, Gupta N, Hetts SW; UCSF Center For Cerebrovascular Research and UCSF Pediatric Brain Center. Brain Arteriovenous Malformation Recurrence After Apparent Microsurgical Cure: Increased Risk in Children Who Present With Arteriovenous Malformation Rupture. Stroke. 2020 Oct;51(10):2990-2996. doi: 10.1161/STROKEAHA.120.030135. Epub 2020 Sep 11.
Morshed RA, Abla AA, Murph D, Dao JM, Winkler EA, Burkhardt JK, Colao K, Hetts SW, Fullerton HJ, Lawton MT, Gupta N, Fox CK. Clinical outcomes after revascularization for pediatric moyamoya disease and syndrome: A single-center series. J Clin Neurosci. 2020 Sep;79:137-143. doi: 10.1016/j.jocn.2020.07.016. Epub 2020 Aug 19.
Kilian A, Latino GA, White AJ, Clark D, Chakinala MM, Ratjen F, McDonald J, Whitehead K, Gossage JR, Lin D, Henderson K, Pollak J, McWilliams JP, Kim H, Lawton MT, Faughnan ME; the Brain Vascular Malformation Consortium HHT Investigator Group. Genotype-Phenotype Correlations in Children with HHT. J Clin Med. 2020 Aug 22;9(9):2714. doi: 10.3390/jcm9092714.
Mabray MC, Caprihan A, Nelson J, McCulloch CE, Zafar A, Kim H, Hart BL, Morrison L. Effect of Simvastatin on Permeability in Cerebral Cavernous Malformation Type 1 Patients: Results from a Pilot Small Randomized Controlled Clinical Trial. Transl Stroke Res. 2020 Jun;11(3):319-321. doi: 10.1007/s12975-019-00737-4. Epub 2019 Oct 23.
Mabray MC, Starcevich J, Hallstrom J, Robinson M, Bartlett M, Nelson J, Zafar A, Kim H, Morrison L, Hart BL. High Prevalence of Spinal Cord Cavernous Malformations in the Familial Cerebral Cavernous Malformations Type 1 Cohort. AJNR Am J Neuroradiol. 2020 Jun;41(6):1126-1130. doi: 10.3174/ajnr.A6584. Epub 2020 May 28.
Polster SP, Sharma A, Tanes C, Tang AT, Mericko P, Cao Y, Carrión-Penagos J, Girard R, Koskimäki J, Zhang D, Stadnik A, Romanos SG, Lyne SB, Shenkar R, Yan K, Lee C, Akers A, Morrison L, Robinson M, Zafar A, Bittinger K, Kim H, Gilbert JA, Kahn ML, Shen L, Awad IA. Permissive microbiome characterizes human subjects with a neurovascular disease cavernous angioma. Nat Commun. 2020 May 27;11(1):2659. doi: 10.1038/s41467-020-16436-w.
Manole AK, Forrester VJ, Zlotoff BJ, Hart BL, Morrison LA. Cutaneous findings of familial cerebral cavernous malformation syndrome due to the common Hispanic mutation. Am J Med Genet A. 2020 May;182(5):1066-1072. doi: 10.1002/ajmg.a.61519. Epub 2020 Feb 26.
Campbell R, Petranovich CL, Cheek S, Morrison L, Hart B. Subjective Cognitive Concerns and Attitudes toward Genetic Testing Are Associated with Depressive Symptoms and Quality of Life after Genetic Testing for the Cerebral Cavernous Malformation Common Hispanic Mutation (CCM1). J Behav Brain Sci. 2020 Feb;10(2):118-127. doi: 10.4236/jbbs.2020.102007. Epub 2020 Feb 25.
Tandberg SR, Bocklage T, Bartlett MR, Morrison LA, Nelson J, Hart BL. Vertebral Intraosseous Vascular Malformations in a Familial Cerebral Cavernous Malformation Population: Prevalence, Histologic Features, and Associations With CNS Disease. AJR Am J Roentgenol. 2020 Feb;214(2):428-436. doi: 10.2214/AJR.19.21492. Epub 2019 Dec 11.
Choquet H, Kim H. Genome-wide Genotyping of Cerebral Cavernous Malformation Type 1 Individuals to Identify Genetic Modifiers of Disease Severity. Methods Mol Biol. 2020;2152:77-84. doi: 10.1007/978-1-0716-0640-7_6.
Shirali AS, Lluri G, Guihard PJ, Conrad MB, Kim H, Pawlikowska L, Boström KI, Iruela-Arispe ML, Aboulhosn JA. Angiopoietin-2 predicts morbidity in adults with Fontan physiology. Sci Rep. 2019 Dec 4;9(1):18328. doi: 10.1038/s41598-019-54776-w.
Harmon KA, Day AM, Hammill AM, Pinto AL, McCulloch CE, Comi AM; National Institutes of Health Rare Disease Clinical Research Consortium (RDCRN) Brain and Vascular Malformation Consortium (BVMC) SWS Investigator Group. Quality of Life in Children With Sturge-Weber Syndrome. Pediatr Neurol. 2019 Dec;101:26-32. doi: 10.1016/j.pediatrneurol.2019.04.004. Epub 2019 Apr 24.
Cho S, Maharathi B, Ball KL, Loeb JA, Pevsner J. Sturge-Weber Syndrome Patient Registry: Delayed Diagnosis and Poor Seizure Control. J Pediatr. 2019 Dec;215:158-163.e6. doi: 10.1016/j.jpeds.2019.08.025. Epub 2019 Oct 3.
Tang AT, Sullivan KR, Hong CC, Goddard LM, Mahadevan A, Ren A, Pardo H, Peiper A, Griffin E, Tanes C, Mattei LM, Yang J, Li L, Mericko-Ishizuka P, Shen L, Hobson N, Girard R, Lightle R, Moore T, Shenkar R, Polster SP, Roedel CJ, Li N, Zhu Q, Whitehead KJ, Zheng X, Akers A, Morrison L, Kim H, Bittinger K, Lengner CJ, Schwaninger M, Velcich A, Augenlicht L, Abdelilah-Seyfried S, Min W, Marchuk DA, Awad IA, Kahn ML. Distinct cellular roles for PDCD10 define a gut-brain axis in cerebral cavernous malformation. Sci Transl Med. 2019 Nov 27;11(520):eaaw3521. doi: 10.1126/scitranslmed.aaw3521.
Day AM, McCulloch CE, Hammill AM, Juhász C, Lo WD, Pinto AL, Miles DK, Fisher BJ, Ball KL, Wilfong AA, Levin AV, Thau AJ, Comi AM; National Institute of Health Sponsor: Rare Disease Clinical Research Consortium (RDCRN) Brain and Vascular Malformation Consortium (BVMC) SWS Investigator Group, Koenig JI, Lawton MT, Marchuk DA, Moses MA, Freedman SF, Pevsner J. Physical and Family History Variables Associated With Neurological and Cognitive Development in Sturge-Weber Syndrome. Pediatr Neurol. 2019 Jul;96:30-36. doi: 10.1016/j.pediatrneurol.2018.12.002. Epub 2018 Dec 20.
Cannavicci A, Zhang Q, Dai SC, Faughnan ME, Kutryk MJB. Decreased levels of miR-28-5p and miR-361-3p and increased levels of insulin-like growth factor 1 mRNA in mononuclear cells from patients with hereditary hemorrhagic telangiectasia (1). Can J Physiol Pharmacol. 2019 Jun;97(6):562-569. doi: 10.1139/cjpp-2018-0508. Epub 2018 Dec 4.
Zafar A, Quadri SA, Farooqui M, Ikram A, Robinson M, Hart BL, Mabray MC, Vigil C, Tang AT, Kahn ML, Yonas H, Lawton MT, Kim H, Morrison L. Familial Cerebral Cavernous Malformations. Stroke. 2019 May;50(5):1294-1301. doi: 10.1161/STROKEAHA.118.022314.
Wellman RJ, Cho SB, Singh P, Tune M, Pardo CA, Comi AM; BVMC Sturge–Weber syndrome Project Workgroup. Gαq and hyper-phosphorylated ERK expression in Sturge-Weber syndrome leptomeningeal blood vessel endothelial cells. Vasc Med. 2019 Feb;24(1):72-75. doi: 10.1177/1358863X18786068. Epub 2018 Aug 16.
Klostranec JM, Chen L, Mathur S, McDonald J, Faughnan ME, Ratjen F, Krings T. A theory for polymicrogyria and brain arteriovenous malformations in HHT. Neurology. 2019 Jan 1;92(1):34-42. doi: 10.1212/WNL.0000000000006686.
Day AM, Hammill AM, Juhász C, Pinto AL, Roach ES, McCulloch CE, Comi AM; National Institutes of Health Sponsor: Rare Diseases Clinical Research Network (RDCRN) Brain and Vascular Malformation Consortium (BVMC) SWS Investigator Group. Hypothesis: Presymptomatic treatment of Sturge-Weber Syndrome With Aspirin and Antiepileptic Drugs May Delay Seizure Onset. Pediatr Neurol. 2019 Jan;90:8-12. doi: 10.1016/j.pediatrneurol.2018.04.009. Epub 2018 Nov 24.
Morrison MA, Payabvash S, Chen Y, Avadiappan S, Shah M, Zou X, Hess CP, Lupo JM. A user-guided tool for semi-automated cerebral microbleed detection and volume segmentation: Evaluating vascular injury and data labelling for machine learning. Neuroimage Clin. 2018 Aug 4;20:498-505. doi: 10.1016/j.nicl.2018.08.002. eCollection 2018.
De la Torre AJ, Luat AF, Juhász C, Ho ML, Argersinger DP, Cavuoto KM, Enriquez-Algeciras M, Tikkanen S, North P, Burkhart CN, Chugani HT, Ball KL, Pinto AL, Loeb JA. A Multidisciplinary Consensus for Clinical Care and Research Needs for Sturge-Weber Syndrome. Pediatr Neurol. 2018 Jul;84:11-20. doi: 10.1016/j.pediatrneurol.2018.04.005. Epub 2018 Apr 18.
Pawlikowska L, Nelson J, Guo DE, McCulloch CE, Lawton MT, Kim H, Faughnan ME; Brain Vascular Malformation Consortium HHT Investigator Group. Association of common candidate variants with vascular malformations and intracranial hemorrhage in hereditary hemorrhagic telangiectasia. Mol Genet Genomic Med. 2018 May;6(3):350-356. doi: 10.1002/mgg3.377. Epub 2018 Mar 6.
Walcott BP, Winkler EA, Zhou S, Birk H, Guo D, Koch MJ, Stapleton CJ, Spiegelman D, Dionne-Laporte A, Dion PA, Kahle KT, Rouleau GA, Lawton MT. Identification of a rare BMP pathway mutation in a non-syndromic human brain arteriovenous malformation via exome sequencing. Hum Genome Var. 2018 Mar 8;5:18001. doi: 10.1038/hgv.2018.1. eCollection 2018.
Meybodi AT, Kim H, Nelson J, Hetts SW, Krings T, terBrugge KG, Faughnan ME, Lawton MT; Brain Vascular Malformation Consortium HHT Investigator Group. Surgical Treatment vs Nonsurgical Treatment for Brain Arteriovenous Malformations in Patients with Hereditary Hemorrhagic Telangiectasia: A Retrospective Multicenter Consortium Study. Neurosurgery. 2018 Jan 1;82(1):35-47. doi: 10.1093/neuros/nyx168.
Offermann EA, Sreenivasan A, DeJong MR, Lin DDM, McCulloch CE, Chung MG, Comi AM; National Institute of Health Sponsor; Rare Disease Clinical Research Consortium (RDCRN); Brain and Vascular Malformation Consortium (BVMC); National Sturge-Weber Syndrome Workgroup. Reliability and Clinical Correlation of Transcranial Doppler Ultrasound in Sturge-Weber Syndrome. Pediatr Neurol. 2017 Sep;74:15-23.e5. doi: 10.1016/j.pediatrneurol.2017.04.026. Epub 2017 May 8.
Dymerska M, Kirkorian AY, Offermann EA, Lin DD, Comi AM, Cohen BA. Size of Facial Port-Wine Birthmark May Predict Neurologic Outcome in Sturge-Weber Syndrome. J Pediatr. 2017 Sep;188:205-209.e1. doi: 10.1016/j.jpeds.2017.05.053. Epub 2017 Jul 12.
Strickland CD, Eberhardt SC, Bartlett MR, Nelson J, Kim H, Morrison LA, Hart BL. Familial Cerebral Cavernous Malformations Are Associated with Adrenal Calcifications on CT Scans: An Imaging Biomarker for a Hereditary Cerebrovascular Condition. Radiology. 2017 Aug;284(2):443-450. doi: 10.1148/radiol.2017161127. Epub 2017 Mar 20.
Zou X, Hart BL, Mabray M, Bartlett MR, Bian W, Nelson J, Morrison LA, McCulloch CE, Hess CP, Lupo JM, Kim H. Automated algorithm for counting microbleeds in patients with familial cerebral cavernous malformations. Neuroradiology. 2017 Jul;59(7):685-690. doi: 10.1007/s00234-017-1845-8. Epub 2017 May 22.
Kasthuri RS, Montifar M, Nelson J, Kim H, Lawton MT, Faughnan ME; Brain Vascular Malformation Consortium HHT Investigator Group. Prevalence and predictors of anemia in hereditary hemorrhagic telangiectasia. Am J Hematol. 2017 Jun 22:10.1002/ajh.24832. doi: 10.1002/ajh.24832. Online ahead of print.
Tang AT, Choi JP, Kotzin JJ, Yang Y, Hong CC, Hobson N, Girard R, Zeineddine HA, Lightle R, Moore T, Cao Y, Shenkar R, Chen M, Mericko P, Yang J, Li L, Tanes C, Kobuley D, Võsa U, Whitehead KJ, Li DY, Franke L, Hart B, Schwaninger M, Henao-Mejia J, Morrison L, Kim H, Awad IA, Zheng X, Kahn ML. Endothelial TLR4 and the microbiome drive cerebral cavernous malformations. Nature. 2017 May 18;545(7654):305-310. doi: 10.1038/nature22075. Epub 2017 May 10.
Lo WD, Kumar R. Arterial Ischemic Stroke in Children and Young Adults. Continuum (Minneap Minn). 2017 Feb;23(1, Cerebrovascular Disease):158-180. doi: 10.1212/CON.0000000000000438.
Pilli VK, Chugani HT, Juhász C. Enlargement of deep medullary veins during the early clinical course of Sturge-Weber syndrome. Neurology. 2017 Jan 3;88(1):103-105. doi: 10.1212/WNL.0000000000003455. Epub 2016 Nov 18.
Walcott BP, Choudhri O, Lawton MT. Brainstem cavernous malformations: Natural history versus surgical management. J Clin Neurosci. 2016 Oct;32:164-5. doi: 10.1016/j.jocn.2016.03.021. Epub 2016 Jun 16.
Walcott BP, Winkler EA, Rouleau GA, Lawton MT. Molecular, Cellular, and Genetic Determinants of Sporadic Brain Arteriovenous Malformations. Neurosurgery. 2016 Aug;63 Suppl 1(Suppl 1 CLINICAL NEUROSURGERY):37-42. doi: 10.1227/NEU.0000000000001300.
Walcott BP, Reinshagen C, Stapleton CJ, Choudhri O, Rayz V, Saloner D, Lawton MT. Predictive modeling and in vivo assessment of cerebral blood flow in the management of complex cerebral aneurysms. J Cereb Blood Flow Metab. 2016 Jun;36(6):998-1003. doi: 10.1177/0271678X16641125. Epub 2016 Mar 23.
Merkel PA, Manion M, Gopal-Srivastava R, Groft S, Jinnah HA, Robertson D, Krischer JP; Rare Diseases Clinical Research Network. The partnership of patient advocacy groups and clinical investigators in the rare diseases clinical research network. Orphanet J Rare Dis. 2016 May 18;11(1):66. doi: 10.1186/s13023-016-0445-8.
Kaplan EH, Kossoff EH, Bachur CD, Gholston M, Hahn J, Widlus M, Comi AM. Anticonvulsant Efficacy in Sturge-Weber Syndrome. Pediatr Neurol. 2016 May;58:31-6. doi: 10.1016/j.pediatrneurol.2015.10.015. Epub 2016 Jan 11.
Comi AM, Sahin M, Hammill A, Kaplan EH, Juhász C, North P, Ball KL, Levin AV, Cohen B, Morris J, Lo W, Roach ES; 2015 Sturge-Weber Syndrome Research Workshop. Leveraging a Sturge-Weber Gene Discovery: An Agenda for Future Research. Pediatr Neurol. 2016 May;58:12-24. doi: 10.1016/j.pediatrneurol.2015.11.009. Epub 2016 Mar 16.
Choquet H, Trapani E, Goitre L, Trabalzini L, Akers A, Fontanella M, Hart BL, Morrison LA, Pawlikowska L, Kim H, Retta SF. Cytochrome P450 and matrix metalloproteinase genetic modifiers of disease severity in Cerebral Cavernous Malformation type 1. Free Radic Biol Med. 2016 Mar;92:100-109. doi: 10.1016/j.freeradbiomed.2016.01.008. Epub 2016 Jan 19.
Kavanaugh B, Sreenivasan A, Bachur C, Papazoglou A, Comi A, Zabel TA. [Formula: see text]Intellectual and adaptive functioning in Sturge-Weber Syndrome. Child Neuropsychol. 2016;22(6):635-48. doi: 10.1080/09297049.2015.1028349. Epub 2015 May 8.
Comi A. Current Therapeutic Options in Sturge-Weber Syndrome. Semin Pediatr Neurol. 2015 Dec;22(4):295-301. doi: 10.1016/j.spen.2015.10.005. Epub 2015 Nov 11.
Choquet H, Pawlikowska L, Lawton MT, Kim H. Genetics of cerebral cavernous malformations: current status and future prospects. J Neurosurg Sci. 2015 Sep;59(3):211-20. Epub 2015 Apr 22.
Hart BL, Ketai L. Armies of pestilence: CNS infections as potential weapons of mass destruction. AJNR Am J Neuroradiol. 2015 Jun;36(6):1018-25. doi: 10.3174/ajnr.A4177. Epub 2014 Dec 4.
Pawlikowska L, Nelson J, Guo DE, McCulloch CE, Lawton MT, Young WL, Kim H, Faughnan ME; Brain Vascular Malformation Consortium HHT Investigator Group. The ACVRL1 c.314-35A>G polymorphism is associated with organ vascular malformations in hereditary hemorrhagic telangiectasia patients with ENG mutations, but not in patients with ACVRL1 mutations. Am J Med Genet A. 2015 Jun;167(6):1262-7. doi: 10.1002/ajmg.a.36936. Epub 2015 Apr 2.
Kim H, Nelson J, Krings T, terBrugge KG, McCulloch CE, Lawton MT, Young WL, Faughnan ME; Brain Vascular Malformation Consortium HHT Investigator Group. Hemorrhage rates from brain arteriovenous malformation in patients with hereditary hemorrhagic telangiectasia. Stroke. 2015 May;46(5):1362-4. doi: 10.1161/STROKEAHA.114.007367. Epub 2015 Apr 9.
Golden MJ, Morrison LA, Kim H, Hart BL. Increased number of white matter lesions in patients with familial cerebral cavernous malformations. AJNR Am J Neuroradiol. 2015 May;36(5):899-903. doi: 10.3174/ajnr.A4200. Epub 2015 Jan 2.
Krings T, Kim H, Power S, Nelson J, Faughnan ME, Young WL, terBrugge KG; Brain Vascular Malformation Consortium HHT Investigator Group. Neurovascular manifestations in hereditary hemorrhagic telangiectasia: imaging features and genotype-phenotype correlations. AJNR Am J Neuroradiol. 2015 May;36(5):863-70. doi: 10.3174/ajnr.A4210. Epub 2015 Jan 8.
Golden M, Saeidi S, Liem B, Marchand E, Morrison L, Hart B. Sensitivity of patients with familial cerebral cavernous malformations to therapeutic radiation. J Med Imaging Radiat Oncol. 2015 Feb;59(1):134-6. doi: 10.1111/1754-9485.12269. Epub 2015 Jan 7.
Comi AM. Sturge-Weber syndrome. Handb Clin Neurol. 2015;132:157-68. doi: 10.1016/B978-0-444-62702-5.00011-1.
Latino GA, Kim H, Nelson J, Pawlikowska L, Young W, Faughnan ME; Brain Vascular Malformation Consortium HHT Investigator Group. Severity score for hereditary hemorrhagic telangiectasia. Orphanet J Rare Dis. 2014 Dec 29;9:188. doi: 10.1186/s13023-014-0188-3.
Reidy TG, Suskauer SJ, Bachur CD, McCulloch CE, Comi AM. Preliminary reliability and validity of a battery for assessing functional skills in children with Sturge-Weber syndrome. Childs Nerv Syst. 2014 Dec;30(12):2027-36. doi: 10.1007/s00381-014-2573-6. Epub 2014 Oct 26.
Lance EI, Lanier KE, Zabel TA, Comi AM. Stimulant use in patients with sturge-weber syndrome: safety and efficacy. Pediatr Neurol. 2014 Nov;51(5):675-80. doi: 10.1016/j.pediatrneurol.2013.11.009. Epub 2013 Nov 21.
Cheng KH, Mariampillai A, Lee KK, Vuong B, Luk TW, Ramjist J, Curtis A, Jakubovic H, Kertes P, Letarte M, Faughnan ME; Brain Vascular Malformation Consortium HHT Investigator Group, Yang VX. Histogram flow mapping with optical coherence tomography for in vivo skin angiography of hereditary hemorrhagic telangiectasia. J Biomed Opt. 2014 Aug;19(8):086015. doi: 10.1117/1.JBO.19.8.086015.
Choquet H, Nelson J, Pawlikowska L, McCulloch CE, Akers A, Baca B, Khan Y, Hart B, Morrison L, Kim H. Association of cardiovascular risk factors with disease severity in cerebral cavernous malformation type 1 subjects with the common Hispanic mutation. Cerebrovasc Dis. 2014;37(1):57-63. doi: 10.1159/000356839. Epub 2013 Dec 21.
Choquet H, Pawlikowska L, Nelson J, McCulloch CE, Akers A, Baca B, Khan Y, Hart B, Morrison L, Kim H; Brain Vascular Malformation Consortium (BVMC) Study. Polymorphisms in inflammatory and immune response genes associated with cerebral cavernous malformation type 1 severity. Cerebrovasc Dis. 2014;38(6):433-40. doi: 10.1159/000369200. Epub 2014 Dec 3.
Hart BL, Taheri S, Rosenberg GA, Morrison LA. Dynamic contrast-enhanced MRI evaluation of cerebral cavernous malformations. Transl Stroke Res. 2013 Oct;4(5):500-6. doi: 10.1007/s12975-013-0285-y. Epub 2013 Sep 21.
Bachur CD, Comi AM. Sturge-weber syndrome. Curr Treat Options Neurol. 2013 Oct;15(5):607-17. doi: 10.1007/s11940-013-0253-6.
Arora KS, Quigley HA, Comi AM, Miller RB, Jampel HD. Increased choroidal thickness in patients with Sturge-Weber syndrome. JAMA Ophthalmol. 2013 Sep;131(9):1216-9. doi: 10.1001/jamaophthalmol.2013.4044.
Sreenivasan AK, Bachur CD, Lanier KE, Curatolo AS, Connors SM, Moses MA, Comi AM. Urine vascular biomarkers in Sturge-Weber syndrome. Vasc Med. 2013 Jun;18(3):122-8. doi: 10.1177/1358863X13486312.
Shirley MD, Tang H, Gallione CJ, Baugher JD, Frelin LP, Cohen B, North PE, Marchuk DA, Comi AM, Pevsner J. Sturge-Weber syndrome and port-wine stains caused by somatic mutation in GNAQ. N Engl J Med. 2013 May 23;368(21):1971-9. doi: 10.1056/NEJMoa1213507. Epub 2013 May 8.
Lopez J, Yeom KW, Comi A, Van Haren K. Case report of subdural hematoma in a patient with Sturge-Weber syndrome and literature review: questions and implications for therapy. J Child Neurol. 2013 May;28(5):672-5. doi: 10.1177/0883073812449514. Epub 2012 Jul 17.
Akers AL, Ball KL, Clancy M, Comi AM, Faughnan ME, Gopal-Srivastava R, Jacobs TP, Kim H, Krischer J, Marchuk DA, McCulloch CE, Morrison L, Moses M, Moy CS, Pawlikowska L, Young WL. Brain Vascular Malformation Consortium: Overview, Progress and Future Directions. J Rare Disord. 2013 Apr 1;1(1):5.
Lance EI, Sreenivasan AK, Zabel TA, Kossoff EH, Comi AM. Aspirin use in Sturge-Weber syndrome: side effects and clinical outcomes. J Child Neurol. 2013 Feb;28(2):213-8. doi: 10.1177/0883073812463607. Epub 2012 Oct 30.
Siddique L, Sreenivasan A, Comi AM, Germain-Lee EL. Importance of utilizing a sensitive free thyroxine assay in Sturge-Weber syndrome. J Child Neurol. 2013 Feb;28(2):269-74. doi: 10.1177/0883073812463606. Epub 2012 Oct 30.
Nishida T, Faughnan ME, Krings T, Chakinala M, Gossage JR, Young WL, Kim H, Pourmohamad T, Henderson KJ, Schrum SD, James M, Quinnine N, Bharatha A, Terbrugge KG, White RI Jr. Brain arteriovenous malformations associated with hereditary hemorrhagic telangiectasia: gene-phenotype correlations. Am J Med Genet A. 2012 Nov;158A(11):2829-34. doi: 10.1002/ajmg.a.35622. Epub 2012 Sep 18.
Lo W, Marchuk DA, Ball KL, Juhász C, Jordan LC, Ewen JB, Comi A; Brain Vascular Malformation Consortium National Sturge-Weber Syndrome Workgroup. Updates and future horizons on the understanding, diagnosis, and treatment of Sturge-Weber syndrome brain involvement. Dev Med Child Neurol. 2012 Mar;54(3):214-23. doi: 10.1111/j.1469-8749.2011.04169.x. Epub 2011 Dec 23.
Bharatha A, Faughnan ME, Kim H, Pourmohamad T, Krings T, Bayrak-Toydemir P, Pawlikowska L, McCulloch CE, Lawton MT, Dowd CF, Young WL, Terbrugge KG. Brain arteriovenous malformation multiplicity predicts the diagnosis of hereditary hemorrhagic telangiectasia: quantitative assessment. Stroke. 2012 Jan;43(1):72-8. doi: 10.1161/STROKEAHA.111.629865. Epub 2011 Oct 27.
Comi AM. Presentation, diagnosis, pathophysiology, and treatment of the neurological features of Sturge-Weber syndrome. Neurologist. 2011 Jul;17(4):179-84. doi: 10.1097/NRL.0b013e318220c5b6.
Petersen TA, Morrison LA, Schrader RM, Hart BL. Familial versus sporadic cavernous malformations: differences in developmental venous anomaly association and lesion phenotype. AJNR Am J Neuroradiol. 2010 Feb;31(2):377-82. doi: 10.3174/ajnr.A1822. Epub 2009 Oct 15.
Colombo GM, Wiese AD, Mercado AE, Shepherd WS, Fynan M, Ayers K, Rork WC, Kostick-Quenet KM, Nguyen D, Schneider SC, Morales JM, Kazimi SI, Cho HE, Members Of The Bbdc, Murali CN, Robinson ME, Lee B, Sutton VR, Storch EA. Osteogenesis imperfecta and the family: A qualitative analysis of the experiences of family and caregivers. Fam Syst Health. 2025 Jul 10:10.1037/fsh0001004. doi: 10.1037/fsh0001004. Epub ahead of print. PMID: 40638332; PMCID: PMC12252216.
Osteogenesis imperfecta (OI) is a group of inherited connective tissue disorders associated with a wide range of symptoms, including fragile bones that break easily. Not much is known about the psychosocial impact of OI during childhood on caregivers and families.
In this study, researchers explored caregiver experiences, existing social support provided for families affected by OI, and the impact of OI on family life. The team analyzed survey responses from 13 caregivers of individuals with OI to develop themes on the psychosocial impact of OI on the family unit.
Results revealed four themes, including encountering difficult experiences during diagnosis of OI, caregiver well-being and coping, broad family impact, and the existence and further need for social support. Authors note that these findings have implications for child and caregiver well-being and health care professionals during diagnosis, as well as emphasize the need for social support for families affected by OI.
Folkestad L, Prakash SK, Nagamani SCS, Andersen NH, Carter E, Hald JD, Johnson RJ, Langdahl B, Perfetto EM, Raggio C, Ralston SH, Sandhaus RA, Semler O, Tosi L, Orwoll E. Cardiovascular disease in adults with osteogenesis imperfecta: clinical characteristics, care recommendations, and research priorities identified using a modified Delphi technique. J Bone Miner Res. 2025 Feb 2;40(2):211-221. doi: 10.1093/jbmr/zjae197.
Nicol LE, Baines H, Koike S, Liu W. Cross-sectional and longitudinal analysis of bone age maturation during peri-pubertal growth in children with type I, III and IV osteogenesis imperfecta. Bone. 2024 Oct;187:117192. doi: 10.1016/j.bone.2024.117192. Epub 2024 Jul 4. PMID: 38969279; PMCID: PMC11324408.
Osteogenesis imperfecta (OI) is a group of inherited connective tissue disorders associated with a wide range of symptoms, including fragile bones that break easily. In typically developing children, radiographic images can reveal predictable patterns of changes in the size, shape, and mineralization of the hand and wrist bones. Known as the bone age, this metric can be used to assess time remaining for growth as well as the onset and duration of puberty, helping to determine the timing of surgeries or reveal deviations in a child’s growth pattern.
In this study, researchers explored bone age maturation during adolescent growth in patients with OI. The team compared radiographs of the hand and wrist in 159 children with OI ages 8 to 17 with healthy controls. Bone ages were repeated around two years later and analyzed by both an endocrinologist and automated program called BoneXpert.
Results showed that in children with mild-to-moderate OI (types I and IV), skeletal maturation is comparable to healthy controls. For those with more severe forms of OI (type III), results showed a delayed pattern of skeletal maturation of less than a year at baseline and a delayed rate of maturation over the two-year follow-up. However, authors note that these differences may not be clinically significant, concluding that bone age can be used in the OI population in a way that is similar to the general pediatric population.
Marulanda J, Retrouvey JM, Lee B, Sutton VR; Members of the BBDC; Rauch F, Briner M. Cranio-cervical abnormalities in moderate-to-severe osteogenesis imperfecta - Genotypic and phenotypic determinants. Orthod Craniofac Res. 2024 Apr;27(2):237-243. doi: 10.1111/ocr.12707. Epub 2023 Aug 29.
Marom R, Song IW, Busse EC, Washington ME, Berrier AS, Rossi VC, Ortinau L, Jeong Y, Jiang MM, Dawson BC, Adeyeye M, Leynes C, Lietman CD, Stroup BM, Batkovskyte D, Jain M, Chen Y, Cela R, Castellon A, Tran AA, Lorenzo I, Meyers DN, Huang S, Turner A, Shenava V, Wallace M, Orwoll E, Park D, Ambrose CG, Nagamani SC, Heaney JD, Lee BH. The IFITM5 mutation in osteogenesis imperfecta type V is associated with an ERK/SOX9-dependent osteoprogenitor differentiation defect. J Clin Invest. 2024 Jun 17;134(15):e170369. doi: 10.1172/JCI170369.
Cho HE, Shepherd WS, Colombo GM, Wiese AD, Rork WC, Kostick KM, Nguyen D; Members of the BBDC; Murali CN, Robinson ME, Schneider SC, Qian JH, Lee B, Sutton VR, Storch EA. Resilience and coping: a qualitative analysis of cognitive and behavioral factors in adults with osteogenesis Imperfecta. Disabil Rehabil. 2024 Jun 6:1-10. doi: 10.1080/09638288.2024.2358903. Online ahead of print.
Hald JD, Langdahl B, Folkestad L, Wekre LL, Johnson R, Nagamani SCS, Raggio C, Ralston SH, Semler O, Tosi L, Orwoll E. Osteogenesis Imperfecta: Skeletal and Non-skeletal Challenges in Adulthood. Calcif Tissue Int. 2024 Jun 5. doi: 10.1007/s00223-024-01236-x. Online ahead of print.
Busse E, Lee B, Nagamani SCS. Genetic Evaluation for Monogenic Disorders of Low Bone Mass and Increased Bone Fragility: What Clinicians Need to Know. Curr Osteoporos Rep. 2024 Apr 11. doi: 10.1007/s11914-024-00870-6. Epub ahead of print. PMID: 38600318.
Monogenic disorders of osteoporosis are characterized by low bone mass, increased bone fragility, and increased risk of fractures. There are currently over 50 different known types of these disorders, which are each caused by variations in a single gene. Widespread availability of clinical genetic testing offers an opportunity to correctly diagnose individuals with these disorders.
In this review paper, researchers discuss genetic testing for patients with suspected monogenic forms of osteoporosis. The team outlines the principles of clinical genetic testing and provides practical guidance for clinicians to navigate the process.
Authors note that clinicians should be aware of how to incorporate genetic testing into their practices, as these techniques could help identify the appropriate diagnosis for patients with low bone mass, multiple or unusual fractures, and severe or early-onset osteoporosis.
Liu W, Nicol L, Orwoll E. Current and Developing Pharmacologic Agents for Improving Skeletal Health in Adults with Osteogenesis Imperfecta. Calcif Tissue Int. 2024 Mar 12. doi: 10.1007/s00223-024-01188-2. Epub ahead of print. PMID: 38472351.
Osteogenesis imperfecta (OI) is a group of inherited connective tissue disorders associated with a wide range of symptoms, including fragile bones that break easily. Drugs to improve skeletal health—including those initially developed to treat osteoporosis as well as new bone-protective agents—are in various phases of clinical trials for adults with OI.
In this review article, researchers summarize current and developing pharmacologic agents for improving skeletal health in adults with OI. The team performed online database searches to review published studies and clinical trials.
Results include ongoing clinical trials for several therapeutics, including those that may be useful in improving bone mineral density. Authors note that clinical trials involving gene editing may be possible in the coming decade.
Rork WC, Hertz AG, Wiese AD, Kostick KM, Nguyen D, Schneider SC, Shepherd WS, Cho H; Members of the BBDC; Murali CN, Lee B, Sutton VR, Storch EA. A qualitative exploration of patient perspectives on psychosocial burdens and positive factors in adults with osteogenesis imperfecta. Am J Med Genet A. 2023 Sep;191(9):2267-2275. doi: 10.1002/ajmg.a.63323. Epub 2023 Jun 15. PMID: 37317786
Osteogenesis imperfecta (OI) is a group of inherited connective tissue disorders associated with a wide range of symptoms, including fragile bones that break easily. Although progress has been made in understanding the spectrum of physical symptoms, less is known about the impact of OI on psychosocial well-being, as well as factors that can help lessen negative outcomes.
In this study, researchers developed a qualitative approach to assess perspectives from individuals with OI on psychosocial burdens and positive factors related to OI. Among 15 adults with varying disease status, the team conducted semi-structured interviews and identified themes from responses.
Participants reported negative psychosocial outcomes related to bone fractures and recovery, uncertainty of future fractures, and self-image. Participants also described positive traits related to OI and their lived experience with a chronic disease. Authors note that these insights highlight a need for continued research on the relationship between OI disease status and psychosocial outcomes, as well as the development of psychological interventions designed for individuals with OI.
Liu W, Lee B, Nagamani SCS, Nicol L, Rauch F, Rush ET, Sutton VR, Orwoll E. Approach to the Patient: Pharmacological therapies for fracture risk reduction in adults with osteogenesis imperfecta. J Clin Endocrinol Metab. 2023 Jan 20:dgad035. doi: 10.1210/clinem/dgad035. Epub ahead of print. PMID: 36658750.
Osteogenesis imperfecta (OI) is a group of 21 rare, inherited disorders caused by 19 gene mutations resulting in fragile bones that break easily. The effectiveness of medications used for fracture reduction in adults with OI, as well as practice recommendations, are not well established.
In this review paper, researchers summarize current knowledge on pharmacologic treatment options for reducing fracture risk in adults with OI. In addition to manual searches of reference lists, the team performed a PubMed online database search of all study types published in the English language using the terms “osteogenesis imperfecta,” “OI,” and “brittle bone disease.”
Findings show that despite limited clinical trial data, bisphosphonate and teriparatide therapies may help improve bone mineral density in adults with OI. Authors state that further research is needed to develop medications for adults with OI that will lead to definite fracture rate reduction.
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While people with motor neuron disease (MND) experience cognitive and behavioral dysfunction, the onset and progression of these symptoms, relative to motor manifestations, remains unclear. In this study, CReATe Consortium researchers explored changes in these deficits over time, and whether demographic, clinical, or genetic factors affected these symptoms.
A total of 237 participants were recruited through the consortium’s Phenotype-Genotype-Biomarker study. The Edinburgh Cognitive and Behavioural Amyotrophic Lateral Sclerosis Screen was administered every three to six months to assess ALS-specific cognitive issues, such as executive function, verbal fluency, and language; and ALS non-specific memory and visuospatial functions. Behavioral symptoms like apathy, disinhibition, loss of sympathy and perseveration and hyperorality, were reported through semi-structured interviews.
In this large observational study, cognitive impairment at initial assessment was infrequent, but when present, most often involved language and executive functions. These impairments were associated with lower educational levels, but not with the C9ORF72 repeat expansion. We also found that cognition remained stable over time for most patients. However, a small subset showed decline on all cognitive domains, which was not entirely explained by the presence of a C9ORF72 repeat expansion. Behavioral symptoms in these MND participants were uncommon.
Our findings raise questions about the timing of cognitive impairment in MND, and whether it arises during early clinically manifest disease or even prior to motor manifestations. This highlights the need for future research to identify when these cognitive symptoms begin and what other factors are associated with decline over time.
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Amyotrophic lateral sclerosis (ALS) patients experience a wide variety of physical, mental, emotional, and social symptoms of the disease. Tools to track a patient’s subtle but important changes over time are important for managing the disease burden as well as assessing promising new therapeutic agents. Therefore, highly reliable, sensitive, and valid disease-specific outcome measures for ALS are vital for clinicians and researchers, as well as patients and family members.
In this study, the authors report the development of the Amyotrophic Lateral Sclerosis-Health Index (ALS-HI), which was created and validated in accordance with FDA guidance. This is a multifactorial, disease-specific patient-reported outcome measure capable of measuring meaningful changes in how an ALS patient feels and functions.
To develop the ALS-HI, the authors surveyed a national cross section of 497 individuals with ALS. After identifying the most important symptoms of ALS, they performed factor analysis, qualitative patient interviews, test-retest reliability assessment, and known groups analysis to evaluate and validate the ALS-HI. Fifteen participants took part in a beta test and found the ALS-HI to be clear, easy to use, and relevant.
The study supports use of the ALS-HI as a valid, sensitive, and reliable instrument to assess the disease burden of individual patients with ALS. The ALS-HI could also serve as an effective mechanism to track disease progression and treatment efficacy during therapeutic trials.
Mahungu AC, Steyn E, Floudiotis N, Wilson LA, Vandrovcova J, Reilly MM, Record CJ, Benatar M, Wu G, Raga S, Wilmshurst JM, Naidu K, Hanna M, Nel M, Heckmann JM. The mutational profile in a South African cohort with inherited neuropathies and spastic paraplegia. Front Neurol. 2023 Aug 29;14:1239725. doi: 10.3389/fneur.2023.1239725. eCollection 2023.
Zizzi C, Seabury J, Rosero S, Alexandrou D, Wagner E, Weinstein JS, Varma A, Dilek N, Heatwole J, Wuu J, Caress J, Bedlack R, Granit V, Statland JM, Mehta P, Benatar M, Heatwole C. Patient reported impact of symptoms in amyotrophic lateral sclerosis (PRISM-ALS): A national, cross-sectional study. EClinicalMedicine. 2022 Dec 13;55:101768. doi: 10.1016/j.eclinm.2022.101768. PMID: 36531982; PMCID: PMC9755057.
Kessler C, Ruschil C, Abdelhak A, Wilke C, Maleska A, Kuhle J, Krumbholz M, Kowarik MC, Schüle R. Serum. Neurofilament Light Chain and Glial Fibrillary Acidic Protein as Biomarkers in Primary Progressive Multiple Sclerosis and Hereditary Spastic Paraplegia Type 4. Int J Mol Sci. 2022 Nov 3;23(21):13466. doi: 10.3390/ijms232113466. PMID: 36362248; PMCID: PMC9657281.
Primary progressive multiple sclerosis (PPMS) and hereditary spastic paraplegia (HSP) are inherited disorders affecting nerves that send messages to the muscles. Because patients with both disorders can present with slowly progressive spastic paraparesis (weakness in the legs), accurate diagnoses are often challenging. In this study, researchers investigated the use of serum neurofilament light chain (sNfL) and glial fibrillary acidic protein (sGFAP) as biomarkers to support diagnosis. The team assessed sNfl and sGFAP levels in 25 patients with PPMS, 25 patients with spastic paraplegia type 4 (SPG4, the most common type of HSP), and 60 control subjects. Results showed that sNfl levels were significantly higher in patients with PPMS compared to patients with SPG4. Researchers also observed a trend toward relatively higher sGFAP levels in patients with PPMS. However, because both groups of patients showed overlapping biomarker values, the team did not find sNfL and sGFAP to be useful biomarkers. As findings indicate that sNfL and sGFAP are most significantly elevated in the early disease stages of PPMS, authors note that further investigation is warranted.
Albertyn CH, Hardy A, Bakker LA, Hlangani M, Van Der Walt K, Zeilinga B, Thomas KGF, Heckmann JM. Adaptation and norming of the Edinburgh Cognitive and behavioural amyotrophic lateral sclerosis screen (ECAS) for three language groups in South Africa. Amyotroph Lateral Scler Frontotemporal Degener. 2022 Nov;23(7-8):532-541. doi: 10.1080/21678421.2022.2030361. Epub 2022 Feb 4.
Benatar M, Wuu J, Turner MR. Neurofilament light chain in drug development for amyotrophic lateral sclerosis: a critical appraisal. Brain. 2022 Oct 31:awac394. doi: 10.1093/brain/awac394. Epub ahead of print. PMID: 36310538.
Interest in amyotrophic lateral sclerosis (ALS) biomarkers has grown exponentially over the course of the last 25 years, with great hope that they might serve as tools to facilitate the development of meaningful therapies for this otherwise progressive and fatal disease. Effective use of biomarkers, however, requires an understanding of what it means for them to be “fit-for-purpose,” as well as an appreciation of the nuances of the clinical contexts in which they will be applied. Neurofilament light chain (NfL) has emerged as a leading candidate with enormous potential to aid ALS therapy development. However, Nfl is also profoundly misunderstood. Within the conceptual framework of the BEST (Biomarkers, EndpointS, and other Tools) Resource developed by the National Institutes of Health and the Food & Drug Administration in the United States, authors consider the evidence supporting the use of NfL for a variety of purposes in different clinical contexts. Authors conclude that NfL may serve as a susceptibility/risk biomarker in populations at elevated risk for ALS, and that NfL has value as a prognostic biomarker when measured early in the course of established disease. Authors also conclude that NfL may serve as a pharmacodynamic biomarker, as a reduction in NfL in response to an experimental therapeutic might aid go/no-go decisions in phase 2 clinical trials. A reduction in NfL may also be a reasonably likely surrogate endpoint for experimental therapeutics administered early in the course of disease.
Benatar M, Granit V, Andersen PM, Grignon AL, McHutchison C, Cosentino S, Malaspina A, Wuu J. Mild motor impairment as prodromal state in amyotrophic lateral sclerosis: a new diagnostic entity. Brain. 2022 May 20:awac185. doi: 10.1093/brain/awac185. Epub ahead of print. PMID: 35594156.
Chen W, Wang S, Tithi SS, Ellison DW, Schaid DJ, Wu G. A rare variant analysis framework using public genotype summary counts to prioritize disease-predisposition genes. Nat Commun. 2022 May 11;13(1):2592. doi: 10.1038/s41467-022-30248-0.
Wang TW, Wuu J, Cooley A, Yeh TS, Benatar M, Weisskopf M. Occupational lead exposure and survival with amyotrophic lateral sclerosis. Amyotroph Lateral Scler Frontotemporal Degener. 2022 Apr 9;1-8. doi: 10.1080/21678421.2022.2059379. Online ahead of print.
McMillan CT, Wuu J, Rascovsky K, Cosentino S, Grossman M, Elman L, Quinn C, Rosario L, Stark JH, Granit V, Briemberg H, Chenji S, Dionne A, Genge A, Johnston W, Korngut L, Shoesmith C, Zinman L; Canadian ALS Neuroimaging Consortium (CALSNIC), Kalra S, Benatar M. Defining cognitive impairment in amyotrophic lateral sclerosis: an evaluation of empirical approaches. Amyotroph Lateral Scler Frontotemporal Degener. 2022 Mar 7:1-10. doi: 10.1080/21678421.2022.2039713. Online ahead of print.
Kessler C, Serna-Higuita LM, Wilke C, Rattay TW, Hengel H, Reichbauer J, Stransky E, Leyva-Gutiérrez A, Mengel D, Synofzik M, Schöls L, Martus P, Schüle R. Characteristics of serum neurofilament light chain as a biomarker in hereditary spastic paraplegia type 4. Ann Clin Transl Neurol.. 2022 Mar;9(3):326-338. doi: 10.1002/acn3.51518. Epub 2022 Feb 16. PMID: 35171517; PMCID: PMC8935322.
Benatar M, Wuu J, McHutchison C, Postuma RB, Boeve BF, Petersen R, Ross CA, Rosen H, Arias JJ, Fradette S, McDermott MP, Shefner J, Stanislaw C, Abrahams S, Cosentino S, Andersen PM, Finkel RS, Granit V, Grignon AL, Rohrer JD, McMillan CT, Grossman M, Al-Chalabi A, Turner MR; First International Pre-Symptomatic ALS Workshop. Preventing amyotrophic lateral sclerosis: insights from pre-symptomatic neurodegenerative diseases. Brain. 2022 Mar 29;145(1):27-44. doi: 10.1093/brain/awab404. PMID: 34677606; PMCID: PMC8967095.
Phillips JS, Nitchie FJ 4th, Da Re F, Olm CA, Cook PA, McMillan CT, Irwin DJ, Gee JC, Dubroff JG, Grossman M, Nasrallah IM; Alzheimer's Disease Neuroimaging Initiative. Rates of longitudinal change in (18) F-flortaucipir PET vary by brain region, cognitive impairment, and age in atypical Alzheimer's disease. Alzheimers Dement. 2022 Jun;18(6):1235-1247. doi: 10.1002/alz.12456. Epub 2021 Sep 13.
Nel M, Mahungu AC, Monnakgotla N, Botha GR, Mulder NJ, Wu G, Rampersaud E, van Blitterswijk M, Wuu J, Cooley A, Myers J, Rademakers R, Taylor JP, Benatar M, Heckmann JM. Revealing the Mutational Spectrum in Southern Africans with Amyotrophic Lateral Sclerosis. Neurol Genet. 2022 Jan 12;8(1):e654. doi: 10.1212/NXG.0000000000000654. PMID: 35047667; PMCID: PMC8756565.
Melina Ramic, Nadja S Andrade, Matthew J Rybin, Rustam Esanov, Claes Wahlestedt, Michael Benatar, Zane Zeier. Epigenetic small moleculars rescue nucleocytoplasmic transport and DNA damage phenotypes in C9ORF72 ALS/FTD. . 2021 Nov 20;11(11):1543. doi: 10.3390/brainsci11111543. PMID: 34827542.
Ramic M, Andrade NS, Rybin MJ, Esanov R, Wahlestedt C, Benatar M, Zeier Z. Epigenetic Small Molecules Rescue Nucleocytoplasmic Transport and DNA Damage Phenotypes in C9ORF72 ALS/FTD. Brain Sci. 2021 Nov 20;11(11):1543. doi: 10.3390/brainsci11111543.
Puentes F, Lombardi V, Lu CH, Yildiz O, Fratta P, Isaacs A, Bobeva Y, Wuu J; ALS Biomarker Consortium; CReATe Consortium, Benatar M, Malaspina A. Humoral response to neurofilaments and dipeptide repeats in ALS progression. Ann Clin Transl Neurol. 2021 Sep;8(9):1831-1844. doi: 10.1002/acn3.51428. Epub 2021 Jul 27.
Lingor P, Koch JC, Statland JM, Hussain S, Hennecke C, Wuu J, Langbein T, Ahmed R, Günther R, Ilse B, Kassubek J, Kollewe K, Kuttler J, Leha A, Lengenfeld T, Meyer T, Neuwirth C, Tostmann R, Benatar M. Challenges and opportunities for Multi-National Investigator-Initiated clinical trials for ALS: European and United States collaborations. Amyotroph Lateral Scler Frontotemporal Degener. 2021 Aug;22(5-6):419-425. doi: 10.1080/21678421.2021.1879866. Epub 2021 Feb 3.
Si Y, Kazamel M, Benatar M, Wuu J, Kwon Y, Kwan T, Jiang N, Kentrup D, Faul C, Alesce L, King PH. FGF23, a novel muscle biomarker detected in the early stages of ALS. Sci Rep. 2021 Jun 8;11(1):12062. doi: 10.1038/s41598-021-91496-6.
Murdock BJ, Famie JP, Piecuch CE, Raue KD, Mendelson FE, Pieroni CH, Iniguez SD, Zhao L, Goutman SA, Feldman EL. NK cells associate with ALS in a sex- and age-dependent manner. JCI Insight. 2021 Jun 8;6(11):e147129. doi: 10.1172/jci.insight.147129.
DeJesus-Hernandez M, Aleff RA, Jackson JL, Finch NA, Baker MC, Gendron TF, Murray ME, McLaughlin IJ, Harting JR, Graff-Radford NR, Oskarsson B, Knopman DS, Josephs KA, Boeve BF, Petersen RC, Fryer JD, Petrucelli L, Dickson DW, Rademakers R, Ebbert MTW, Wieben ED, van Blitterswijk M.. Long-read targeted sequencing ucnovers clinicopathological associations for Cr0rf72-linked diseases. . 2021 May 7;144(4):1082-1088. doi: 10.1093/brain/awab006. PMID: 33889947.
Kessler C, Serna-Higuita LM, Rattay TW, Maetzler W, Wurster I, Hayer S, Wilke C, Hengel H, Reichbauer J, Armbruster M, Schöls L, Martus P, Schüle R. Neurofilament light chain is a cerebrospinal fluid biomarker in hereditary spastic paraplegia. Ann Clin Transl Neurol. 2021 May;8(5):1122-1131. doi: 10.1002/acn3.51358. Epub 2021 Apr 5.
Murdock BJ, Goutman SA, Boss J, Kim S, Feldman EL. Amyotrophic Lateral Sclerosis Survival Associates With Neutrophils in a Sex-specific Manner. Neurol Neuroimmunol Neuroinflamm. 2021 Feb 2;8(2):e953. doi: 10.1212/NXI.0000000000000953. Print 2021 Mar.
Granit V, Grignon AL, Wuu J, Katz J, Walk D, Hussain S, Hernandez J, Jackson C, Caress J, Yosick T, Smider N, Benatar M. Harnessing the power of the electronic health record for ALS research and quality improvement: CReATe CAPTURE-ALS and the ALS Toolkit. Muscle Nerve. 2022 Feb;65(2):154-161. doi: 10.1002/mus.27454. Epub 2021 Nov 16. PMID: 34730240; PMCID: PMC8752483.
Placek K, Benatar M, Wuu J, Rampersaud E, Hennessy L, Van Deerlin VM, Grossman M, Irwin DJ, Elman L, McCluskey L, Quinn C, Granit V, Statland JM, Burns TM, Ravits J, Swenson A, Katz J, Pioro EP, Jackson C, Caress J, So Y, Maiser S, Walk D, Lee EB, Trojanowski JQ, Cook P, Gee J, Sha J, Naj AC, Rademakers R; CReATe Consortium, Chen W, Wu G, Paul Taylor J, McMillan CT. Machine learning suggests polygenic risk for cognitive dysfunction in amyotrophic lateral sclerosis. EMBO Mol Med. 2021 Jan 11;13(1):e12595. doi: 10.15252/emmm.202012595. Epub 2020 Dec 3. PMID: 33270986; PMCID: PMC7799365.
Nel M, Mavundla T, Gultig K, Botha G, Mulder N, Benatar M, Wuu J, Cooley A, Myers J, Rampersaud E, Wu G, Heckmann JM. Repeats expansions in ATXN2, NOP56, NIPA1 and ATXN1 are not associated with ALS in Africans. IBRO Neurosci Rep. 2021 Feb 10;10:130-135. doi: 10.1016/j.ibneur.2021.02.002. eCollection 2021 Jun.
Shepheard SR, Karnaros V, Benyamin B, Schultz DW, Dubowsky M, Wuu J, Chataway T, Malaspina A, Benatar M, Rogers ML. Urinary neopterin: A novel biomarker of disease progression in amyotrophic lateral sclerosis. Eur J Neurol. 2021 Dec 29. doi: 10.1111/ene.15237. Epub ahead of print. PMID: 34967083.
Bereman MS, Kirkwood KI, Sabaretnam T, Furlong S, Rowe DB, Guillemin GJ, Mellinger AL, Muddiman DC. Metabolite Profiling Reveals Predictive Biomarkers and the Absence of β-Methyl Amino-l-alanine in Plasma from Individuals Diagnosed with Amyotrophic Lateral Sclerosis. J Proteome Res. 2020 Aug 7;19(8):3276-328. PMID: 32418425.
Habes M, Grothe MJ, Tunc B, McMillan C, Wolk DA, Davatzikos C. Disentangling Heterogeneity in Alzheimer's Disease and Related Dementias Using Data-Driven Methods. Biol Psychiatry. 2020 Jul 1;88(1):70-82. doi: 10.1016/j.biopsych.2020.01.016. Epub 2020 Jan 31.
Andrade N, Ramic M, Esanov R, et al. Dipeptide repeat proteins inhibit homology-directed DNA double strand break repair in C9ORF72 ALS/FTD. Mol Neurodegener. 2020 Feb 24;15(1):13. doi: 10.1186/s13024-020-00365-9. PMID: 32093728; PMCID: PMC7041170.
Figueroa-Romero C,1, Guo K,2, Murdock BJ, et al. Temporal evolution of the microbiome, immune system and epigenome with disease progression in ALS mice. Dis Model Mech. 2020 Feb 1; 13(2). PMCID: PMC6906635, PMID: 31597644.
Lombardi V, Carassiti D, Giovannoni G, Lu CH, Adiutori R, Malaspina A. The potential of neurofilaments analysis using dry-blood and plasma spots. Sci Rep. 2020 Jan 9;10(1):97. PMID: 31919375, PMCID: PMC6952412.
Benatar M, Zhang L, Wang L, Granit V, Statland J, Barohn R, Swenson A, Ravits J, Jackson C, Burns TM, Trivedi J, Pioro EP, Caress J, Katz J, McCauley JL, Rademakers R, Malaspina A, Ostrow LW, Wuu J; CReATe Consortium. Validation of serum neurofilaments as prognostic and potential pharmacodynamic biomarkers for ALS. Neurology. 2020 Jul 7;95(1):e59-e69. PMID: 32385188, PMCID: PMC7371380.
Farhan SMK, Howrigan DP, Abbott LE, Klim JR, Topp SD, Byrnes AE, Churchhouse C, Phatnani H, Smith BN, Rampersaud E, Wu G, Wuu J, Shatunov A, Iacoangeli A, Al Khleifat A, Mordes DA, Ghosh S; ALSGENS Consortium; FALS Consortium; Project MinE Consortium; CReATe Consortium, Eggan K, Rademakers R, McCauley JL, Schüle R, Züchner S, Benatar M, Taylor JP, Nalls M, Gotkine M, Shaw PJ, Morrison KE, Al-Chalabi A, Traynor B, Shaw CE, Goldstein DB, Harms MB, Daly MJ, Neale BM. Exome sequencing in amyotrophic lateral sclerosis implicates a novel gene, DNAJC7, encoding a heat-shock protein. Nat Neurosci. 2019 Dec; 22(12): 1966–1974. PMCID: PMC6919277, PMID: 31768050.
Edmonson MN, Patel AN, Hedges DJ, Wang Z, Rampersaud E, Kesserwan CA, Zhou X, Liu Y, Newman S, Rusch MC, McLeod CL, Wilkinson MR, Rice SV, Soussi T, Taylor JP, Benatar M, Becksfort JB, Nichols KE, Robison LL, Downing JR, Zhang J.. Pediatric Cancer Variant Pathogenicity Information Exchange (PeCanPIE): a cloud-based platform for curating and classifying germline variants. Genome Res. 2019 Sep;29(9):1555-1565. doi: 10.1101/gr.250357.119. Epub 2019 Aug 22. PMID: 31439692.
Aladesuyi Arogundade O, Stauffer JE, Saberi S, Diaz-Garcia S, Malik S, Basilim H, Rodriguez MJ, Ohkubo T, Ravits J. Antisense RNA foci are associated with nucleoli and TDP-43 mislocalization in C9orf72-ALS/FTD: a quantitative study. Acta Neuropathol. 2019 Mar;137(3):527-530. doi: 10.1007/s00401-018-01955-0. Epub 2019 Jan 21. PMID: 30666413; PMCID: PMC6397670.
Lingor P, Weber M, Camu W, et al. ROCK-ALS: Protocol for a Randomized, Placebo-Controlled, Double- Blind Phase IIa Trial of Safety, Tolerability and Efficacy of the Rho Kinase (ROCK) Inhibitor Fasudil in Amyotrophic Lateral Sclerosis. Front Neurol. 2019; 10: 293. PMCID: PMC6446974, PMID: 30972018.
Placek K, Baer GM, Elman L, McCluskey L, Hennessy L, Ferraro PM, Lee EB, Lee VMY, Trojanowski JQ, Van Deerlin VM, Grossman M, Irwin DJ, McMillan CT. UNC13A polymorphism contributes to frontotemporal disease in sporadic amyotrophic lateral sclerosis. Neurobiol Aging. 2019; 73:190-199. PMID:30368160, PMCID: PMC6251755.
Eidhof I, Baets J, Kamsteeg EJ, Deconinck T, van Ninhuijs L, Martin JJ, Schüle R, Züchner S, De Jonghe P, Schenck A, van de Warrenburg BP. GDAP2 mutations implicate susceptibility to cellular stress in a new form of cerebellar ataxia. Brain. 2018 Sep 1;141(9):2592-2604. doi: 10.1093/brain/awy198.
Pottier C, Rampersaud E, Baker M, Wu G, Wuu J, McCauley JL, Zuchner S, Schule R, Bermudez C, Hussain S, Cooley A, Wallace M, Zhang J, Taylor JP, Benatar M, Rademakers R. Identification of compound heterozygous variants in OPTN in an ALS-FTD patient from the CReATe consortium: a case report. Amyotroph Lateral Scler Frontotemporal Degener. 2018 Aug;19(5-6):469-471. doi: 10.1080/21678421.2018.1452947. Epub 2018 Mar 20. PMID: 29558868; PMCID: PMC6116528.
Chen J, Kostenko V, Pioro EP, Trapp BD. MR Imaging-based Estimation of Upper Motor Neuron Density in Patients with Amyotrophic Lateral Sclerosis: A Feasibility Study. Radiology. 2018 Jun;287(3):955-964. doi: 10.1148/radiol.2018162967. Epub 2018 Jan 23. PMID: 29361242; PMCID: PMC5978454.
Nicolas A, Kenna KP, Renton AE, Ticozzi N, Faghri F, Chia R, Dominov JA, Kenna BJ, Nalls MA, Keagle P, Rivera AM, van Rheenen W, Murphy NA, van Vugt JJFA, Geiger JT, Van der Spek RA, Pliner HA, Shankaracharya, Smith BN, Marangi G, Topp SD, Abramzon Y, Gkazi AS, Eicher JD, Kenna A; ITALSGEN Consortium, Mora G, Calvo A, Mazzini L, Riva N, Mandrioli J, Caponnetto C, Battistini S, Volanti P, La Bella V, Conforti FL, Borghero G, Messina S, Simone IL, Trojsi F, Salvi F, Logullo FO, D'Alfonso S, Corrado L, Capasso M, Ferrucci L; Genomic Translation for ALS Care (GTAC) Consortium, Moreno CAM, Kamalakaran S, Goldstein DB; ALS Sequencing Consortium, Gitler AD, Harris T, Myers RM; NYGC ALS Consortium, Phatnani H, Musunuri RL, Evani US, Abhyankar A, Zody MC; Answer ALS Foundation, Kaye J, Finkbeiner S, Wyman SK, LeNail A, Lima L, Fraenkel E, Svendsen CN, Thompson LM, Van Eyk JE, Berry JD, Miller TM, Kolb SJ, Cudkowicz M, Baxi E; Clinical Research in ALS and Related Disorders for Therapeutic Development (CReATe) Consortium, Benatar M, Taylor JP, Rampersaud E, Wu G, Wuu J; SLAGEN Consortium, Lauria G, Verde F, Fogh I, Tiloca C, Comi GP, Sorarù G, Cereda C; French ALS Consortium, Corcia P, Laaksovirta H, Myllykangas L, Jansson L, Valori M, Ealing J, Hamdalla H, Rollinson S, Pickering-Brown S, Orrell RW, et al. Genome-wide Analyses Identify KIF5A as a Novel ALS Gene. Neuron. 2018 Mar 21;97(6):1267-1288. doi: 10.1016/j.neuron.2018.02.027. PMID: 29566793; PMCID: PMC5867896.
Lassuthova P, Rebelo AP, Ravenscroft G, Lamont PJ, Davis MR, Manganelli F, Feely SM, Bacon C, Brožková DŠ, Haberlova J, Mazanec R, Tao F, Saghira C, Abreu L, Courel S, Powell E, Buglo E, Bis DM, Baxter MF, Ong RW, Marns L, Lee YC, Bai Y, Isom DG, Barro-Soria R, Chung KW, Scherer SS, Larsson HP, Laing NG, Choi BO, Seeman P, Shy ME, Santoro L, Zuchner S. Mutations in ATP1A1 Cause Dominant Charcot-Marie-Tooth Type 2. Am J Hum Genet. 2018 Mar 1;102(3):505-514. doi: 10.1016/j.ajhg.2018.01.023. PMID: 29499166; PMCID: PMC5985288.
Simone R, Balendra R, Moens TG, et al. G-quadruplex-binding small molecules ameliorate C9orf72 FTD/ALS pathology in vitro and in vivo. EMBO Mol Med. 2018 Jan;10(1):22-31. doi: 10.15252/emmm.201707850. PMID: 29113975; PMCID: PMC5760849.
Moens TG, Mizielinska S, Niccoli T, et al. Sense and antisense RNA are not toxic in Drosophila models of C9orf72-associated ALS/FTD. Acta Neuropathol. 2018;135(3):445-457. PMID:29380049.
Wilke C, Rattay TW, Hengel H, Zimmermann M, Brockmann K, Schöls L, Kuhle J, Schüle R, Synofzik M. Serum neurofilament light chain is increased in hereditary spastic paraplegias. Ann Clin Transl Neurol. 2018;5(7):876-882. PMID:30009206, PMCID: PMC6043776.
Karanevich AG, Weisbrod LJ, Jawdat O, Barohn RJ, Gajewski BJ, He J, Statland JM. Using automated electronic medical record data extraction to model ALS survival and progression. BMC Neurol. 2018;18(1):205. PMID:30547800, PMCID: PMC6295028.
Murdock BJ, Zhou T, Kashlan SR, Little RJ, Goutman SA, Feldman EL. Correlation of Peripheral Immunity With Rapid Amyotrophic Lateral Sclerosis Progression. JAMA neurology. 2017 Dec 1;74(12):1446-1454. doi: 10.1001/jamaneurol.2017.2255. PMID: 28973548; PMCID: PMC5822195.
Schöls L, Rattay TW, Martus P, Meisner C, Baets J, Fischer I, Jägle C, Fraidakis MJ, Martinuzzi A, Saute JA, Scarlato M, Antenora A, Stendel C, Höflinger P, Lourenco CM, Abreu L, Smets K, Paucar M, Deconinck T, Bis DM, Wiethoff S, Bauer P, Arnoldi A, Marques W, Jardim LB, Hauser S, Criscuolo C, Filla A, Züchner S, Bassi MT, Klopstock T, De Jonghe P, Björkhem I, Schüle R. Hereditary spastic paraplegia type 5: natural history, biomarkers and a randomized controlled trial. Brain. 2017 Dec 1;140(12):3112-3127. doi: 10.1093/brain/awx273. PMID: 29126212; PMCID: PMC5841036.
DeJesus-Hernandez M, Finch NA, Wang X, Gendron TF, Bieniek KF, Heckman MG, Vasilevich A, Murray ME, Rousseau L, Weesner R, Lucido A, Parsons M, Chew J, Josephs KA, Parisi JE, Knopman DS, Petersen RC, Boeve BF, Graff-Radford NR, de Boer J, Asmann YW, Petrucelli L, Boylan KB, Dickson DW, van Blitterswijk M, Rademakers R. In-depth clinico-pathological examination of RNA foci in a large cohort of C9ORF72 expansion carriers. Acta Neuropathol. 2017 Aug;134(2):255-269. doi: 10.1007/s00401-017-1725-7. Epub 2017 May 15. PMID: 28508101; PMCID: PMC5508036.
Jacquier A, Delorme C, Belotti E, Juntas-Morales R, Solé G, Dubourg O, Giroux M, Maurage CA, Castellani V, Rebelo A, Abrams A, Züchner S, Stojkovic T, Schaeffer L, Latour P. Cryptic amyloidogenic elements in mutant NEFH causing Charcot-Marie-Tooth 2 trigger aggresome formation and neuronal death. Acta Neuropathol Commun. 2017 Jul 14;5(1):55. doi: 10.1186/s40478-017-0457-1. PMID: 28709447; PMCID: PMC5513089.
Esanov R, Cabrera GT, Andrade NS, Gendron TF, Brown RH Jr, Benatar M, Wahlestedt C, Mueller C, Zeier Z. A C9ORF72 BAC mouse model recapitulates key epigenetic perturbations of ALS/FTD. Mol Neurodegener. 2017 Jun 12;12(1):46. doi: 10.1186/s13024-017-0185-9. PMID: 28606110; PMCID: PMC5468954.
Finch NA, Wang X, Baker MC, Heckman MG, Gendron TF, Bieniek KF, Wuu J, DeJesus-Hernandez M, Brown PH, Chew J, Jansen-West KR, Daughrity LM, Nicholson AM, Murray ME, Josephs KA, Parisi JE, Knopman DS, Petersen RC, Petrucelli L, Boeve BF, Graff-Radford NR, Asmann YW, Dickson DW, Benatar M, Bowser R, Boylan KB, Rademakers R, van Blitterswijk M. Abnormal expression of homeobox genes and transthyretin in C9ORF72 expansion carriers. Neurol Genet. 2017 Jun 7;3(4):e161. doi: 10.1212/NXG.0000000000000161. PMID: 28660252; PMCID: PMC5479438.
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Lakshmanan K, Liu BM. Impact of Point-of-Care Testing on Diagnosis, Treatment, and Surveillance of Vaccine-Preventable Viral Infections. Diagnostics (Basel). 2025 Jan 7;15(2):123. doi: 10.3390/diagnostics15020123.
Liu BM, Yao Q, Cruz-Cosme R, Yarbrough C, Draper K, Suslovic W, Muhammad I, Contes KM, Hillyard DR, Teng S, Tang Q. Genetic Conservation and Diversity of SARS-CoV-2 Envelope Gene Across Variants of Concern. J Med Virol. 2025 Jan;97(1):e70136. doi: 10.1002/jmv.70136.
Rollman TB, Berkebile ZW, Hicks DM, Hatfield JS, Chauhan P, Pravetoni M, Schleiss MR, Milligan GN, Morgan TK, Bierle CJ. CD4+ but not CD8+ T cells are required for protection against severe guinea pig cytomegalovirus infections. PLoS Pathog. 2024 Nov 4;20(11):e1012515. doi: 10.1371/journal.ppat.1012515. eCollection 2024 Nov.
Liu BM, Hayes AW. Mechanisms and Assessment of Genotoxicity of Metallic Engineered Nanomaterials in the Human Environment. Biomedicines. 2024 Oct 20;12(10):2401. doi: 10.3390/biomedicines12102401.
Liu BM. Epidemiological and clinical overview of the 2024 Oropouche virus disease outbreaks, an emerging/re-emerging neurotropic arboviral disease and global public health threat. J Med Virol. 2024 Sep;96(9):e29897. doi: 10.1002/jmv.29897.
Liu BM, Rakhmanina NY, Yang Z, Bukrinsky MI. Mpox (Monkeypox) Virus and Its Co-Infection with HIV, Sexually Transmitted Infections, or Bacterial Superinfections: Double Whammy or a New Prime Culprit?. Viruses. 2024 May 15;16(5):784. doi: 10.3390/v16050784.
Liu BM, Li NL, Wang R, Li X, Li ZA, Marion TN, Li K. Key roles for phosphorylation and the Coiled-coil domain in TRIM56-mediated positive regulation of TLR3-TRIF-dependent innate immunity. J Biol Chem. 2024 May;300(5):107249. doi: 10.1016/j.jbc.2024.107249. Epub 2024 Mar 29.
Seasely AR, Blanchard CT, Arora N, Battarbee AN, Casey BM, Dionne-Odom J, Leal SM Jr, Moates DB, Sinkey RG, Szychowski JM, Tita AT, Subramaniam A; CWRH's COVID-19 Working Group;. Maternal and Perinatal Outcomes Associated With the Omicron Variant of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Infection. Obstet Gyneco. 2022 Aug 1;140(2):262-265. doi: 10.1097/AOG.0000000000004849. Epub 2022 May 18. PMID: 35852277.
Seasely AR, Blanchard CT, Arora N, Battarbee AN, Casey BM, Dionne-Odom J, Leal SM Jr, Moates DB, Sinkey RG, Szychowski JM, Tita AT, Subramaniam A; CWRH COVID-19 Working Group. Maternal and Perinatal Outcomes Associated With the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Delta (B.1.617.2) Variant. Obstet Gynecol. 2021 Dec 1;138(6):842-844. doi: 10.1097/AOG.0000000000004607. PMID: 34592747.
McGowan EC, Wright BL, Ruffner MA, Pesek RD, Rothenberg ME, Spergel JM, Dellon ES, Aceves SS. Eosinophilic esophagitis: An allergy and immunology perspective on the updated guidelines. J Allergy Clin Immunol. 2025 May 6:S0091-6749(25)00510-X. doi: 10.1016/j.jaci.2025.04.026. Online ahead of print.
Trimarchi MP, Namjou-Khales B, Morgenstern NB, Rochman M, Chen X, Osswald G, Besse J, Shook M, Caldwell J, Lape M, Shota T, Weirauch MT, Ruffner M, Constantine G, Martin LJ, Kottyan LC, Rothenberg ME; Consortium of Eosinophilic Gastrointestinal Disease Researchers CEGIR. Multi-trait Analysis of GWAS Expands Eosinophilic Esophagitis Genetic Susceptibility and Polygenic Risk Scores. Res Sq [Preprint]. 2025 May 16:rs.3.rs-6630283. doi: 10.21203/rs.3.rs-6630283/v1.
Pyne AL, Uchida AM, Hazel MW, Pletneva MA, Allen-Brady K, Peterson KA. Differing Epithelial and Immunologic Activation Patterns Following Food Reintroduction Reveal Different Transcriptional Profiles in Active Eosinophilic Esophagitis. Gastroenterology. 2025 Mar;168(3):598-600.e3. doi: 10.1053/j.gastro.2024.10.024. Epub 2024 Oct 26.
Palmieri JM, Szafron V, Hearrell M, Anvari S, Chinn IK, Eubanks JD, Fernandez-Davila N, Gupta MR, Hajjar J, Lyter-Reed L, Noroski L, Reiland A, Seeborg F, Getts B, Kearney P, Butler H, Davis CM. Accuracy of bead-based epitope assay testing for peanut allergy diagnosis: Real-world pediatric population study. Ann Allergy Asthma Immunol. 2025 Feb 28:S1081-1206(25)00090-0. doi: 10.1016/j.anai.2025.02.010. Online ahead of print.
Pitt T, Hearrell M, Huang X, Staggers KA, Davis CM. The impact of the COVID-19 pandemic on multicultural families with food allergy. J Allergy Clin Immunol Glob. 2025 Feb 12;4(2):100438. doi: 10.1016/j.jacig.2025.100438. eCollection 2025 May.
Mehta P, Pan Z, Furuta GT, Kliewer K; Consortium of Eosinophilic Gastrointestinal Disease Researchers. Empiric elimination diets for eosinophilic esophagitis: Barriers, facilitators, and impact on quality of life. J Allergy Clin Immunol Pract. 2025 Feb;13(2):434-436. doi: 10.1016/j.jaip.2024.10.030. Epub 2024 Nov 1.
Kliewer KL, Abonia JP, Aceves SS, Atkins D, Bonis PA, Capocelli KE, Chehade M, Collins MH, Dellon ES, Fei L, Furuta GT, Gupta SK, Kagalwalla A, Leung J, Mir S, Mukkada VA, Pesek R, Rosenberg C, Shoda T, Spergel JM, Sun Q, Wechsler JB, Yang GY, Rothenberg ME. One-food versus 4-food elimination diet for pediatric eosinophilic esophagitis: A multisite randomized trial. J Allergy Clin Immunol. 2025 Feb;155(2):520-532. doi: 10.1016/j.jaci.2024.08.023. Epub 2024 Sep 2.
Schoepfer A, Asikainen S, Biedermann L, Kreienbuehl A, Godat A, Dommann C, Straumann A, Greuter T. Swallowed Topical Tacrolimus Induces Clinical and Histological Remission in a Subset of Patients with Severe Lymphocytic Esophagitis. Inflamm Intest Dis. 2025 Jan 21;10(1):41-49. doi: 10.1159/000542812. eCollection 2025 Jan-Dec.
Ketchem CJ, Jensen ET, Dai X, Anderson C, Kodroff E, Strobel MJ, Zicarelli A, Gray S, Cordell A, Hiremath G, Dellon ES. Segmental overlap is common in eosinophilic gastrointestinal diseases and impacts clinical presentation and treatment. Dis Esophagus. 2025 Jan 7;38(1):doaf011. doi: 10.1093/dote/doaf011.
Kim S, Ben-Baruch Morgenstern N, Osonoi K, Aceves SS, Arva NC, Chehade M, Collins MH, Dellon ES, Falk GW, Furuta GT, Gonsalves NP, Gupta SK, Hirano I, Hiremath G, Katzka DA, Khoury P, Leung J, Pesek R, Peterson KA, Pletneva MA, Spergel JM, Wechsler JB, Yang GY, Rothenberg ME, Shoda T. Nonepithelial Gene Expression Correlates With Symptom Severity in Adults With Eosinophilic Esophagitis. J Allergy Clin Immunol Pract. 2024 Dec;12(12):3346-3355.e1. doi: 10.1016/j.jaip.2024.05.015. Epub 2024 May 18. PMID: 38768900; PMCID: PMC11570700.
Eosinophilic esophagitis (EoE) is a disorder in which eosinophils (white blood cells of the immune system) build up in the esophagus, causing tissue damage. Symptoms can include difficulty swallowing, food getting stuck in the throat, vomiting, reflux, malnourishment, and poor appetite. Not much is known about the underlying causes of variation in EoE symptoms.
In this study, researchers explored the underlying causes of symptom severity in EoE. First, the team compared a validated patient-reported outcome metric with a set of transcripts expressed in the esophagus of 146 patients with EoE. Next, the team used single-cell RNA sequencing data to identify the cellular source of EoE genes and further analyzed patients with mild and severe symptoms.
Results reveal that EoE symptoms are correlated with nonepithelial esophageal gene expression. Authors note that these findings provide evidence that nonepithelial cells likely contribute to symptom severity.
Su BB, Blackmon W, Xu C, Holt C, Boateng N, Wang D, Szafron V, Anagnostou A, Anvari S, Davis CM. Diagnosis and management of shrimp allergy. Front Allergy. 2024 Oct 18;5:1456999. doi: 10.3389/falgy.2024.1456999. eCollection 2024.
Fulkerson PC, Lussier SJ, Bendixsen CG, Castina SM, Gebretsadik T, Marlin JS, Russell PB, Seibold MA, Everman JL, Moore CM, Snyder BM, Thompson K, Tregoning GS, Wellford S, Arbes SJ, Bacharier LB, Calatroni A, Camargo CA Jr, Dupont WD, Furuta GT, Gruchalla RS, Gupta RS, Hershey GK, Jackson DJ, Johnson CC, Kattan M, Liu AH, Murrison L, O'Connor GT, Phipatanakul W, Rivera-Spoljaric K, Rothenberg ME, Seroogy CM, Teach SJ, Zoratti EM, Togias A, Hartert TV, Heros Study Team OBOT. Human Epidemiology and Response to SARS-CoV-2 (HEROS): objectives, design, and enrollment results of a 12-city remote observational surveillance study of households with children, using direct-to-participant methods. Am J Epidemiol. 2024 Oct 7;193(10):1329-1338. doi: 10.1093/aje/kwae077.
Abonia JP, Rudman Spergel AK, Hirano I, Shoda T, Zhang X, Martin LJ, Mukkada VA, Putnam PE, Blacklidge M, Neilson D, Collins MH, Yang GY, Capocelli KE, Foote H, Eby M, Dong S, Aceves SS, Rothenberg ME; Consortium of Eosinophilic Gastrointestinal Disease Researchers. Losartan Treatment Reduces Esophageal Eosinophilic Inflammation in a Subset of Eosinophilic Esophagitis. J Allergy Clin Immunol Pract. 2024 Sep;12(9):2427-2438.e3. doi: 10.1016/j.jaip.2024.07.011. Epub 2024 Jul 25.
Wright BL, Abonia JP, Abud EM, Aceves SS, Ackerman SJ, Braskett M, Chang JW, Chehade M, Constantine GM, Davis CM, Dellon ES, Doyle AD, Durban R, Hill DA, Jensen ET, Kewalramani A, Khoury P, Klion AD, Kottyan L, Kuang FL, McGowan EC, Ruffner MA, Spencer LA, Spergel JM, Uchida AM, Wechsler JB, Pesek RD. Advances and ongoing challenges in eosinophilic gastrointestinal disorders presented at the CEGIR/TIGERs Symposium at the 2024 American Academy of Allergy, Asthma & Immunology meeting. J Allergy Clin Immunol. 2024 Aug 5:S0091-6749(24)00779-6. doi: 10.1016/j.jaci.2024.07.022. Online ahead of print.
Martin LJ, Zhang X, Chehade M, Davis CM, Dellon ES, Falk GW, Gupta SK, Hirano I, Hiremath GS, Katzka DA, Khoury P, Leung J, Menard-Katcher P, Gonsalves N, Pesek RD, Spergel JM, Wechsler JB, Kliewer K, Arva NC, Collins MH, Pletneva M, Yang GY, Furuta GT, Rothenberg ME, Aceves SS. Long-term durability between parent and child patient-reported outcomes in eosinophilic esophagitis. J Allergy Clin Immunol. 2024 Jul 25:S0091-6749(24)00740-1. doi: 10.1016/j.jaci.2024.07.011. Online ahead of print.
Eosinophilic esophagitis (EoE) is a disorder in which eosinophils (white blood cells of the immune system) build up in the esophagus, causing tissue damage. Symptoms include difficulty swallowing, food getting stuck in the throat, vomiting, reflux, malnourishment, and poor appetite. Because young children are unable to report their own symptoms, parents must report on the child’s behalf. However, not much is known about the long-term alignment of symptoms reported by parents and child patients.
In this study, researchers compared parent and child patient-reported outcomes in EoE over time. A total of 292 parent-child respondents completed 723 questionnaires about symptoms over a 5-year period, which researchers used to track long-term changes and similarities in reported outcomes.
Results show that there is strong long-term alignment between parent and child patient-reported outcomes. Authors note that these findings provide evidence that parent-report by proxy is an accurate means to monitor symptoms, which provides a framework for monitoring pediatric patients in clinical trials.
Godat A, Mueller R, Schenker D, Schoepfer AM, Straumann A, Greuter T; EoE Eosinophil Distribution Research Group. Eosinophil Distribution in Eosinophilic Esophagitis and its Impact on Disease Activity and Response to Treatment. Clin Gastroenterol Hepatol. 2024 Jul;22(7):1528-1530.e3. doi: 10.1016/j.cgh.2023.12.003. Epub 2023 Dec 16.
Furuta GT, Dellon ES, Straumann A, Gonsalves N, Rothenberg ME, Hirano I. Building and implementing a research infrastructure for eosinophilic gastrointestinal diseases. J Allergy Clin Immunol. 2024 Jun;153(6):1536-1539. doi: 10.1016/j.jaci.2024.04.014.
Burk CM, Shreffler WG. Triggers for eosinophilic esophagitis (EoE): The intersection of food allergy and EoE. J Allergy Clin Immunol. 2024 Jun;153(6):1500-1509. doi: 10.1016/j.jaci.2024.04.010.
Sato H, Dellon ES, Aceves SS, Arva NC, Chehade M, Collins MH, Davis CM, Falk GW, Furuta GT, Gonsalves NP, Gupta SK, Hirano I, Hiremath G, Katzka DA, Khoury P, Leung J, Menard-Katcher P, Pesek R, Peterson KA, Pletneva MA, Spergel JM, Wechsler JB, Yang GY, Rothenberg ME, Shoda T. Clinical and molecular correlates of the Index of Severity for Eosinophilic Esophagitis. J Allergy Clin Immunol. 2024 May 13:S0091-6749(24)00465-2. doi: 10.1016/j.jaci.2024.04.025. Online ahead of print.
Haugen EJ, Locke AK, Correa H, Baba JS, Mahadevan-Jansen A, Hiremath G. Characterization of lamina propria remodeling in pediatric eosinophilic esophagitis using second harmonic generation microscopy. Transl Med Commun. 2024;9(1):10. doi: 10.1186/s41231-024-00170-2. Epub 2024 Mar 22.
Chehade M, Wright BL, Walsh S, Bailey DD, Muir AB, Klion AD, Collins MH, Davis CM, Furuta GT, Gupta S, Khoury P, Peterson KA, Jensen ET. Challenging assumptions about the demographics of eosinophilic gastrointestinal diseases: A systematic review. J Allergy Clin Immunol Glob. 2024 Apr 16;3(3):100260. doi: 10.1016/j.jacig.2024.100260. eCollection 2024 Aug.
Greuter T, Katzka D. Endoscopic Features of Eosinophilic Gastrointestinal Diseases. Immunol Allergy Clin North Am. 2024 May;44(2):357-368. doi: 10.1016/j.iac.2024.01.007. Epub 2024 Feb 13.
Wilson BE, Sacta MA, Wright BL, Spergel J, Wolfset N. The Relationship Between Eosinophilic Esophagitis and Immunotherapy. Immunol Allergy Clin North Am. 2024 May;44(2):281-291. doi: 10.1016/j.iac.2024.01.001. Epub 2024 Feb 14.
Shoda T, Taylor RJ, Sakai N, Rothenberg ME. Common and disparate clinical presentations and mechanisms in different eosinophilic gastrointestinal diseases. J Allergy Clin Immunol. 2024 Jun;153(6):1472-1484. doi: 10.1016/j.jaci.2024.03.013. Epub 2024 Mar 28.
Dehbozorgi S, Ramsey N, Lee ASE, Coleman A, Varshney P, Davis CM. Addressing Health Equity in Food Allergy. J Allergy Clin Immunol Pract. 2024 Mar;12(3):570-577. doi: 10.1016/j.jaip.2024.01.026. Epub 2024 Jan 25.
Cohen-Mekelburg S, Jordan A, Kenney B, Burgess HJ, Chang JW, Hu HM, Tapper E, Langa KM, Levine DA, Waljee AK. Loneliness and Depressive Symptoms Are High Among Older Adults With Digestive Disease and Associated With Lower Perceived Health. Clin Gastroenterol Hepatol. 2024 Mar;22(3):621-629.e2. doi: 10.1016/j.cgh.2023.08.027. Epub 2023 Sep 9.
Macaluso M, Rothenberg ME, Ferkol T, Kuhnell P, Kaminski HJ, Kimberlin DW, Benatar M, Chehade M; Principal Investigators of the Rare Diseases Clinical Research Network – Cycle 4. Impact of the COVID-19 Pandemic on People Living With Rare Diseases and Their Families: Results of a National Survey. JMIR Public Health Surveill. 2024 Feb 14;10:e48430. doi: 10.2196/48430.
Greuter T, Straumann A, Fernandez-Marrero Y, Germic N, Hosseini A, Chanwangpong A, Yousefi S, Simon D, Collins MH, Bussmann C, Chehade M, Dellon ES, Furuta GT, Gonsalves N, Hirano I, Moawad FJ, Biedermann L, Safroneeva E, Schoepfer AM, Simon HU. A MULTICENTER LONG-TERM COHORT STUDY OF EOSINOPHILIC ESOPHAGITIS VARIANTS AND THEIR PROGRESSION TO EOE OVER TIME. Clin Transl Gastroenterol. 2024 Feb 6. doi: 10.14309/ctg.0000000000000664. Epub ahead of print. PMID: 38318864.
Eosinophilic esophagitis (EoE) is a disorder in which eosinophils (white blood cells of the immune system) build up in the esophagus (the tube that carries food from the mouth to the stomach), causing tissue damage. Recently, conditions with symptoms of esophageal dysfunction resembling EoE—but without high amounts of eosinophils in the esophagus—have been characterized as EoE variants. However, not much is known about the progression and severity of these variants.
In this study, researchers investigated the progression of EoE variants to EoE over time. The team assessed clinical, immuno-histological, and molecular features of 54 patients with EoE variants from six EoE centers. Findings were compared with features of EoE patients and healthy controls.
Results suggest a disease spectrum, based on transition from EoE variants to EoE. Authors note that genes associated with the progression to EoE may represent potential therapeutic targets early in the course of disease.
Chehade M, McGowan EC, Wright BL, Muir AB, Klion AD, Furuta GT, Jensen ET, Bailey DD. Barriers to Timely Diagnosis of Eosinophilic Gastrointestinal Diseases. J Allergy Clin Immunol Pract. 2024 Feb;12(2):302-308. doi: 10.1016/j.jaip.2023.12.020. Epub 2023 Dec 17.
Hirano I, Dellon ES, Falk GW, Gonsalves NP, Furuta GT, Bredenoord AJ; ASCENT WORKING GROUP. Ascending to New Heights for Novel Therapeutics for Eosinophilic Esophagitis. Gastroenterology. 2024 Jan;166(1):1-10. doi: 10.1053/j.gastro.2023.09.004. Epub 2023 Sep 9.
Heil A, Kuehlewindt T, Godat A, Simon HU, Simon D, Schreiner P, Saner C, Vavricka SR, Biedermann L, Safroneeva E, Rossel JB, Limacher A, Straumann A, Schoepfer AM, Greuter T. Histological Phenotyping in Eosinophilic Esophagitis: Localized Proximal Disease Is Infrequent but Associated with Less Severe Disease and Better Disease Outcome. Int Arch Allergy Immunol. 2024;185(1):63-72. doi: 10.1159/000533815. Epub 2023 Oct 20.
Ruffner MA, Shoda T, Lal M, Mrozek Z, Muir AB, Spergel JM, Dellon ES, Rothenberg ME. Persistent esophageal changes after histologic remission in eosinophilic esophagitis. J Allergy Clin Immunol. 2024 Apr;153(4):1063-1072. doi: 10.1016/j.jaci.2023.12.012. Epub 2023 Dec 27.
Peterson K, Collins MH, Aceves SS, Chehade M, Gonsalves N. Concepts and Controversies in Eosinophilic Esophagitis: What's Coming Down the Pipe?. Gastroenterology. 2024 Mar;166(3):382-395. doi: 10.1053/j.gastro.2023.10.035. Epub 2023 Dec 3.
Mehta P, Pan Z, Zhou W, Kwan BM, Furuta GT. Medication Adherence Rates in Adolescents With Eosinophilic Esophagitis Are Low and Are Associated With Health Habits. J Pediatr Gastroenterol Nutr. 2023 Oct 1;77(4):532-535. doi: 10.1097/MPG.0000000000003885. Epub 2023 Sep 20.
Chehade M, Wright BL, Atkins D, Aceves SS, Ackerman SJ, Assa'ad AH, Bauer M, Collins MH, Commins SP, Davis CM, Dellon ES, Doerfler B, Gleich GJ, Gupta SK, Hill DA, Jensen ET, Katzka D, Kliewer K, Kodroff E, Kottyan LC, Kyle S, Muir AB, Pesek RD, Peterson K, Shreffler WG, Spergel JM, Strobel MJ, Wechsler J, Zimmermann N, Furuta GT, Rothenberg ME. Breakthroughs in understanding and treating eosinophilic gastrointestinal diseases presented at the CEGIR/TIGERs Symposium at the 2022 American Academy of Allergy, Asthma & Immunology Meeting. J Allergy Clin Immunol. 2023 Sep 1:S0091-6749(23)01103-X. doi: 10.1016/j.jaci.2023.08.021. Online ahead of print.
Eosinophilic gastrointestinal disorders (EGIDs) are a group of chronic immune system disorders in which a type of white blood cell (eosinophils) build up in the gastrointestinal tract, causing inflammation or injury.
In February 2022, the American Academy of Allergy, Asthma, and Immunology hosted their annual meeting to discuss innovations in research. During the meeting, CEGIR and the International Gastrointestinal Eosinophil Researchers organized a day-long symposium focused on breakthrough discoveries in EGIDs.
The symposium featured a review of recent discoveries in the basic biology, pathogenesis, and clinical features of EGIDs. Topics included diagnostic and management approaches, as well as clinical trials of emerging therapies.
Kliewer KL, Murray-Petzold C, Collins MH, Abonia JP, Bolton SM, DiTommaso LA, Martin LJ, Zhang X, Mukkada VA, Putnam PE, Kellner ES, Devonshire AL, Schwartz JT, Kunnathur VA, Rosenberg CE, Lyles JL, Shoda T, Klion AD, Rothenberg ME. Benralizumab for eosinophilic gastritis: a single-site, randomised, double-blind, placebo-controlled, phase 2 trial. Lancet Gastroenterol Hepatol. 2023 Sep;8(9):803-815. doi: 10.1016/S2468-1253(23)00145-0. Epub 2023 Jun 16.
Mehta P, Pan Z, Zhou W, Burger C, Menard-Katcher C, Bailey DD, Furuta GT. Examining Disparities in Pediatric Eosinophilic Esophagitis. J Allergy Clin Immunol Pract. 2023 Sep;11(9):2855-2859. doi: 10.1016/j.jaip.2023.06.011. Epub 2023 Jun 14.
Gonsalves N, Doerfler B, Zalewski A, Yang GY, Martin LJ, Zhang X, Shoda T, Brusilovsky M, Aceves S, Thompson K, Rudman Spergel AK, Furuta G, Rothenberg ME, Hirano I. Prospective study of an amino acid-based elemental diet in an eosinophilic gastritis and gastroenteritis nutrition trial. J Allergy Clin Immunol. 2023 Sep;152(3):676-688. doi: 10.1016/j.jaci.2023.05.024. Epub 2023 Jul 18.
Uchida AM, Burk CM, Rothenberg ME, Furuta GT, Spergel JM. Recent Advances in the Treatment of Eosinophilic Esophagitis. J Allergy Clin Immunol Pract. 2023 Sep;11(9):2654-2663. doi: 10.1016/j.jaip.2023.06.035. Epub 2023 Jun 28.
Benitez AJ, McGar A, Kohser K, Gibbons T, Muir A, Mascarenhas M, Rossi C, Dogias F, Golden A, Kassam-Adams N, Marsac ML. The Cellie Coping Kit for children with Eosinophilic Esophagitis: Feasibility, acceptability, and preliminary outcomes. J Child Health Care. 2023 Sep;27(3):374-385. doi: 10.1177/13674935211064126. Epub 2022 Jan 3.
Rothenberg ME, Dellon ES, Collins MH, Hirano I, Chehade M, Bredenoord AJ, Lucendo AJ, Spergel JM, Sun X, Hamilton JD, Mortensen E, Laws E, Maloney J, Mannent LP, McCann E, Liu X, Glotfelty L, Shabbir A. Efficacy and safety of dupilumab up to 52 weeks in adults and adolescents with eosinophilic oesophagitis (LIBERTY EoE TREET study): a multicentre, double-blind, randomised, placebo-controlled, phase 3 trial. Lancet Gastroenterol Hepatol. 2023 Aug 31:S2468-1253(23)00204-2. doi: 10.1016/S2468-1253(23)00204-2. Online ahead of print.
Rubenstein JH, Fontaine S, MacDonald PW, Burns JA, Evans RR, Arasim ME, Chang JW, Firsht EM, Hawley ST, Saini SD, Wallner LP, Zhu J, Waljee AK. Predicting Incident Adenocarcinoma of the Esophagus or Gastric Cardia Using Machine Learning of Electronic Health Records. Gastroenterology. 2023 Dec;165(6):1420-1429.e10. doi: 10.1053/j.gastro.2023.08.011. Epub 2023 Aug 18.
Chehade M, Furuta G, Klion A, Abonia JP, Aceves S, Bose P, Collins MH, Davis C, Dellon ES, Eickel G, Falk G, Gupta S, Hiremath G, Howard A, Jensen ET, Kesh S, Khoury P, Kocher K, Kodroff E, Kyle S, Mak N, McCoy D, Mehta P, Menard-Katcher P, Mukkada V, Paliana A, Rothenberg M, Sable K, Schmitt C, Scott M, Spergel J, Strobel MJ, Wechsler JB, Yang GY, Zicarelli A, Muir AB, Wright BL, Bailey DD. Enhancing diversity, equity, inclusion, and accessibility in eosinophilic gastrointestinal disease research: the consortium for eosinophilic gastrointestinal disease researchers' journey. Ther Adv Rare Dis. 2023 Aug 14;4:26330040231180895. doi: 10.1177/26330040231180895. PMID: 37588777; PMCID: PMC10426297
Eosinophilic gastrointestinal diseases (EGIDs) are a group of chronic immune system disorders in which inflammation causes difficulties in daily life and the buildup of a type of white blood cell (eosinophils) in the gastrointestinal tract, which can lead to tissue damage and dysfunction.
To address systemic bias in patient care and research in EGIDs, the Consortium of Eosinophilic Gastrointestinal Disease Researchers (CEGIR) recently formed a diversity committee. The CEGIR diversity committee has defined its purpose through mission and vision statements. The committee has also developed structured educational and research initiatives to enhance diversity, equity, inclusivity, and accessibility (DEIA) in all CEGIR activities.
In this review article, researchers share the process of forming the diversity committee, highlighting milestones achieved and summarizing future directions. Authors hope that this report will serve as a guide and an inspiration for other researchers to enhance DEIA in their fields.
Chang JW, Kliewer K, Haller E, Lynett A, Doerfler B, Katzka DA, Peterson KA, Dellon ES, Gonsalves N; Consortium of Eosinophilic Gastrointestinal Disease Researchers. Development of a Practical Guide to Implement and Monitor Diet Therapy for Eosinophilic Esophagitis. Clin Gastroenterol Hepatol. 2023 Jul;21(7):1690-1698. doi: 10.1016/j.cgh.2023.03.006. Epub 2023 Mar 16.
Ben-Baruch Morgenstern N, Shoda T, Rochman Y, Caldwell JM, Collins MH, Mukkada V, Putnam PE, Bolton SM, Felton JM, Rochman M, Murray-Petzold C, Kliewer KL, Rothenberg ME. Local type 2 immunity in eosinophilic gastritis. J Allergy Clin Immunol. 2023 Jul;152(1):136-144. doi: 10.1016/j.jaci.2023.01.021. Epub 2023 Feb 7.
Leiman DA, Kamal AN, Otaki F, Bredenoord AJ, Dellon ES, Falk GW, Fernandez-Becker NQ, Gonsalves N, Hirano I, Katzka DA, Peterson K, Yadlapati R, Kathpalia P. Quality Indicators for the Diagnosis and Management of Eosinophilic Esophagitis. Am J Gastroenterol. 2023 Jun 1;118(6):1091-1095. doi: 10.14309/ajg.0000000000002138. Epub 2022 Dec 23.
Masuda MY, LeSuer WE, Horsley-Silva JL, Putikova A, Buras MR, Gibson JB, Pyon GC, Simmons TD, Doyle AD, Wright BL. Food-Specific IgG4 Is Elevated Throughout the Upper Gastrointestinal Tract in Eosinophilic Esophagitis. Dig Dis Sci. 2023 Jun;68(6):2406-2413. doi: 10.1007/s10620-023-07924-2. Epub 2023 Mar 27.
Gautam Y, Caldwell J, Kottyan L, Chehade M, Dellon ES, Rothenberg ME, Mersha TB; Consortium of Eosinophilic Gastrointestinal Disease Researchers (CEGIR) investigators. Genome-wide admixture and association analysis identifies African ancestry-specific risk loci of eosinophilic esophagitis in African Americans. J Allergy Clin Immunol. 2023 May;151(5):1337-1350. doi: 10.1016/j.jaci.2022.09.040. Epub 2022 Nov 15.
Kliewer KL, Gonsalves N, Dellon ES, Katzka DA, Abonia JP, Aceves SS, Arva NC, Besse JA, Bonis PA, Caldwell JM, Capocelli KE, Chehade M, Cianferoni A, Collins MH, Falk GW, Gupta SK, Hirano I, Krischer JP, Leung J, Martin LJ, Menard-Katcher P, Mukkada VA, Peterson KA, Shoda T, Rudman Spergel AK, Spergel JM, Yang GY, Zhang X, Furuta GT, Rothenberg ME. One-food versus six-food elimination diet therapy for the treatment of eosinophilic oesophagitis: a multicentre, randomised, open-label trial. Lancet Gastroenterol Hepatol. 2023 May;8(5):408-421. doi: 10.1016/S2468-1253(23)00012-2. Epub 2023 Feb 28.
Hirano I, Rothenberg ME, Zhang S, de Oliveira C, Charriez CM, Coyne KS, Bacci ED, Dellon ES. Dysphagia Days as an Assessment of Clinical Treatment Outcome in Eosinophilic Esophagitis. Am J Gastroenterol. 2023 Apr 1;118(4):744-747. doi: 10.14309/ajg.0000000000002094. Epub 2022 Dec 20.
Shoda T, Rochman M, Collins MH, Caldwell JM, Mack LE, Osswald GA, Mukkada VA, Putnam PE, Rothenberg ME. Molecular analysis of duodenal eosinophilia. J Allergy Clin Immunol. 2023 Apr;151(4):1027-1039. doi: 10.1016/j.jaci.2022.12.814. Epub 2022 Dec 30.
Salvador Nunes VS, Straumann A, Salvador Nunes L, Schoepfer AM, Greuter T. Eosinophilic Esophagitis beyond Eosinophils - an Emerging Phenomenon Overlapping with Eosinophilic Esophagitis: Collegium Internationale Allergologicum (CIA) Update 2023. Int Arch Allergy Immunol. 2023;184(5):411-420. doi: 10.1159/000529910. Epub 2023 Mar 27.
Hiremath G, Sun L, Collins MH, Bonis PA, Arva NC, Capocelli KE, Chehade M, Davis CM, Falk GW, Gonsalves N, Gupta SK, Hirano I, Leung J, Khoury P, Mukkada VA, Martin LJ, Spergel JM, Wechsler JB, Yang GY, Aceves SS, Furuta GT, Rothenberg ME, Koyama T, Dellon ES. Esophageal Epithelium and Lamina Propria Are Unevenly Involved in Eosinophilic Esophagitis. Clin Gastroenterol Hepatol. 2023 Mar 24:S1542-3565(23)00222-7. doi: 10.1016/j.cgh.2023.03.014. Online ahead of print.
Eosinophilic esophagitis (EoE) is a disorder in which eosinophils (white blood cells of the immune system) build up in the esophagus (the tube that carries food from the mouth to the stomach), causing tissue damage. The nature of the involvement of esophageal tissue has been unclear.
In this study, the investigators estimated the intrabiopsy site agreements of an established EoE histologic scoring system (EoEHSS) in the esophageal epithelial and lamina propria and examined if the disease activity status influenced the intrabiopsy site agreement. Comparisons were made between proximal:distal, proximal:middle, and middle:distal esophageal biopsy sites.
Results show that except for the extent of dilated intercellular spaces in inactive EoE, epithelial features and lamina propria were unevenly affected across esophageal biopsy sites, regardless of disease status. Authors note that these findings enhance our understanding of the effects of EoE on esophageal tissue pathology.
Applequist J, Burroughs C, Merkel PA, Rothenberg M, Trapnell B, Desnick R, Sahin M, Krischer J. Direct-to-Consumer Recruitment Methods via Traditional and Social Media to Aid in Research Accrual for Clinical Trials for Rare Diseases: Comparative Analysis Study. J Med Internet Res. 2023 Mar 14;25:e39262. doi: 10.2196/39262.
Furuta GT, Fillon SA, Williamson KM, Robertson CE, Stevens MJ, Aceves SS, Arva NC, Chehade M, Collins MH, Davis CM, Dellon ES, Falk GW, Gonsalves N, Gupta SK, Hirano I, Khoury P, Leung J, Martin LJ, Menard-Katcher P, Mukkada VA, Peterson K, Spergel JM, Wechsler JB, Yang GY, Rothenberg ME, Harris JK. Mucosal Microbiota Associated With Eosinophilic Esophagitis and Eosinophilic Gastritis. J Pediatr Gastroenterol Nutr. 2023 Mar 1;76(3):347-354. doi: 10.1097/MPG.0000000000003685. Epub 2022 Dec 16. PMID: 36525669.
Eosinophilic esophagitis (EoE) and eosinophilic gastritis (EoG) are disorders in which eosinophils (white blood cells) of the immune system build up as a reaction to foods or allergens, causing tissue damage. This immune response occurs in the esophagus in EoE and in the stomach in EoG. To better understand the association of gut microbiota (microorganisms in the digestive tract) with EoE and EoG, multicenter studies with large patient cohorts are needed.
In this study, researchers identified the mucosal microbiota associated with EoE and EoG in a geographically diverse cohort of patients. The team collected and analyzed clinical data, mucosal biopsies, and stool of pediatric and adult individuals with eosinophilic gastrointestinal disease (EGID) from 10 clinical sites within the Consortium of Eosinophilic Gastrointestinal Disease Researchers.
Not surprisingly, microbiome samples collected in the esophagus and stomach were not similar to those collected in the stool, thus emphasizing the importance of site-specific capture of data. Taxa associated with EGIDs varied highly among individuals. Authors note that further research is needed to determine if therapeutic interventions contribute to these differences.
Sindher SB, Barshow S, Tirumalasetty J, Arasi S, Atkins D, Bauer M, Bégin P, Collins MH, Deschildre A, Doyle AD, Fiocchi A, Furuta GT, Garcia-Lloret M, Mennini M, Rothenberg ME, Spergel JM, Wang J, Wood RA, Wright BL, Zuberbier T, Chin AR, Long A, Nadeau KC, Chinthrajah RS. The role of biologics in pediatric food allergy and eosinophilic gastrointestinal disorders. J Allergy Clin Immunol. 2023 Mar;151(3):595-606. doi: 10.1016/j.jaci.2023.01.007. PMID: 36872039; PMCID: PMC9993424.
Eosinophilic gastrointestinal disorders (EGIDs) are a group of chronic immune system disorders in which a type of white blood cell (eosinophils) build up in the gastrointestinal tract, causing inflammation or injury. EGIDs and food allergy (FA) share similar inflammatory mechanisms. Because of this, many of the same biologics (medications developed from biological sources) are being investigated to target these mechanisms in both EGIDs and FA.
In this review article, a team of researchers led by CEGIR scholars discuss the enormous potential of biologics for the treatment of EGIDs and FA in pediatric patients. Discussion includes past and current research into the use of biologics in FA and EGIDs, as well as their potential role in improving treatment options in the future. Authors also note the need for wider availability of biologics for clinical use.
Dellon ES, Spergel JM. Biologics in eosinophilic gastrointestinal diseases. Ann Allergy Asthma Immunol. 2023 Jan;130(1):21-27. doi: 10.1016/j.anai.2022.06.015. Epub 2022 Jun 20.
Underwood B, Troutman TD, Schwartz JT. Breaking down the complex pathophysiology of eosinophilic esophagitis. Ann Allergy Asthma Immunol. 2023 Jan;130(1):28-39. doi: 10.1016/j.anai.2022.10.026. Epub 2022 Nov 6.
Doyle AD, Masuda MY, Pyon GC, Luo H, Putikova A, LeSuer WE, Flashner S, Rank MA, Nakagawa H, Kita H, Wright BL. Detergent exposure induces epithelial barrier dysfunction and eosinophilic inflammation in the esophagus. Allergy. 2023 Jan;78(1):192-201. doi: 10.1111/all.15457. Epub 2022 Aug 8.
Chang JW, Kliewer K, Katzka DA, Peterson KA, Gonsalves N, Gupta SK, Furuta GT, Dellon ES. Provider Beliefs, Practices, and Perceived Barriers to Dietary Elimination Therapy in Eosinophilic Esophagitis. Am J Gastroenterol. 2022 Dec 1;117(12):2071-2074. doi: 10.14309/ajg.0000000000001988. Epub 2022 Sep 1. PMID: 36066475; PMCID: PMC9722505.
Eosinophilic esophagitis (EoE) is a disorder in which eosinophils (white blood cells of the immune system) build up in the esophagus (the tube that carries food from the mouth to the stomach), causing tissue damage. This immune response can occur as a reaction to certain foods. Although effective dietary treatments are often available, physicians tend to prefer medications. In this study, researchers assessed providers’ perceptions of EoE dietary therapy, including effectiveness, practice patterns, and barriers. The team collected this data through a web-based survey of providers. Results show that providers view diet as the least effective treatment for EoE. Barriers to treatment include the belief that patients are disinterested and unlikely to adhere. In addition, providers indicated that with less access to dietitians, nonacademic providers often manage diets without dietitian guidance. As patients are often highly accepting of diets and multiple treatment options for EoE, authors state that clinicians need evidence-based knowledge on EoE diets, access to dietitians, and awareness of patient preferences.
Arar AM, DeLay K, Leiman DA, Menard-Katcher P. Esophageal Manifestations of Dermatological Diseases, Diagnosis and Management. Curr Treat Options Gastroenterol. 2022 Dec;20(4):513-528. doi: 10.1007/s11938-022-00399-6. Epub 2022 Oct 18.
Robinson LB, Ruffner MA. Proton Pump Inhibitors in Allergy: Benefits and Risks. J Allergy Clin Immunol Pract. 2022 Dec;10(12):3117-3123. doi: 10.1016/j.jaip.2022.09.022. Epub 2022 Sep 23.
Rothenberg ME. Scientific journey to the first FDA-approved drug for eosinophilic esophagitis. J Allergy Clin Immunol. 2022 Dec;150(6):1325-1332. doi: 10.1016/j.jaci.2022.09.027. Epub 2022 Oct 6.
Masuda MY, Barshow SM, Garg S, Putikova A, LeSuer WE, Alexander JA, Katzka DA, Dellon ES, Kita H, Horsley-Silva JL, Doyle AD, Wright BL. Eosinophil Peroxidase Staining Enhances the Diagnostic Utility of the Cytosponge in Eosinophilic Esophagitis. Clin Transl Gastroenterol. 2022 Nov 1;13(11):e00534. doi: 10.14309/ctg.0000000000000534.
Namjou B, Lape M, Malolepsza E, DeVore SB, Weirauch MT, Dikilitas O, Jarvik GP, Kiryluk K, Kullo IJ, Liu C, Luo Y, Satterfield BA, Smoller JW, Walunas TL, Connolly J, Sleiman P, Mersha TB, Mentch FD, Hakonarson H, Prows CA, Biagini JM, Khurana Hershey GK, Martin LJ, Kottyan L; eMERGE Network. Multiancestral polygenic risk score for pediatric asthma. J Allergy Clin Immunol. 2022 Nov;150(5):1086-1096. doi: 10.1016/j.jaci.2022.03.035. Epub 2022 May 18.
Larey A, Aknin E, Daniel N, Osswald GA, Caldwell JM, Rochman M, Wasserman T, Collins MH, Arva NC, Yang GY, Rothenberg ME, Savir Y. Harnessing artificial intelligence to infer novel spatial biomarkers for the diagnosis of eosinophilic esophagitis. Front Med (Lausanne). 2022 Oct 21;9:950728. doi: 10.3389/fmed.2022.950728. eCollection 2022.
Ruffner MA, Cotton CC, Dellon ES. Posttreatment Gene Scores Support Histologic and Endoscopic Response Thresholds in Eosinophilic Esophagitis. Am J Gastroenterol. 2022 Sep 1;117(9):1519-1522. doi: 10.14309/ajg.0000000000001802. Epub 2022 Apr 26.
Wechsler JB, Bolton SM, Gray E, Kim KY, Kagalwalla AF. Defining the Patchy Landscape of Esophageal Eosinophilia in Children With Eosinophilic Esophagitis. Clin Gastroenterol Hepatol. 2022 Sep;20(9):1971-1976.e2. doi: 10.1016/j.cgh.2021.12.023. Epub 2021 Dec 23.
Wright BL. Should We Pretreat Before We Go Nuts? Antihistamines Modestly Reduce the Side Effects of Peanut Oral Immunotherapy. J Allergy Clin Immunol Pract. 2022 Sep;10(9):2395-2396. doi: 10.1016/j.jaip.2022.06.015.
Greuter T, Straumann A, Fernandez-Marrero Y, Germic N, Hosseini A, Yousefi S, Simon D, Collins MH, Bussmann C, Chehade M, Dellon ES, Furuta GT, Gonsalves N, Hirano I, Moawad FJ, Biedermann L, Safroneeva E, Schoepfer AM, Simon HU. Characterization of eosinophilic esophagitis variants by clinical, histological, and molecular analyses: A cross-sectional multi-center study. Allergy. 2022 Aug;77(8):2520-2533. doi: 10.1111/all.15233. Epub 2022 Feb 17. PMID: 35094416.
Eosinophilic esophagitis (EoE) is an allergic condition characterized by inflammation in the esophagus that causes a range of symptoms. Patients can have symptoms of esophageal dysfunction without meeting the classical diagnostic criteria. To characterize and classify the range of variants, an international team of researchers studied 69 patients with EoE variants. They identified and described three histological subtypes. Study authors concluded that EoE variants appear to be part of a disease spectrum, with classical EoE as the most common and apparent phenotype.
Wright BL, Schwartz JT, Ruffner MA, Furuta GT, Gonsalves N, Dellon ES, Aceves SS. Eosinophilic gastrointestinal diseases make a name for themselves: A new consensus statement with updated nomenclature. J Allergy Clin Immunol. 2022 Aug;150(2):291-293. doi: 10.1016/j.jaci.2022.05.012. Epub 2022 May 29. PMID: 35649464; PMCID: PMC9378528.
Eosinophilic gastrointestinal diseases (EGIDs) are a group of chronic immune system disorders in which a type of white blood cell (eosinophils) build up in the gastrointestinal tract, causing inflammation or injury. Consensus recommendations have been developed for diagnosis of eosinophilic esophagitis (EoE), the most common EGID. However, there are currently no consensus guidelines for diagnosis of non-EoE EGIDs. Standardization of EGID terminology is one of the first priorities for developing these guidelines. In this study, a large group of researchers and clinicians aimed to reach international consensus for EGID nomenclature. The team used multiple rounds of surveys to develop a new tiered framework for EGID terms. Authors note that this revision of terms could advance both clinical care and research in EGIDs. Next steps include selection of specific disease markers and thresholds, definition of symptoms, exclusion of alternative diagnoses, and duration of disease.
Seibold MA, Moore CM, Everman JL, Williams BJM, Nolin JD, Fairbanks-Mahnke A, Plender EG, Patel BB, Arbes SJ, Bacharier LB, Bendixsen CG, Calatroni A, Camargo CA Jr, Dupont WD, Furuta GT, Gebretsadik T, Gruchalla RS, Gupta RS, Khurana Hershey GK, Murrison LB, Jackson DJ, Johnson CC, Kattan M, Liu AH, Lussier SJ, O'Connor GT, Rivera-Spoljaric K, Phipatanakul W, Rothenberg ME, Seroogy CM, Teach SJ, Zoratti EM, Togias A, Fulkerson PC, Hartert TV; HEROS study team. Risk factors for SARS-CoV-2 infection and transmission in households with children with asthma and allergy: A prospective surveillance study. J Allergy Clin Immunol. 2022 Aug;150(2):302-311. doi: 10.1016/j.jaci.2022.05.014. Epub 2022 Jun 1. PMID: 35660376; PMCID: PMC9155183.
Children and people with asthma or other allergic diseases are typically known as high-risk groups for many respiratory viruses. However, it is currently unknown whether these groups are at increased risk for severe acute respiratory syndrome virus 2 (SARS-CoV-2) infection. In this study, researchers aimed to determine the incidence of SARS-CoV-2 infection in households with children, as well as whether self-reported asthma or other allergic diseases are associated with infection and household transmission. Participants included allergic disease patients from the Consortium of Eosinophilic Gastrointestinal Disease Researchers (CEGIR), which provided an accessible cohort for the study. For six months, the team collected biweekly nasal swabs and weekly surveys to calculate the probabilities of infection and transmission. Researchers then used regression analyses to determine associated risk factors. Results suggest that asthma does not increase the risk of SARS-CoV-2 infection. Food allergy was associated with lower infection risk, while body mass index was associated with increased infection risk. Authors note that understanding how these factors modify infection risk may offer new avenues for preventing infection.
Fulkerson PC, Lussier SJ, Bendixsen CG, Castina SM, Gebretsadik T, Marlin JS, Russell PB, Seibold MA, Everman JL, Moore CM, Snyder BM, Thompson K, Tregoning GS, Wellford S, Arbes SJ, Bacharier LB, Calatroni A, Camargo CA, Dupont WD, Furuta GT, Gruchalla RS, Gupta RS, Hershey GK, Jackson DJ, Johnson CC, Kattan M, Liu AH, Murrison L, Oâ Connor GT, Phipatanakul W, Rivera-Spoljaric K, Rothenberg ME, Seroogy CM, Teach SJ, Zoratti EM, Togias A, Hartert TV. Human Epidemiology and RespOnse to SARS-CoV-2 (HEROS): Objectives, Design and Enrollment Results of a 12-City Remote Observational Surveillance Study of Households with Children using Direct-to-Participant Methods. medRxiv. 2022 Jul 10:2022.07.09.22277457. doi: 10.1101/2022.07.09.22277457. Preprint.
Strauss AL, Falk GW. Refractory eosinophilic esophagitis: what to do when the patient has not responded to proton pump inhibitors, steroids and diet. Curr Opin Gastroenterol. 2022 Jul 1;38(4):395-401. doi: 10.1097/MOG.0000000000000842.
Dellon ES, Khoury P, Muir AB, Liacouras CA, Safroneeva E, Atkins D, Collins MH, Gonsalves N, Falk GW, Spergel JM, Hirano I, Chehade M, Schoepfer AM, Menard-Katcher C, Katzka DA, Bonis PA, Bredenoord AJ, Geng B, Jensen ET, Pesek RD, Feuerstadt P, Gupta SK, Lucendo AJ, Genta RM, Hiremath G, McGowan EC, Moawad FJ, Peterson KA, Rothenberg ME, Straumann A, Furuta GT, Aceves SS. A Clinical Severity Index for Eosinophilic Esophagitis: Development, Consensus, and Future Directions. J Allergy Clin Immunol. 2022 Jul;150(1):33-47. doi: 10.1016/j.jaci.2022.03.015. Epub 2022 May 20.
Dellon ES, Khoury P, Muir AB, Liacouras CA, Safroneeva E, Atkins D, Collins MH, Gonsalves N, Falk GW, Spergel JM, Hirano I, Chehade M, Schoepfer AM, Menard-Katcher C, Katzka DA, Bonis PA, Bredenoord AJ, Geng B, Jensen ET, Pesek RD, Feuerstadt P, Gupta SK, Lucendo AJ, Genta RM, Hiremath G, McGowan EC, Moawad FJ, Peterson KA, Rothenberg ME, Straumann A, Furuta GT, Aceves SS. A Clinical Severity Index for Eosinophilic Esophagitis: Development, Consensus, and Future Directions. Gastroenterology.. 2022 Jul;163(1):59-76. doi: 10.1053/j.gastro.2022.03.025. Epub 2022 May 20. PMID: 35606197; PMCID: PMC9233087.
For patients with eosinophilic esophagitis (EoE), an allergic inflammatory disease that damages the esophagus, therapeutic options and management are dictated by disease severity. However, the process for determining severity varies among practitioners. Reducing this variability could help improve clinicians’ ability to monitor EoE in an office setting. In this study, researchers aimed to create an international consensus severity scoring index for EoE. First, a group of adult and pediatric EoE researchers and clinicians—as well as non-EoE allergy immunology and gastroenterology experts—reviewed existing literature on EoE in the context of progression and severity. Next, a steering committee reached consensus on important features of severity. These features were then distilled to categorize patients with EoE as having inactive, mild, moderate, or severe disease. This new simplified scoring system, called the Index of Severity for Eosinophilic Esophagitis (I-SEE), can be completed at routine clinic visits. The system can help guide practitioners in EoE management by standardizing features of disease severity beyond eosinophil counts. To increase its utilization and functionality, authors note that I-SEE should be validated and refined using data from future clinical trials and routine clinical practice.
Daniel N, Larey A, Aknin E, Osswald GA, Caldwell JM, Rochman M, Collins MH, Yang GY, Arva NC, Capocelli KE, Rothenberg ME, Savir Y. A Deep Multi-Label Segmentation Network For Eosinophilic Esophagitis Whole Slide Biopsy Diagnostics. Annu Int Conf IEEE Eng Med Biol Soc. 2022 Jul;2022:3211-3217. doi: 10.1109/EMBC48229.2022.9871086.
Chang JW, Chen VL, Rubenstein JH, Dellon ES, Wallner LP, De Vries R. What patients with eosinophilic esophagitis may not share with their providers: a qualitative assessment of online health communities. Dis Esophagus. 2022 Jun 15;35(6):doab073. doi: 10.1093/dote/doab073. PMID: 34718475.
Zhang S, Shoda T, Aceves SS, Arva NC, Chehade M, Collins MH, Dellon ES, Falk GW, Gonsalves N, Gupta SK, Hirano I, Khoury P, Leung J, Spergel AKR, Spergel JM, Wechsler JB, Yang GY, Furuta GT, Rothenberg ME; Consortium of Eosinophilic Gastrointestinal Disease Researchers (CEGIR) Investigators Group. Mast cell-pain connection in eosinophilic esophagitis. Allergy. 2022 Jun;77(6):1895-1899. doi: 10.1111/all.15260. Epub 2022 Mar 3.
Bon L, Safroneeva E, Bussmann C, Biedermann L, Schreiner P, Vavricka SR, Schoepfer AM, McCright-Gill T, Simon HU, Straumann A, Chehade M, Greuter T. Close follow-up is associated with fewer stricture formation and results in earlier detection of histological relapse in the long-term management of eosinophilic esophagitis. United European Gastroenterol J. 2022 Apr;10(3):308-318. doi: 10.1002/ueg2.12216. Epub 2022 Apr 5. PMID: 35384368.
Safroneeva E, Pan Z, King E, Martin LJ, Collins MH, Yang GY, Capocelli KE, Arva NC, Abonia JP, Atkins D, Bonis PA, Dellon ES, Falk GW, Gonsalves N, Gupta SK, Hirano I, Leung J, Menard-Katcher PA, Mukkada VA, Schoepfer AM, Spergel JM, Wershil BK, Rothenberg ME, Aceves SS, Furuta GT; Consortium of Eosinophilic Gastrointestinal Disease Researchers. Long-Lasting Dissociation of Esophageal Eosinophilia and Symptoms After Dilation in Adults With Eosinophilic Esophagitis. Clin Gastroenterol Hepatol. 2022 Apr;20(4):766-775.e4. doi: 10.1016/j.cgh.2021.05.049. Epub 2021 May 29.
Dellon ES, Gonsalves N, Rothenberg ME, Hirano I, Chehade M, Peterson KA, Falk GW, Murray JA, Gehman LT, Chang AT, Singh B, Rasmussen HS, Genta RM. Determination of Biopsy Yield That Optimally Detects Eosinophilic Gastritis and/or Duodenitis in a Randomized Trial of Lirentelimab. Clin Gastroenterol Hepatol. 2022 Mar;20(3):535-545.e15. doi: 10.1016/j.cgh.2021.05.053. Epub 2021 Jun 2.
Rothenberg ME, Hottinger SKB, Gonsalves N, Furuta GT, Collins MH, Talley NJ, Peterson K, Menard-Katcher C, Smith M, Hirano I, Genta RM, Chehade M, Gupta SK, Spergel JM, Aceves SS, Dellon ES. Impressions and aspirations from the FDA GREAT VI Workshop on Eosinophilic Gastrointestinal Disorders Beyond Eosinophilic Esophagitis and Perspectives for Progress in the Field. J Allergy Clin Immunol. 2022 Mar;149(3):844-853. doi: 10.1016/j.jaci.2021.12.768. Epub 2021 Dec 22.
Dellon ES, Gonsalves N, Abonia JP, Alexander JA, Arva NC, Atkins D, Attwood SE, Auth MKH, Bailey DD, Biederman L, Blanchard C, Bonis PA, Bose P, Bredenoord AJ, Chang JW, Chehade M, Collins MH, Di Lorenzo C, Dias JA, Dohil R, Dupont C, Falk GW, Ferreira CT, Fox AT, Genta RM, Greuter T, Gupta SK, Hirano I, Hiremath GS, Horsley-Silva JL, Ishihara S, Ishimura N, Jensen ET, Gutiérrez-Junquera C, Katzka DA, Khoury P, Kinoshita Y, Kliewer KL, Koletzko S, Leung J, Liacouras CA, Lucendo AJ, Martin LJ, McGowan EC, Menard-Katcher C, Metz DC, Miller TL, Moawad FJ, Muir AB, Mukkada VA, Murch S, Nhu QM, Nomura I, Nurko S, Ohtsuka Y, Oliva S, Orel R, Papadopoulou A, Patel DA, Pesek RD, Peterson KA, Philpott H, Putnam PE, Richter JE, Rosen R, Ruffner MA, Safroneeva E, Schreiner P, Schoepfer A, Schroeder SR, Shah N, Souza RF, Spechler SJ, Spergel JM, Straumann A, Talley NJ, Thapar N, Vandenplas Y, Venkatesh RD, Vieira MC, von Arnim U, Walker MM, Wechsler JB, Wershil BK, Wright BL, Yamada Y, Yang GY, Zevit N, Rothenberg ME, Furuta GT, Aceves SS. International Consensus Recommendations for Eosinophilic Gastrointestinal Disease Nomenclature. Clin Gastroenterol Hepatol. 2022 Feb 16:S1542-3565(22)00143-4. doi: 10.1016/j.cgh.2022.02.017. Online ahead of print.
Hiremath G, Sun L, Correa H, Acra S, Collins MH, Bonis P, Arva NC, Capocelli KE, Falk GW, King E, Gonsalves N, Gupta SK, Hirano I, Mukkada VA, Martin LJ, Putnam PE, Spergel JM, Wechsler JB, Yang GY, Aceves SS, Furuta GT, Rothenberg ME, Koyama T, Dellon ES. Development and Validation of Web-Based Tool to Predict Lamina Propria Fibrosis in Eosinophilic Esophagitis. Am J Gastroenterol. 2022 Feb 1;117(2):272-279. doi: 10.14309/ajg.0000000000001587.
Dunn JLM, Rothenberg ME. 2021 year in review: Spotlight on eosinophils. J Allergy Clin Immunol. 2022 Feb;149(2):517-524. doi: 10.1016/j.jaci.2021.11.012. Epub 2021 Nov 25.
COREOS Collaborators:, Ma C, Schoepfer AM, Dellon ES, Bredenoord AJ, Chehade M, Collins MH, Feagan BG, Furuta GT, Gupta SK, Hirano I, Jairath V, Katzka DA, Pai RK, Rothenberg ME, Straumann A, Aceves SS, Alexander JA, Arva NC, Atkins D, Biedermann L, Blanchard C, Cianferoni A, Ciriza de Los Rios C, Clayton F, Davis CM, de Bortoli N, Dias JA, Falk GW, Genta RM, Ghaffari G, Gonsalves N, Greuter T, Hopp R, Hsu Blatman KS, Jensen ET, Johnston D, Kagalwalla AF, Larsson HM, Leung J, Louis H, Masterson JC, Menard-Katcher C, Menard-Katcher PA, Moawad FJ, Muir AB, Mukkada VA, Penagini R, Pesek RD, Peterson K, Putnam PE, Ravelli A, Savarino EV, Schlag C, Schreiner P, Simon D, Smyrk TC, Spergel JM, Taft TH, Terreehorst I, Vanuytsel T, Venter C, Vieira MC, Vieth M, Vlieg-Boerstra B, von Arnim U, Walker MM, Wechsler JB, Woodland P, Woosley JT, Yang GY, Zevit N, Safroneeva E. Development of a core outcome set for therapeutic studies in eosinophilic esophagitis (COREOS). J Allergy Clin Immunol. 2022 Feb;149(2):659-670. doi: 10.1016/j.jaci.2021.07.001. Epub 2021 Jul 6.
Min S, Shoda T, Wen T, Rothenberg ME. Diagnostic merits of the Eosinophilic Esophagitis Diagnostic Panel from a single esophageal biopsy. J Allergy Clin Immunol. 2022 Feb;149(2):782-787.e1. doi: 10.1016/j.jaci.2021.07.032. Epub 2021 Aug 8.
Hara T, Kasagi Y, Wang J, Sasaki M, Aaron B, Karami A, Shimonosono M, Shimonosono R, Maekawa H, Dolinsky L, Wilkins B, Klein J, Wei J, Nunes K, Lynch K, Spergel JM, Hamilton KE, Ruffner MA, Karakasheva TA, Whelan KA, Nakagawa H, Muir AB. CD73(+) Epithelial Progenitor Cells That Contribute to Homeostasis and Renewal Are Depleted in Eosinophilic Esophagitis. Cell Mol Gastroenterol Hepatol. 2022;13(5):1449-1467. doi: 10.1016/j.jcmgh.2022.01.018. Epub 2022 Jan 30.
Shoda T, Collins MH, Rochman M, Wen T, Caldwell JM, Mack LE, Osswald GA, Besse JA, Haberman Y, Aceves SS, Arva NC, Capocelli KE, Chehade M, Davis CM, Dellon ES, Falk GW, Gonsalves N, Gupta SK, Hirano I, Khoury P, Klion A, Menard-Katcher C, Leung J, Mukkada V, Putnam PE, Spergel JM, Wechsler JB, Yang GY, Furuta GT, Denson LA, Rothenberg ME; Consortium of Eosinophilic Gastrointestinal Diseases Researchers (CEGIR). Evaluating Eosinophilic Colitis as a Unique Disease using Colonic Molecular Profiles: A Multi-Site Study. Gastroenterology. 2022 Jan 24:S0016-5085(22)00038-5. doi: 10.1053/j.gastro.2022.01.022. Epub ahead of print. PMID: 35085569.
Hirano I, Collins MH, King E, Sun Q, Chehade M, Abonia JP, Bonis PA, Capocelli KE, Dellon ES, Falk GW, Gonsalves N, Gupta SK, Leung J, Katzka D, Menard-Katcher P, Khoury P, Klion A, Mukkada VA, Peterson K, Rudman-Spergel AK, Spergel JA, Yang GY, Rothenberg ME, Aceves SS, Furuta GT. Prospective Endoscopic Activity Assessment for Eosinophilic Gastritis in a Multisite Cohort. Am J Gastroenterol. 2022 Jan 20. doi: 10.14309/ajg.0000000000001625. Epub ahead of print. PMID: 35080202.
Trogen B, Jin H, Cianferoni A, Chehade M, Schultz F, Chavez A, Warren C, Nowak-Wegrzyn AH. A survey examining the impact of COVID-19 on food protein-induced enterocolitis syndrome. J Allergy Clin Immunol Pract. 2022 Jan;10(1):312-314.e3. doi: 10.1016/j.jaip.2021.10.053. Epub 2021 Nov 2.
Zevit N, Chehade M, Leung J, Marderfeld L, Dellon ES. Eosinophilic Esophagitis Patients Are Not at Increased Risk of Severe COVID-19: A Report From a Global Registry. J Allergy Clin Immunol Pract. 2022 Jan;10(1):143-149.e9. doi: 10.1016/j.jaip.2021.10.019. Epub 2021 Oct 22.
McGowan EC, Keller JP, Muir AB, Dellon ES, Peng R, Keet CA, Jensen ET. Distance to pediatric gastroenterology providers is associated with decreased diagnosis of eosinophilic esophagitis in rural populations. J Allergy Clin Immunol Pract. 2021 Dec;9(12):4489-4492.e2. doi: 10.1016/j.jaip.2021.08.034. Epub 2021 Sep 14. PMID: 34534720; PMCID: PMC8671202.
Qeadan F, Chehade M, Tingey B, Egbert J, Dellon ES, Peterson KA. Patients with eosinophilic gastrointestinal disorders have lower in-hospital mortality rates related to COVID-19. J Allergy Clin Immunol Pract. 2021 Dec;9(12):4473-4476.e4. doi: 10.1016/j.jaip.2021.09.022. Epub 2021 Sep 23. PMID: 34563741; PMCID: PMC8459462.
Hasan SH, Taylor S, Garg S, Buras MR, Doyle AD, Bauer CS, Wright BL, Schroeder S. Diagnosis of Pediatric Non-Esophageal Eosinophilic Gastrointestinal Disorders by Eosinophil Peroxidase Immunohistochemistry. Pediatr Dev Pathol. 2021 Nov-Dec;24(6):513-522. doi: 10.1177/10935266211024552. Epub 2021 Jun 28.
Muir A, Falk GW. Eosinophilic Esophagitis: A Review. JAMA. 2021 Oct 5;326(13):1310-1318. doi: 10.1001/jama.2021.14920.
Zimmermann N, Abonia JP, Dreskin SC, Akin C, Bolton S, Happel CS, Geller M, Larenas-Linnemann D, Nanda A, Peterson K, Wasan A, Wechsler J, Zhang S, Bernstein JA. Developing a standardized approach for assessing mast cells and eosinophils on tissue biopsies: A Work Group Report of the AAAAI Allergic Skin Diseases Committee. J Allergy Clin Immunol. 2021 Oct;148(4):964-983. doi: 10.1016/j.jaci.2021.06.030. Epub 2021 Aug 9. PMID: 34384610.
Melethil S, Abonia JP. A Gut-Wrenching Case of Hypereosinophilia. J Allergy Clin Immunol Pract. 2021 Sep;9(9):3524-3525. doi: 10.1016/j.jaip.2021.05.039. PMID: 34507713.
Chehade M, Aceves SS. Treatment of Eosinophilic Esophagitis: Diet or Medication?. J Allergy Clin Immunol Pract. 2021 Sep;9(9):3249-3256. doi: 10.1016/j.jaip.2021.07.029. PMID: 34507706.
Friedlander JA, Fleischer DM, Black JO, Levy M, Rothenberg ME, Smith C, Nguyen N, Pan Z, Furuta GT. Unsedated transnasal esophagoscopy with virtual reality distraction enables earlier monitoring of dietary therapy in eosinophilic esophagitis. J Allergy Clin Immunol Pract. 2021 Sep;9(9):3494-3496. doi: 10.1016/j.jaip.2021.06.030. Epub 2021 Jul 2. PMID: 34224927; PMCID: PMC8459391.
Ruffner MA, Zhang Z, Maurer K, Muir AB, Cianferoni A, Sullivan KE, Spergel JM. RNA sequencing identifies global transcriptional changes in peripheral CD4(+) cells during active oesophagitis and following epicutaneous immunotherapy in eosinophilic oesophagitis. Clin Transl Immunology. 2021 Jul 22;10(7):e1314. doi: 10.1002/cti2.1314. eCollection 2021.
Davis CM. Moving FORWARD Toward Racial Equity in Food Allergy. J Allergy Clin Immunol Pract. 2021 Jul;9(7):2874-2875. doi: 10.1016/j.jaip.2021.04.066.
Joshi S, Rubenstein JH, Dellon ES, Worthing N, Stefanadis Z, Chang JW. Variability in Practices of Compounding Budesonide for Eosinophilic Esophagitis. Am J Gastroenterol. 2021 Jun 1;116(6):1336-1338. doi: 10.14309/ajg.0000000000001170.
Sabet C, Klion AD, Bailey D, Jensen E, Chehade M, Abonia JP, Rothenberg ME, Furuta GT, Muir AB; CEGIR Investigator Group. Do rural health disparities affect prevalence data in pediatric eosinophilic esophagitis?. J Allergy Clin Immunol Pract. 2021 Jun;9(6):2549-2551. doi: 10.1016/j.jaip.2021.03.027.
Chang JW, Rubenstein JH, Mellinger JL, Kodroff E, Strobel MJ, Scott M, Mack D, Book W, Sable K, Kyle S, Paliana A, Dellon ES. Motivations, Barriers, and Outcomes of Patient-Reported Shared Decision Making in Eosinophilic Esophagitis. Dig Dis Sci. 2021 Jun;66(6):1808-1817. doi: 10.1007/s10620-020-06438-5. Epub 2020 Jul 3.
Chiang AWT, Duong LD, Shoda T, Nhu QM, Ruffner M, Hara T, Aaron B, Joplin E, Manresa MC, Abonia JP, Dellon ES, Hirano I, Gonsalves N, Gupta SK, Furuta GT, Rothenberg ME, Lewis NE, Muir AB, Aceves SS; CEGIR Investigator Group. Type 2 Immunity and Age Modify Gene Expression of Coronavirus-induced Disease 2019 Receptors in Eosinophilic Gastrointestinal Disorders. J Pediatr Gastroenterol Nutr. 2021 May 1;72(5):718-722. doi: 10.1097/MPG.0000000000003032.
Benitez AJ, Tanes C, Mattei L, Hofstaedter CE, Kim DK, Gross J, Ruffner MA, Albenberg L, Spergel J, Bittinger K, Muir AB. Effect of topical swallowed steroids on the bacterial and fungal esophageal microbiota in eosinophilic esophagitis. Allergy. 2021 May;76(5):1549-1552. doi: 10.1111/all.14602. Epub 2020 Oct 19.
Wechsler JB, Ackerman SJ, Chehade M, Amsden K, Riffle ME, Wang MY, Du J, Kleinjan ML, Alumkal P, Gray E, Kim KA, Wershil BK, Kagalwalla AF. Noninvasive biomarkers identify eosinophilic esophagitis: A prospective longitudinal study in children. Allergy. 2021 Apr 27. doi: 10.1111/all.14874. Online ahead of print.
Jacobsen EA, Jackson DJ, Heffler E, Mathur SK, Bredenoord AJ, Pavord ID, Akuthota P, Roufosse F, Rothenberg ME. Eosinophil Knockout Humans: Uncovering the Role of Eosinophils Through Eosinophil-Directed Biological Therapies. Annu Rev Immunol. 2021 Apr 26;39:719-757. doi: 10.1146/annurev-immunol-093019-125918. Epub 2021 Mar 1.
Wechsler JB, Schwartz S, Arva NC, Kim KA, Chen L, Makhija M, Amsden K, Keeley K, Mohammed S, Dellon ES, Kagalwalla AF. A Single-Food Milk Elimination Diet Is Effective for Treatment of Eosinophilic Esophagitis in Children. Clin Gastroenterol Hepatol. 2021 Apr 3:S1542-3565(21)00384-0. doi: 10.1016/j.cgh.2021.03.049. Online ahead of print.
Moore H, Wechsler J, Frost C, Whiteside E, Baldassano R, Markowitz J, Muir AB. Comorbid Diagnosis of Eosinophilic Esophagitis and Inflammatory Bowel Disease in the Pediatric Population. J Pediatr Gastroenterol Nutr. 2021 Mar 1;72(3):398-403. doi: 10.1097/MPG.0000000000003002.
Hamant L, Freeman C, Garg S, Wright BL, Schroeder S. Eosinophilic esophagitis may persist after discontinuation of oral immunotherapy. Ann Allergy Asthma Immunol. 2021 Mar;126(3):299-302. doi: 10.1016/j.anai.2020.12.007. Epub 2020 Dec 17.
Shoda T, Wen T, Caldwell JM, Ben-Baruch Morgenstern N, Osswald GA, Rochman M, Mack LE, Felton JM, Abonia JP, Arva NC, Atkins D, Bonis PA, Capocelli KE, Collins MH, Dellon ES, Falk GW, Gonsalves N, Gupta SK, Hirano I, Leung J, Menard-Katcher PA, Mukkada VA, Putnam PE, Rudman Spergel AK, Spergel JM, Wechsler JB, Yang GY, Aceves SS, Furuta GT, Rothenberg ME; Consortium of Eosinophilic Gastrointestinal Disease Researchers (CEGIR) Investigators Group. Loss of Endothelial TSPAN12 Promotes Fibrostenotic Eosinophilic Esophagitis via Endothelial Cell-Fibroblast Crosstalk. Gastroenterology. 2022 Feb;162(2):439-453. doi: 10.1053/j.gastro.2021.10.016. Epub 2021 Oct 21. PMID: 34687736; PMCID: PMC8792211.
Dellon ES, Shaheen O, Koutlas NT, Chang AO, Martin LJ, Rothenberg ME, Jensen ET. Early life factors are associated with risk for eosinophilic esophagitis diagnosed in adulthood. Dis Esophagus. 2021 Feb 10;34(2):doaa074. doi: 10.1093/dote/doaa074.
Schreiner P, Biedermann L, Greuter T, Wright BL, Straumann A. How to approach adult patients with asymptomatic esophageal eosinophilia. Dis Esophagus. 2021 Jan 11;34(1):doaa105. doi: 10.1093/dote/doaa105.
Doyle AD, Masuda MY, Kita H, Wright BL. Eosinophils in Eosinophilic Esophagitis: The Road to Fibrostenosis is Paved With Good Intentions. Front Immunol. 2020 Dec 1;11:603295. doi: 10.3389/fimmu.2020.603295. eCollection 2020.
Hiremath G, Krischer JP, Rothenberg ME, Dellon ES. Validation of self-reported diagnosis of eosinophilic gastrointestinal disorders patients enrolled in the CEGIR contact registry. Clin Res Hepatol Gastroenterol. 2020 Nov 5:101555. doi: 10.1016/j.clinre.2020.10.001. Online ahead of print.
Jensen ET, Aceves SS, Bonis PA, Bray K, Book W, Chehade M, Collins MH, Dellon ES, Falk GW, Gonsalves N, Gupta SK, Hirano I, Katzka DA, Kyle S, Mack D, Kodroff E, Leung J, Mukkada VA, Scott M, Paliana A, Sable K, Spergel JM, Strobel MJ, Krischer J, Rothenberg ME, Abonia P; CEGIR Investigator group. High Patient Disease Burden in a Cross-sectional, Multicenter Contact Registry Study of Eosinophilic Gastrointestinal Diseases. J Pediatr Gastroenterol Nutr. 2020 Oct;71(4):524-529. doi: 10.1097/MPG.0000000000002817.
Greuter T, Godat A, Ringel A, Almonte HS, Schupack D, Mendoza G, McCright-Gill T, Dellon ES, Hirano I, Alexander J, Chehade M, Safroneeva E, Bussmann C, Biedermann L, Schreiner P, Schoepfer AM, Straumann A, Katzka DA. Effectiveness and Safety of High- vs Low-Dose Swallowed Topical Steroids for Maintenance Treatment of Eosinophilic Esophagitis: A Multicenter Observational Study. Clin Gastroenterol Hepatol. 2020 Aug 13:S1542-3565(20)31136-8. doi: 10.1016/j.cgh.2020.08.027. Online ahead of print.
Pesek RD, Reed CC, Collins MH, Muir AB, Fulkerson PC, Menard-Katcher C, Falk GW, Kuhl J, Magier AZ, Ahmed FN, Demarshall M, Gupta A, Gross J, Ashorobi T, Carpenter CL, Krischer JP, Gonsalves N, Hirano I, Spergel JM, Gupta SK, Furuta GT, Rothenberg ME, Dellon ES; Consortium of Eosinophilic Gastrointestinal Disease Researchers (CEGIR). Association Between Endoscopic and Histologic Findings in a Multicenter Retrospective Cohort of Patients with Non-esophageal Eosinophilic Gastrointestinal Disorders. Dig Dis Sci. 2020 Jul;65(7):2024-2035. doi: 10.1007/s10620-019-05961-4. Epub 2019 Nov 26.
Chehade M, Brown S. Elimination diets for eosinophilic esophagitis: making the best choice. Expert Rev Clin Immunol. 2020 Jul;16(7):679-687. doi: 10.1080/1744666X.2020.1801419. Epub 2020 Aug 4.
Slack IF, Schwartz JT, Mukkada VA, Hottinger S, Abonia JP. Eosinophilic Esophagitis: Existing and Upcoming Therapies in an Age of Emerging Molecular and Personalized Medicine. Curr Allergy Asthma Rep. 2020 Jun 6;20(8):30. doi: 10.1007/s11882-020-00928-2.
Dunn JLM, Shoda T, Caldwell JM, Wen T, Aceves SS, Collins MH, Dellon ES, Falk GW, Leung J, Martin LJ, Menard-Katcher P, Rudman-Spergel AK, Spergel JM, Wechsler JB, Yang GY, Furuta GT, Rothenberg ME; Consortium of Eosinophilic Gastrointestinal Disease Researchers (CEGIR). Esophageal type 2 cytokine expression heterogeneity in eosinophilic esophagitis in a multisite cohort. J Allergy Clin Immunol. 2020 Jun;145(6):1629-1640.e4. doi: 10.1016/j.jaci.2020.01.051. Epub 2020 Mar 19.
Spergel JM, Brown-Whitehorn TA, Muir A, Liacouras CA. Medical algorithm: Diagnosis and treatment of eosinophilic esophagitis in children. Allergy. 2020 Jun;75(6):1522-1524. doi: 10.1111/all.14188. Epub 2020 Jan 31.
Whelan KA, Godwin BC, Wilkins B, Elci OU, Benitez A, DeMarshall M, Sharma M, Gross J, Klein-Szanto AJ, Liacouras CA, Dellon ES, Spergel JM, Falk GW, Muir AB, Nakagawa H. Persistent Basal Cell Hyperplasia Is Associated With Clinical and Endoscopic Findings in Patients With Histologically Inactive Eosinophilic Esophagitis. Clin Gastroenterol Hepatol. 2020 Jun;18(7):1475-1482.e1. doi: 10.1016/j.cgh.2019.08.055. Epub 2019 Sep 6.
Hirano I, Chan ES, Rank MA, Sharaf RN, Stollman NH, Stukus DR, Wang K, Greenhawt M, Falck-Ytter YT; AGA Institute Clinical Guidelines Committee; Joint Task Force on Allergy-Immunology Practice Parameters. AGA institute and the joint task force on allergy-immunology practice parameters clinical guidelines for the management of eosinophilic esophagitis. Ann Allergy Asthma Immunol. 2020 May;124(5):416-423. doi: 10.1016/j.anai.2020.03.020.
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Nhu QM, Hsieh L, Dohil L, Dohil R, Newbury RO, Kurten R, Moawad FJ, Aceves SS. Antifibrotic Effects of the Thiazolidinediones in Eosinophilic Esophagitis Pathologic Remodeling: A Preclinical Evaluation. Clin Transl Gastroenterol. 2020 Apr;11(4):e00164. doi: 10.14309/ctg.0000000000000164.
Cafone J, Ruffner MA, Spergel JM. The role of eosinophils in immunotherapy. Curr Opin Allergy Clin Immunol. 2020 Apr;20(2):329. doi: 10.1097/ACI.0000000000000617.
Applequist J, Burroughs C, Ramirez A Jr, Merkel PA, Rothenberg ME, Trapnell B, Desnick RJ, Sahin M, Krischer JP. A novel approach to conducting clinical trials in the community setting: utilizing patient-driven platforms and social media to drive web-based patient recruitment. BMC Med Res Methodol. 2020 Mar 13;20(1):58. doi: 10.1186/s12874-020-00926-y.
Hirano I, Furuta GT. Approaches and Challenges to Management of Pediatric and Adult Patients With Eosinophilic Esophagitis. Gastroenterology. 2020 Mar;158(4):840-851. doi: 10.1053/j.gastro.2019.09.052. Epub 2019 Dec 10.
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Whelan KA, Muir AB, Nakagawa H. Esophageal 3D Culture Systems as Modeling Tools in Esophageal Epithelial Pathobiology and Personalized Medicine. Cell Mol Gastroenterol Hepatol. 2018 Jan 31;5(4):461-478. doi: 10.1016/j.jcmgh.2018.01.011. eCollection 2018.
Kasagi Y, Chandramouleeswaran PM, Whelan KA, Tanaka K, Giroux V, Sharma M, Wang J, Benitez AJ, DeMarshall M, Tobias JW, Hamilton KE, Falk GW, Spergel JM, Klein-Szanto AJ, Rustgi AK, Muir AB, Nakagawa H. The Esophageal Organoid System Reveals Functional Interplay Between Notch and Cytokines in Reactive Epithelial Changes. Cell Mol Gastroenterol Hepatol. 2018 Jan 3;5(3):333-352. doi: 10.1016/j.jcmgh.2017.12.013. eCollection 2018 Mar.
Collins MH, Capocelli K, Yang GY. Eosinophilic Gastrointestinal Disorders Pathology. Front Med (Lausanne). 2018 Jan 15;4:261. doi: 10.3389/fmed.2017.00261. eCollection 2017.
Dellon ES, Hirano I. Epidemiology and Natural History of Eosinophilic Esophagitis. Gastroenterology. 2018 Jan;154(2):319-332.e3. doi: 10.1053/j.gastro.2017.06.067. Epub 2017 Aug 1.
Safroneeva E, Straumann A, Schoepfer AM. Latest Insights on the Relationship Between Symptoms and Biologic Findings in Adults with Eosinophilic Esophagitis. Gastrointest Endosc Clin N Am. 2018 Jan;28(1):35-45. doi: 10.1016/j.giec.2017.08.001.
O'Shea KM, Aceves SS, Dellon ES, Gupta SK, Spergel JM, Furuta GT, Rothenberg ME. Pathophysiology of Eosinophilic Esophagitis. Gastroenterology. 2018 Jan;154(2):333-345. doi: 10.1053/j.gastro.2017.06.065. Epub 2017 Jul 27.
Cheng K, Gupta SK, Kantor S, Kuhl JT, Aceves SS, Bonis PA, Capocelli KE, Carpenter C, Chehade M, Collins MH, Dellon ES, Falk GW, Gopal-Srivastava R, Gonsalves N, Hirano I, King EC, Leung J, Krischer JP, Mukkada VA, Schoepfer A, Spergel JM, Straumann A, Yang GY, Furuta GT, Rothenberg ME. Creating a multi-center rare disease consortium - the Consortium of Eosinophilic Gastrointestinal Disease Researchers (CEGIR). Transl Sci Rare Dis. 2017 Dec 18;2(3-4):141-155. doi: 10.3233/TRD-170016.
Eluri S, Dellon ES. Toward More Efficient Dietary Elimination Therapy for Eosinophilic Esophagitis: The Fantastic 4?. Clin Gastroenterol Hepatol. 2017 Nov;15(11):1668-1670. doi: 10.1016/j.cgh.2017.07.022. Epub 2017 Jul 26.
Caldwell JM, Paul M, Rothenberg ME. Novel immunologic mechanisms in eosinophilic esophagitis. Curr Opin Immunol. 2017 Oct;48:114-121. doi: 10.1016/j.coi.2017.08.006. Epub 2017 Sep 29.
Case C, Furuta GT, Atkins D, Pan Z, Robinson J. Diet and Stress in Pediatric Eosinophilic Esophagitis. J Pediatr Gastroenterol Nutr. 2017 Sep;65(3):281-284. doi: 10.1097/MPG.0000000000001481.
Menard-Katcher C, Benitez AJ, Pan Z, Ahmed FN, Wilkins BJ, Capocelli KE, Liacouras CA, Verma R, Spergel JM, Furuta GT, Muir AB. Influence of Age and Eosinophilic Esophagitis on Esophageal Distensibility in a Pediatric Cohort. Am J Gastroenterol. 2017 Sep;112(9):1466-1473. doi: 10.1038/ajg.2017.131. Epub 2017 May 16.
Pesek RD, Rettiganti M, O'Brien E, Beckwith S, Daniel C, Luo C, Scurlock AM, Chandler P, Levy RA, Perry TT, Kennedy JL, Chervinskiy S, Vonlanthen M, Casteel H, Fiedorek SC, Gibbons T, Jones SM. Effects of allergen sensitization on response to therapy in children with eosinophilic esophagitis. Ann Allergy Asthma Immunol. 2017 Aug;119(2):177-183. doi: 10.1016/j.anai.2017.06.006. Epub 2017 Jul 1.
Abonia JP, Spergel JM, Cianferoni A. Eosinophilic Esophagitis: A Primary Disease of the Esophageal Mucosa. J Allergy Clin Immunol Pract. 2017 Jul-Aug;5(4):951-955. doi: 10.1016/j.jaip.2017.02.004. Epub 2017 Mar 28.
Dellon ES. Management of refractory eosinophilic oesophagitis. Nat Rev Gastroenterol Hepatol. 2017 Aug;14(8):479-490. doi: 10.1038/nrgastro.2017.56. Epub 2017 May 24.
Hirano I, Spechler S, Furuta G, Dellon ES. White Paper AGA: Drug Development for Eosinophilic Esophagitis. Clin Gastroenterol Hepatol. 2017 Aug;15(8):1173-1183. doi: 10.1016/j.cgh.2017.03.016. Epub 2017 Mar 22.
Wen T, Rothenberg ME. Clinical Applications of the Eosinophilic Esophagitis Diagnostic Panel. Front Med (Lausanne). 2017 Jul 14;4:108. doi: 10.3389/fmed.2017.00108. eCollection 2017.
Whelan KA, Merves JF, Giroux V, Tanaka K, Guo A, Chandramouleeswaran PM, Benitez AJ, Dods K, Que J, Masterson JC, Fernando SD, Godwin BC, Klein-Szanto AJ, Chikwava K, Ruchelli ED, Hamilton KE, Muir AB, Wang ML, Furuta GT, Falk GW, Spergel JM, Nakagawa H. Autophagy mediates epithelial cytoprotection in eosinophilic oesophagitis. Gut. 2017 Jul;66(7):1197-1207. doi: 10.1136/gutjnl-2015-310341. Epub 2016 Feb 16.
Eluri S, Book WM, Kodroff E, Strobel MJ, Gebhart JH, Jones PD, Menard-Katcher P, Ferris ME, Dellon ES. Lack of Knowledge and Low Readiness for Health Care Transition in Eosinophilic Esophagitis and Eosinophilic Gastroenteritis. J Pediatr Gastroenterol Nutr. 2017 Jul;65(1):53-57. doi: 10.1097/MPG.0000000000001415.
Molina-Infante J, Hirano I, Spechler SJ; PPI-REE Task Force of the European Society of Eosinophilic Oesophagitis (EUREOS). Clarifying misunderstandings and misinterpretations about proton pump inhibitor-responsive oesophageal eosinophilia. Gut. 2017 Jun;66(6):1173-1174. doi: 10.1136/gutjnl-2016-312851. Epub 2016 Sep 13.
Atkins D, Furuta GT, Liacouras CA, Spergel JM. Eosinophilic esophagitis phenotypes: Ready for prime time?. Pediatr Allergy Immunol. 2017 Jun;28(4):312-319. doi: 10.1111/pai.12715. Epub 2017 May 4.
Menard-Katcher C, Furuta GT, Kramer RE. Dilation of Pediatric Eosinophilic Esophagitis: Adverse Events and Short-term Outcomes. J Pediatr Gastroenterol Nutr. 2017 May;64(5):701-706. doi: 10.1097/MPG.0000000000001336.
Muir AB, Wang ML, Metz D, Falk G, Markowitz J, Spergel JM, Liacouras CA. Proton pump inhibitor-responsive oesophageal eosinophilia: too early to change clinical practice. Gut. 2017 May;66(5):979-980. doi: 10.1136/gutjnl-2016-312601. Epub 2016 Jul 26.
Mehta P, Sundaram SS, Furuta GT, Pan Z, Atkins D, Markowitz S. Propofol Use in Pediatric Patients With Food Allergy and Eosinophilic Esophagitis. J Pediatr Gastroenterol Nutr. 2017 Apr;64(4):546-549. doi: 10.1097/MPG.0000000000001291.
Furuta GT, Aceves SS. The National Biome Initiative: An allergy perspective. J Allergy Clin Immunol. 2017 Apr;139(4):1131-1134. doi: 10.1016/j.jaci.2017.02.008. Epub 2017 Feb 28.
Hill DA, Dudley JW, Spergel JM. The Prevalence of Eosinophilic Esophagitis in Pediatric Patients with IgE-Mediated Food Allergy. J Allergy Clin Immunol Pract. 2017 Mar-Apr;5(2):369-375. doi: 10.1016/j.jaip.2016.11.020. Epub 2016 Dec 30.
Collins MH, Martin LJ, Alexander ES, Boyd JT, Sheridan R, He H, Pentiuk S, Putnam PE, Abonia JP, Mukkada VA, Franciosi JP, Rothenberg ME. Newly developed and validated eosinophilic esophagitis histology scoring system and evidence that it outperforms peak eosinophil count for disease diagnosis and monitoring. Dis Esophagus. 2017 Feb 1;30(3):1-8. doi: 10.1111/dote.12470.
Nguyen N, Furuta GT, Menard-Katcher C. Sticky Steroids: In Search of an Approved Treatment for Eosinophilic Esophagitis. J Pediatr Gastroenterol Nutr. 2017 Feb;64(2):172-173. doi: 10.1097/MPG.0000000000001326.
Atkins D. Aeroallergens in Eosinophilic Esophagitis: Significant Triggers or Noise in the System?. J Pediatr Gastroenterol Nutr. 2017 Jan;64(1):1-2. doi: 10.1097/MPG.0000000000001268.
Dellon ES, Collins MH, Bonis PA, Leung J, Capocelli KE, Dohil R, Falk GW, Furuta GT, Menard-Katcher C, Gupta SK, Hirano I, Hiremath GS, Kagalwalla AF, Wershil BK, Liacouras CA, Muir AB, Mukkada VA, Putnam PE, Schoepfer AM, Straumann A, Wo JM, Yang GY, Rothenberg ME, Gonsalves N. Substantial Variability in Biopsy Practice Patterns Among Gastroenterologists for Suspected Eosinophilic Gastrointestinal Disorders. Clin Gastroenterol Hepatol. 2016 Dec;14(12):1842-1844. doi: 10.1016/j.cgh.2016.04.025. Epub 2016 Apr 22.
Venter C, Fleischer DM. Diets for diagnosis and management of food allergy: The role of the dietitian in eosinophilic esophagitis in adults and children. Ann Allergy Asthma Immunol. 2016 Nov;117(5):468-471. doi: 10.1016/j.anai.2016.08.003. Epub 2016 Aug 31.
Rosenberg HF, Masterson JC, Furuta GT. Eosinophils, probiotics, and the microbiome. J Leukoc Biol. 2016 Nov;100(5):881-888. doi: 10.1189/jlb.3RI0416-202R. Epub 2016 Aug 22.
Ruffner MA, Spergel JM. Non-IgE-mediated food allergy syndromes. Ann Allergy Asthma Immunol. 2016 Nov;117(5):452-454. doi: 10.1016/j.anai.2016.04.014. Epub 2016 Oct 24.
Wen T, Rothenberg ME. The Regulatory Function of Eosinophils. Microbiol Spectr. 2016 Oct;4(5):10.1128/microbiolspec.MCHD-0020-2015. doi: 10.1128/microbiolspec.MCHD-0020-2015.
Morris DW, Stucke EM, Martin LJ, Abonia JP, Mukkada VA, Putnam PE, Rothenberg ME, Fulkerson PC. Eosinophil progenitor levels are increased in patients with active pediatric eosinophilic esophagitis. J Allergy Clin Immunol. 2016 Sep;138(3):915-918.e5. doi: 10.1016/j.jaci.2016.03.027. Epub 2016 May 16.
Muir AB, Benitez AJ, Dods K, Spergel JM, Fillon SA. Microbiome and its impact on gastrointestinal atopy. Allergy. 2016 Sep;71(9):1256-63. doi: 10.1111/all.12943. Epub 2016 Jun 23.
Rawson R, Yang T, Newbury RO, Aquino M, Doshi A, Bell B, Broide DH, Dohil R, Kurten R, Aceves SS. TGF-β1-induced PAI-1 contributes to a profibrotic network in patients with eosinophilic esophagitis. J Allergy Clin Immunol. 2016 Sep;138(3):791-800.e4. doi: 10.1016/j.jaci.2016.02.028. Epub 2016 Apr 8.
Nguyen N, Furuta GT, Masterson JC. Deeper Than the Epithelium: Role of Matrix and Fibroblasts in Pediatric and Adult Eosinophilic Esophagitis. J Pediatr Gastroenterol Nutr. 2016 Aug;63(2):168-9. doi: 10.1097/MPG.0000000000001183.
Muir AB, Dods K, Henry SJ, Benitez AJ, Lee D, Whelan KA, DeMarshall M, Hammer DA, Falk G, Wells RG, Spergel J, Nakagawa H, Wang ML. Eosinophilic Esophagitis-Associated Chemical and Mechanical Microenvironment Shapes Esophageal Fibroblast Behavior. J Pediatr Gastroenterol Nutr. 2016 Aug;63(2):200-9. doi: 10.1097/MPG.0000000000001100.
Imam T, Gupta SK. Topical glucocorticoid vs. diet therapy in eosinophilic esophagitis: the need for better treatment options. Expert Rev Clin Immunol. 2016 Aug;12(8):797-9. doi: 10.1080/1744666X.2016.1191947. Epub 2016 Jun 13.
Kia L, Hirano I. Advances in the endoscopic evaluation of eosinophilic esophagitis. Curr Opin Gastroenterol. 2016 Jul;32(4):325-31. doi: 10.1097/MOG.0000000000000278.
Hirano I. 2015 David Y. Graham Lecture: The First Two Decades Of Eosinophilic Esophagitis-From Acid Reflux To Food Allergy. Am J Gastroenterol. 2016 Jun;111(6):770-6. doi: 10.1038/ajg.2016.136. Epub 2016 Apr 12.
Carlson DA, Hirano I. Narrow-caliber esophagus of eosinophilic esophagitis: difficult to define, resistant to remedy. Gastrointest Endosc. 2016 Jun;83(6):1149-50. doi: 10.1016/j.gie.2016.01.034.
Davis BP, Rothenberg ME. Mechanisms of Disease of Eosinophilic Esophagitis. Annu Rev Pathol. 2016 May 23;11:365-93. doi: 10.1146/annurev-pathol-012615-044241. Epub 2016 Feb 24.
Merkel PA, Manion M, Gopal-Srivastava R, Groft S, Jinnah HA, Robertson D, Krischer JP; Rare Diseases Clinical Research Network. The partnership of patient advocacy groups and clinical investigators in the rare diseases clinical research network. Orphanet J Rare Dis. 2016 May 18;11(1):66. doi: 10.1186/s13023-016-0445-8.
Tkachenko E, Rawson R, La E, Doherty TA, Baum R, Cavagnero K, Miyanohara A, Dohil R, Kurten RC, Aceves SS. Rigid substrate induces esophageal smooth muscle hypertrophy and eosinophilic esophagitis fibrotic gene expression. J Allergy Clin Immunol. 2016 Apr;137(4):1270-1272.e1. doi: 10.1016/j.jaci.2015.09.020. Epub 2015 Nov 2.
Kliewer KL, Venter C, Cassin AM, Abonia JP, Aceves SS, Bonis PA, Dellon ES, Falk GW, Furuta GT, Gonsalves N, Gupta SK, Hirano I, Kagalwalla A, Leung J, Mukkada VA, Spergel JM, Rothenberg ME. Should wheat, barley, rye, and/or gluten be avoided in a 6-food elimination diet?. J Allergy Clin Immunol. 2016 Apr;137(4):1011-1014. doi: 10.1016/j.jaci.2015.10.040. Epub 2015 Dec 24.
Chandramouleeswaran PM, Shen D, Lee AJ, Benitez A, Dods K, Gambanga F, Wilkins BJ, Merves J, Noah Y, Toltzis S, Yearley JH, Spergel JM, Nakagawa H, Malefyt Rd, Muir AB, Wang ML. Preferential Secretion of Thymic Stromal Lymphopoietin (TSLP) by Terminally Differentiated Esophageal Epithelial Cells: Relevance to Eosinophilic Esophagitis (EoE). PLoS One. 2016 Mar 18;11(3):e0150968. doi: 10.1371/journal.pone.0150968. eCollection 2016.
Molina-Infante J, Bredenoord AJ, Cheng E, Dellon ES, Furuta GT, Gupta SK, Hirano I, Katzka DA, Moawad FJ, Rothenberg ME, Schoepfer A, Spechler SJ, Wen T, Straumann A, Lucendo AJ; PPI-REE Task Force of the European Society of Eosinophilic Oesophagitis (EUREOS). Proton pump inhibitor-responsive oesophageal eosinophilia: an entity challenging current diagnostic criteria for eosinophilic oesophagitis. Gut. 2016 Mar;65(3):524-31. doi: 10.1136/gutjnl-2015-310991. Epub 2015 Dec 18.
Watts A, Alexander JA, Gupta SK. Eosinophilic esophagitis: search for noninvasive techniques for long-term monitoring. Gastrointest Endosc. 2016 Feb;83(2):307-8. doi: 10.1016/j.gie.2015.07.006.
Hill DA, Spergel JM. The Immunologic Mechanisms of Eosinophilic Esophagitis. Curr Allergy Asthma Rep. 2016 Feb;16(2):9. doi: 10.1007/s11882-015-0592-3.
Gonsalves N, Furuta GT, Atkins D. Eosinophilic Gastrointestinal Disorders Affect More Than Just the Esophagus. J Pediatr Gastroenterol Nutr. 2016 Jan;62(1):1-2. doi: 10.1097/MPG.0000000000000993.
Rajan J, Newbury RO, Anilkumar A, Dohil R, Broide DH, Aceves SS. Long-term assessment of esophageal remodeling in patients with pediatric eosinophilic esophagitis treated with topical corticosteroids. J Allergy Clin Immunol. 2016 Jan;137(1):147-156.e8. doi: 10.1016/j.jaci.2015.05.045. Epub 2015 Jul 30.
Rawson R, Anilkumar A, Newbury RO, Bafna V, Aquino M, Palmquist J, Hoffman HM, Mueller JL, Dohil R, Broide DH, Aceves SS. The TGFβ1 Promoter SNP C-509T and Food Sensitization Promote Esophageal Remodeling in Pediatric Eosinophilic Esophagitis. PLoS One. 2015 Dec 14;10(12):e0144651. doi: 10.1371/journal.pone.0144651. eCollection 2015.
Furuta GT, Katzka DA. Eosinophilic Esophagitis. N Engl J Med. 2015 Oct 22;373(17):1640-8. doi: 10.1056/NEJMra1502863.
Leung J, Beukema KR, Shen AH. Allergic mechanisms of Eosinophilic oesophagitis. Best Pract Res Clin Gastroenterol. 2015 Oct;29(5):709-720. doi: 10.1016/j.bpg.2015.09.012. Epub 2015 Sep 11.
Spergel JM. An allergist's perspective to the evaluation of Eosinophilic Esophagitis. Best Pract Res Clin Gastroenterol. 2015 Oct;29(5):771-781. doi: 10.1016/j.bpg.2015.06.011. Epub 2015 Jul 8.
Jensen ET, Dellon ES. Environmental and infectious factors in eosinophilic esophagitis. Best Pract Res Clin Gastroenterol. 2015 Oct;29(5):721-729. doi: 10.1016/j.bpg.2015.06.008. Epub 2015 Jul 17.
Cianferoni A, Spergel JM. From genetics to treatment of eosinophilic esophagitis. Curr Opin Allergy Clin Immunol. 2015 Oct;15(5):417-25. doi: 10.1097/ACI.0000000000000200.
Nguyen N, Furuta GT, Menard-Katcher C. Recognition and Assessment of Eosinophilic Esophagitis: The Development of New Clinical Outcome Metrics. Gastroenterol Hepatol (N Y). 2015 Oct;11(10):670-4.
Sodikoff J, Hirano I. Therapeutic strategies in eosinophilic esophagitis: Induction, maintenance and refractory disease. Best Pract Res Clin Gastroenterol. 2015 Oct;29(5):829-839. doi: 10.1016/j.bpg.2015.09.002. Epub 2015 Sep 11.
Mehta P, Furuta GT. Eosinophils in Gastrointestinal Disorders: Eosinophilic Gastrointestinal Diseases, Celiac Disease, Inflammatory Bowel Diseases, and Parasitic Infections. Immunol Allergy Clin North Am. 2015 Aug;35(3):413-37. doi: 10.1016/j.iac.2015.04.003. Epub 2015 Jun 17.
Kia L, Hirano I. Distinguishing GERD from eosinophilic oesophagitis: concepts and controversies. Nat Rev Gastroenterol Hepatol. 2015 Jul;12(7):379-386. doi: 10.1038/nrgastro.2015.75. Epub 2015 May 19.
Eluri S, Dellon ES. Proton pump inhibitor-responsive oesophageal eosinophilia and eosinophilic oesophagitis: more similarities than differences. Curr Opin Gastroenterol. 2015 Jul;31(4):309-15. doi: 10.1097/MOG.0000000000000185.
Benitez AJ, Hoffmann C, Muir AB, Dods KK, Spergel JM, Bushman FD, Wang ML. Inflammation-associated microbiota in pediatric eosinophilic esophagitis. Microbiome. 2015 Jun 1;3:23. doi: 10.1186/s40168-015-0085-6. eCollection 2015.
Rothenberg ME. Molecular, genetic, and cellular bases for treating eosinophilic esophagitis. Gastroenterology. 2015 May;148(6):1143-57. doi: 10.1053/j.gastro.2015.02.002. Epub 2015 Feb 7.
Kochar B, Dellon ES. Management of proton pump inhibitor responsive-esophageal eosinophilia and eosinophilic esophagitis: controversies in treatment approaches. Expert Rev Gastroenterol Hepatol. 2015;9(11):1359-69. doi: 10.1586/17474124.2015.1088384. Epub 2015 Sep 12.
Cianferoni A, Spergel JM, Muir A. Recent advances in the pathological understanding of eosinophilic esophagitis. Expert Rev Gastroenterol Hepatol. 2015;9(12):1501-10. doi: 10.1586/17474124.2015.1094372. Epub 2015 Oct 15.
Moses RG, Similuk M, Hehn A, Duncan R, Pekar M, Gordon-Lipkin E, Acosta MT, Zeltser D, Reynolds-Lallement N, Soorya L, Sahin M, Levy T, Kolevzon A, Buxbaum JD, Berry-Kravis E, Powell CM, Bernstein JA, Tokita M, Seifert BA, Ghosh R, Walkiewicz MA, Thurm A. Genome Sequencing Uncovers Additional Findings in Phelan-McDermid Syndrome. Am J Med Genet B Neuropsychiatr Genet. 2025 Jun 16:e33036. doi: 10.1002/ajmg.b.33036. Epub ahead of print. PMID: 40519070.
Phelan-McDermid syndrome (PMS) is a genetic neurodevelopmental disorder that results from the loss of a small piece of chromosome 22 or variants in the SHANK3 gene. Symptoms of PMS include intellectual disability, autism spectrum disorder, low muscle tone, and absent speech. However, these symptoms can vary widely from person to person, even among those with the same molecular cause.
In this study, researchers used genome sequencing to identify additional molecular diagnoses that may contribute to symptom variability in PMS. The team analyzed genome sequencing and chromosomal microarray in 20 individuals with PMS.
Results revealed a second molecular finding associated with a neurological condition in three participants. Five additional new molecular diagnoses were associated with a clinically actionable secondary or incidental finding. Authors note that this study provides early evidence for the potential use of expanded sequencing among individuals with PMS, even for those without symptoms outside of the expected range.
Chambers N, Heunis TM, Gardner-Lubbe S, Capal JK, Bissell S, Byars AW, Cukier S, Davis PE, Flinn J, Gipson TT, Kingswood JC, Kumm AJ, Schoeters E, Smith C, Srivastava S, Takei M, Vanclooster S, van Eeghen AM, Waltereit R, Krueger DA, Sahin M, De Waele L, Jansen AC, de Vries PJ. Validation of the self-report quantified Tuberous Sclerosis Complex-Associated Neuropsyciatric Disorders Checklist (TAND-SQ). Orphanet J Rare Dis. 2025 Jun 13;20(1):304. doi: 10.1186/s13023-025-03642-2.
Kim AY, Yehia L, Eng C. Genomic diversity in functionally relevant genes modifies neurodevelopmental versus neoplastic risks in individuals with germline PTEN variants. NPJ Genom Med. 2025 May 20;10(1):43. doi: 10.1038/s41525-025-00495-3. PMID: 40394016; PMCID: PMC12092801.
PTEN hamartoma tumor syndrome (PHTS) is a spectrum of disorders caused by mutations in the PTEN gene, which typically suppresses formation of tumors. Individuals with PHTS have increased risks of cancer and neurodevelopmental disorders, including autism spectrum disorder (ASD). Not much is known about why patients with PHTS are at increased risk for these seemingly unrelated outcomes.
In this study, researchers explored the relationship between genomic diversity and neurodevelopmental versus cancer risks in individuals with PHTS. The team analyzed the genotypes of 376 individuals with PHTS and grouped them according to clinical phenotypes of neurodevelopmental disorders (including ASD) and non-neurodevelopmental disorders (including cancer).
In the neurodevelopmental disorders group, results revealed an increased accumulation of homozygous common variants in genes involved in inflammatory processes. In the ASD group, researchers also found an increased accumulation of homozygous common variants in genes involved in differentiation and chromatin structure regulation. However, in the cancer group, the team found an increased accumulation of homozygous ultra-rare variants in genes modulating cell death.
Authors note that these findings suggest a new concept of genomic diversity as a modifier of neurodevelopmental and malignant phenotypes in those with PHTS. Results also demonstrate potential clinical utility—especially for neurodevelopmental phenotypes—for better PHTS patient management.
Dhawan A, Baitamouni S, Liu D, Yehia L, Anthony K, McCarther A, Tischkowitz M, MacFarland SP, Ngeow J, Hoogerbrugge N, Eng C. Cancer and Overgrowth Manifestations of PTEN Hamartoma Tumor Syndrome: Management Recommendations from the International PHTS Consensus Guidelines Working Group. Clin Cancer Res. 2025 May 1;31(9):1754-1765. doi: 10.1158/1078-0432.CCR-24-3819.
Silver H, Greenberg R, Siper PM, Zweifach J, Soufer R, Sahin M, Berry-Kravis E, Soorya LV, Thurm A, Bernstein JA, Kolevzon A, Grice DE, Buxbaum JD, Levy T. Protein-truncating variants and deletions of SHANK2 are associated with autism spectrum disorder and other neurodevelopmental concerns. J Neurodev Disord. 2025 Apr 30;17(1):25. doi: 10.1186/s11689-025-09600-0.
Yehia L, Plitt G, Tushar AM, Liu D, Joo J, Ni Y, Patil S, Eng C. Extended spectrum of cancers in PTEN hamartoma tumor syndrome. NPJ Precis Oncol. 2025 Mar 6;9(1):61. doi: 10.1038/s41698-025-00847-3.
Winden KD, Ruiz JF, Sahin M. Construction destruction: Contribution of dyregulated proteostasis to neurodevelopmental disorders. Curr Opin Neurobiol. 2025 Feb;90:102934. doi: 10.1016/j.conb.2024.102934. Epub 2024 Nov 28.
Winden KD, Gisser I, Sahin M. Using cortical organoids to understand the pathogenesis of malformations of cortical development. Front Neurosci. 2025 Jan 15;18:1522652. doi: 10.3389/fnins.2024.1522652. eCollection 2024.
Yang Z, Teaney NA, Buttermore ED, Sahin M, Afshar-Saber W. Harnessing the potential of human induced pluripotent stem cells, functional assays and machine learning for neurodevelopmental disorders. Front Neurosci. 2025 Jan 8;18:1524577. doi: 10.3389/fnins.2024.1524577. PMID: 39844857; PMCID: PMC11750789.
Neurodevelopmental disorders are associated with delays in brain development and a spectrum of impairments that can lead to lifelong disability and even mortality. Although these disorders affect 4.7% of the global population, there are few biomarkers for accurate diagnosis or medications for effective treatment. Human-induced pluripotent stem cells (hiPSCs) are a promising tool for modeling neurodevelopmental disorders, providing new opportunities to understand mechanisms driving these disorders in human neurons.
In this review, researchers compare two- and three-dimensional hiPSC formats for disease modeling. Authors also discuss the applications of functional assays and offer insights on incorporating machine learning into hiPSC-based research and drug screening for neurodevelopmental disorders. Authors note that these tools present unprecedented opportunities to advance the neurodevelopmental disorder research process.
Frazier TW, Busch RM, Klaas P, Lachlan K, Jeste S, Kolevzon A, Loth E, Harris J, Pepper T, Anthony K, Graglia JM, Helde K, Delagrammatikas C, Bedrosian-Sermone S, Smith-Hicks C, Sahin M, Youngstrom EA, Eng C, Chetcuti L, Hardan AY, Uljarevic M. Remote monitoring of social attention in neurogenetic syndromes and idiopathic neurodevelopmental disability. Autism Res. 2024 Dec 6. doi: 10.1002/aur.3290. Epub ahead of print. PMID: 39643599.
Neurodevelopmental genetic syndromes are conditions that affect the development of brain function. Many individuals with these syndromes experience altered social attention that can impact their ability to accurately perceive social information in their world.
In this study, researchers evaluated remote monitoring of social attention in children, adolescents, and adults with a wide range of neurodevelopmental outcomes. Participants included individuals with three genetic syndromes (PTEN hamartoma tumor syndrome, Malan syndrome, and SYNGAP1-related disorder), a mixed group of other neurodevelopmental genetic syndromes, and individuals with a range of idiopathic neurodevelopmental disorders, as well as neurotypical siblings and unrelated controls. Each participant completed a four-minute social attention paradigm via webcam.
Results show that social attention measures had good scale and test-retest reliability, with the exception of measures of non-social preference and face-specific processing. Findings demonstrate that remote monitoring of social attention may be useful for characterizing phenotypic profiles and tracking the natural history of distinct neurodevelopmental genetic syndromes and idiopathic neurodevelopmental disorders, as well as identifying autism spectrum disorder in patients with neurodevelopmental genetic syndromes. Authors note that global social attention and several distinct social attention measures may also be useful outcomes for future clinical trials.
Farach LS, Richard MA, Wulsin AC, Bebin EM, Krueger DA, Sahin M, Porter BE, McPherson TO, Peters JM, O'Kelley S, Taub KS, Rajaraman R, Randle SC, McClintock WM, Koenig MK, Frost MD, Werner K, Nolan DA, Wong M, Cutter G, Northrup H, Au KS; PREVeNT Study Group. Drug-Resistant Epilepsy in Tuberous Sclerosis Complex Is Associated With TSC2 Genotype: More Findings From the Preventing Epilepsy Using Vigatrin (PREVeNT) Trial. Pediatr Neurol. 2024 Oct;159:62-71. doi: 10.1016/j.pediatrneurol.2024.06.012. Epub 2024 Jul 4.
Srivastava S, Cole JJ, Cohen JS, Chopra M, Smith HS, Deardorff MA, Pedapati E, Corner B, Anixt JS, Jeste S, Sahin M, Gurnett CA, Campbell CA. Survey of the Landscape of Society Practice Guidelines for Genetic Testing of Neurodevelopmental Disorders. Ann Neurol. 2024 Sep 25. doi: 10.1002/ana.27045. Epub ahead of print. PMID: 39319594.
Neurodevelopmental disorders are a spectrum of conditions that affect how the brain functions. These disorders can impact many different areas of childhood development, including motor, problem solving, social-communication, and adaptive skills. Genetic testing of patients with neurodevelopmental disorders is critical for diagnosis, medical management, and access to precision therapies. However, the creation and implementation of professional society practice guidelines for genetic testing can be challenging due to the rapid evolution of approaches.
In this review, authors assessed the current state of United States professional societies' guidelines for genetic testing of neurodevelopmental disorders. The team focused on disorders including unexplained global developmental delay, intellectual disability, autism spectrum disorder, and cerebral palsy. Authors describe several shortcomings of current guidelines and express the need for a unified, frequently updated, and easily accessible cross-specialty society guideline.
Gluckman J, Levy T, Friedman K, Garces F, Filip-Dhima R, Quinlan A, Iannotti I, Pekar M, Hernandez AL, Nava MT, Kravets E, Siegel A, Bernstein JA, Berry-Kravis E, Powell CM, Soorya LV, Thurm A, Srivastava S, Buxbaum JD, Sahin M, Kolevzon A, Gelb BD. Aortic Root Dilation and Genotype Associations in Phelan-McDermid Syndrome. Am J Med Genet A. 2024 Sep 11:e63872. doi: 10.1002/ajmg.a.63872. Epub ahead of print. PMID: 39257296.
Phelan-McDermid syndrome (PMS) is a genetic neurodevelopmental disorder that results from the loss of a small piece of chromosome 22. While many features of PMS are well-understood, less is known about cardiovascular abnormalities.
In this study, researchers evaluated the prevalence and risk of aortic root dilation (ARD) in patients with PMS. Among 59 individuals with PMS, the team analyzed echocardiographic and genetic reports for aortic root measurements and genetic variant data.
Results reveal that eight participants had ARD, which was associated with larger chromosome 22 deletions. Participants with ARD also had significantly more genes deleted on chromosome 22 than participants without ARD. Authors note that these results could help identify individuals with PMS who are at higher risk for ARD.
Ahtam B, Yun HJ, Vyas R, Pienaar R, Wilson JH, Goswami CP, Berto LF, Warfield SK, Sahin M, Grant PE, Peters JM, Im K. Morphological Features of Language Regions in Individuals with Tuberous Sclerosis Complex. J Autism Dev Disord. 2024 Aug;54(8):3155-3175. doi: 10.1007/s10803-023-06004-8. Epub 2023 May 24. Erratum in: J Autism Dev Disord. 2024 Mar;54(3):1232. doi: 10.1007/s10803-023-06098-0. PMID: 37222965.
Tuberous sclerosis complex (TSC) is a genetic condition in which typically benign tumors affect multiple organs including the brain, kidneys, heart, lungs, eyes, and skin. Many individuals with TSC also experience delay in several aspects of development, including language.
In this structural brain MRI study, researchers examined the morphological features of cortical language regions in individuals with TSC. Participants included seven individuals with TSC and comorbid autism spectrum disorder (ASD), 13 with TSC but no ASD, 10 with ASD-only, and 29 typically developing controls.
Results suggest that comorbid ASD in TSC as well as tuber load in TSC is associated with changes in the morphometry of language regions. Authors note that future studies with larger sample sizes are needed to confirm these findings.
Brown JA, Faley SL, Judge M, Ward P, Ihrie RA, Carson R, Armstrong L, Sahin M, Wikswo JP, Ess KC, Neely MD. Rescue of impaired blood-brain barrier in tuberous sclerosis complex patient derived neurovascular unit. J Neurodev Disord. 2024 May 23;16(1):27. doi: 10.1186/s11689-024-09543-y. PMID: 38783199; PMCID: PMC11112784.
Tuberous sclerosis complex (TSC) is a genetic condition that affects many organs and can cause benign tumors in the skin, kidney, brain, heart, eyes, lungs, and other organs. The most severe symptoms—including seizures, intellectual disability, autism, and behavioral problems—result from complications in the central nervous system. Although these neurological complications are well-understood, less is known about how the genetic mutations that cause TSC might affect different components of the brain, including the blood-brain barrier.
In this study, researchers examined the function of the blood-brain barrier in TSC. The team created TSC patient-specific brain tissue models to explore how mutations in the TSC2 gene affect the blood-brain barrier.
Results show altered function of a blood-brain barrier generated from TSC2 mutant cells, which can improve with treatment of the drug rapamycin or replacement of mutant cells with astrocytes (glial cells in the brain) that do not carry the mutation. Authors note that these findings demonstrate the importance of their methods in ongoing research for TSC and other neurogenetic disorders.
Levy T, Gluckman J, Siper PM, Halpern D, Zweifach J, Filip-Dhima R, Holder JL Jr, Trelles MP, Johnson K, Bernstein JA, Berry-Kravis E, Powell CM, Soorya LV, Thurm A, Buxbaum JD, Sahin M, Kolevzon A, Srivastava S; Developmental Synaptopathies Consortium. Clinical, genetic, and cognitive correlates of seizure occurrences in Phelan-McDermid syndrome. J Neurodev Disord. 2024 May 10;16(1):25. doi: 10.1186/s11689-024-09541-0.
Dhawan A, Baitamouni S, Liu D, Busch R, Klaas P, Frazier TW, Srivastava S, Parikh S, Hsich GE, Friedman NR, Ritter DM, Hardan AY, Martinez-Agosto JA, Sahin M, Eng C. Exploring the neurological features of individuals with germline PTEN variants: A multicenter study. Ann Clin Transl Neurol. 2024 May;11(5):1301-1309. doi: 10.1002/acn3.52046. Epub 2024 Mar 19.
Richard MA, Lupo PJ, Ehli EA, Sahin M, Krueger DA, Wu JY, Bebin EM, Au KS, Northrup H, Farach LS; TACERN Study Group. Common epilepsy variants from the general population are not associated with epilepsy among individuals with tuberous sclerosis complex. Am J Med Genet A. 2024 Jun;194(6):e63569. doi: 10.1002/ajmg.a.63569. Epub 2024 Feb 17.
Macaluso M, Rothenberg ME, Ferkol T, Kuhnell P, Kaminski HJ, Kimberlin DW, Benatar M, Chehade M; Principal Investigators of the Rare Diseases Clinical Research Network – Cycle 4. Impact of the COVID-19 Pandemic on People Living With Rare Diseases and Their Families: Results of a National Survey. JMIR Public Health Surveill. 2024 Feb 14;10:e48430. doi: 10.2196/48430.
Afshar-Saber W, Teaney NA, Winden KD, Jumo H, Shi X, McGinty G, Hubbs J, Chen C, Tokatly Latzer I, Gasparoli F, Ebrahimi-Fakhari D, Buttermore ED, Roullet JB, Pearl PL, Sahin M. ALDH5A1-deficient iPSC-derived excitatory and inhibitory neurons display cell type specific alterations. Neurobiol Dis. 2024 Jan;190:106386. doi: 10.1016/j.nbd.2023.106386. Epub 2023 Dec 16.
Brown JA, Faley SL, Judge M, Ward P, Ihrie RA, Carson R, Armstrong L, Sahin M, Wikswo JP, Ess KC, Neely MD. Rescue of Impaired Blood-Brain Barrier in Tuberous Sclerosis Complex Patient Derived Neurovascular Unit. bioRxiv. 2023 Dec 16:2023.12.15.571738. doi: 10.1101/2023.12.15.571738.
Eng C, Kim A, Yehia L. Genomic diversity in functionally relevant genes modifies neurodevelopmental versus neoplastic risks in individuals with germline PTEN variants. Res Sq. 2023 Dec 14:rs.3.rs-3734368. doi: 10.21203/rs.3.rs-3734368/v1.
Clements CC, Ascunce K, Nelson CA. In Context: A Developmental Model of Reward Processing, With Implications for Autism and Sensitive Periods. J Am Acad Child Adolesc Psychiatry. 2023 Nov;62(11):1200-1216. doi: 10.1016/j.jaac.2022.07.861. Epub 2022 Nov 3.
Heunis TM, Chambers N, Vanclooster S, Bissell S, Byars AW, Capal JK, Cukier S, Davis PE, de Vries MC, De Waele L, Flinn J, Gardner-Lubbe S, Gipson T, Kingswood JC, Krueger DA, Kumm AJ, Sahin M, Schoeters E, Smith C, Srivastava S, Takei M, van Eeghen AM, Waltereit R, Jansen AC, de Vries PJ. Development and Feasibility of the Self-Report Quantified Tuberous Sclerosis Complex-Associated Neuropsychiatric Disorders Checklist (TAND-SQ). Pediatr Neurol. 2023 Oct;147:101-123. doi: 10.1016/j.pediatrneurol.2023.07.001. Epub 2023 Jul 7. PMID: 37598571
Tuberous sclerosis complex (TSC) is a genetic condition in which typically benign tumors affect multiple organs including the brain, kidneys, heart, lungs, eyes, and skin. TSC-associated neuropsychiatric disorders (TAND) include difficulties at the behavioral, psychiatric, intellectual, academic, neuropsychologic, and psychosocial levels. Although TAND are often present in individuals with TSC, they are also underidentified and undertreated.
In this study, researchers developed a self-report quantified TAND Checklist (TAND-SQ). The team conducted feasibility and acceptability testing of the TAND-SQ Checklist with 23 technical experts from the TAND consortium and 58 caregivers and individuals with TSC.
The resulting Checklist can be completed by caregivers or individuals with TSC and used to quantify TAND difficulties. Authors state that next steps include further validation of the checklist and development of a smartphone application.
Srivastava S, Sahin M, Buxbaum JD, Berry-Kravis E, Soorya LV, Thurm A, Bernstein JA, Asante-Otoo A, Bennett WE Jr, Betancur C, Brickhouse TH, Passos Bueno MR, Chopra M, Christensen CK, Cully JL, Dies K, Friedman K, Gummere B, Holder JL Jr, Jimenez-Gomez A, Kerins CA, Khan O, Kohlenberg T, Lacro RV, Levi LA, Levy T, Linnehan D, Eva L, Moshiree B, Neumeyer A, Paul SM, Phelan K, Persico A, Rapaport R, Rogers C, Saland J, Sethuram S, Shapiro J, Tarr PI, White KM, Wickstrom J, Williams KM, Winrow D, Wishart B, Kolevzon A. Updated consensus guidelines on the management of Phelan-McDermid syndrome. Am J Med Genet A. 2023 Jul 1. doi: 10.1002/ajmg.a.63312. Epub ahead of print. PMID: 37392087
Phelan–McDermid syndrome (PMS) is a genetic condition caused by the deletion of a small portion of chromosome 22 or a mutation in the SHANK3 gene resulting in a wide range of neurodevelopmental and systemic characteristics. The first guidelines for assessment and monitoring in individuals with PMS were published in 2014. Due to recent studies and investigations, knowledge about PMS has since grown significantly.
In this study, researchers aimed to update clinical management guidelines for PMS based on the latest knowledge. A taskforce of clinical experts in PMS and representatives from the parent community collaborated to produce specialty-specific guidelines—including genetics, neurology, neurodevelopment, gastroenterology, primary care, physiatry, nephrology, endocrinology, cardiology, gynecology, and dentistry.
These updated guidelines allow for improved assessment and monitoring of individuals with PMS. Authors highlight several areas for future research with plans to update the guidelines as new knowledge becomes available.
Morgan FC, Yehia L, McDonald C, Martinez-Agosto JA, Hardan AY, Tamburro J, Sahin M, Bayart C, Eng C; Developmental Synaptopathies Consortium. Characterizing dermatologic findings among patients with PTEN hamartoma tumor syndrome: Results of a multicenter cohort study. J Am Acad Dermatol. 2023 Jul;89(1):90-98. doi: 10.1016/j.jaad.2022.01.045. Epub 2022 Feb 7.
Levine A, Davis P, Zhang B, Peters J, Filip-Dhima R, Warfield SK, Prohl A, Capal J, Krueger D, Bebin EM, Northrup H, Wu JY, Sahin M; TACERN Study Group. Epilepsy Severity Is Associated With Head Circumference and Growth Rate in Infants With Tuberous Sclerosis Complex. Pediatr Neurol. 2023 Jul;144:26-32. doi: 10.1016/j.pediatrneurol.2023.03.015. Epub 2023 Mar 29.
Patterson AM, O'Boyle M, VanNoy GE, Dies KA. Emerging roles and opportunities for rare disease patient advocacy groups. Ther Adv Rare Dis. 2023 Apr 24;4:26330040231164425. doi: 10.1177/26330040231164425. eCollection 2023 Jan-Dec.
Yehia L, Plitt G, Tushar AM, Joo J, Burke CA, Campbell SC, Heiden K, Jin J, Macaron C, Michener CM, Pederson HJ, Radhakrishnan K, Shin J, Tamburro J, Patil S, Eng C. Longitudinal Analysis of Cancer Risk in Children and Adults With Germline PTEN Variants. JAMA Netw Open. 2023 Apr 3;6(4):e239705. doi: 10.1001/jamanetworkopen.2023.9705.
Yehia L, Heald B, Eng C. Clinical Spectrum and Science Behind the Hamartomatous Polyposis Syndromes. Gastroenterology. 2023 Apr;164(5):800-811. doi: 10.1053/j.gastro.2023.01.026. Epub 2023 Jan 28.
Applequist J, Burroughs C, Merkel PA, Rothenberg M, Trapnell B, Desnick R, Sahin M, Krischer J. Direct-to-Consumer Recruitment Methods via Traditional and Social Media to Aid in Research Accrual for Clinical Trials for Rare Diseases: Comparative Analysis Study. J Med Internet Res. 2023 Mar 14;25:e39262. doi: 10.2196/39262.
Cohen AL, Kroeck MR, Wall J, McManus P, Ovchinnikova A, Sahin M, Krueger DA, Bebin EM, Northrup H, Wu JY, Warfield SK, Peters JM, Fox MD; Tuberous Sclerosis Complex Autism Center of Excellence Network Study Group. Tubers Affecting the Fusiform Face Area Are Associated with Autism Diagnosis. Ann Neurol. 2023 Mar;93(3):577-590. doi: 10.1002/ana.26551. Epub 2022 Nov 30. PMID: 36394118; PMCID: PMC9974824.
Tuberous sclerosis complex (TSC) is a genetic condition in which typically benign tumors affect multiple organs. TSC is associated with tubers—tumors that form in the brain—and a high incidence of autism spectrum disorder (ASD).
In this study, researchers explored the relationship between location of brain tubers and ASD diagnosis. The team began by determining tuber locations for 115 TSC patients with and without ASD. Next, researchers tested for associations between ASD diagnosis and tuber burden within the whole brain and specific locations relevant to ASD. Finally, they created a map of the data to calculate the risk of ASD.
Results show that tubers involving the right fusiform face area (FFA) were associated with a 3.7-fold increased risk of developing ASD. Authors note that this strong association highlights a potential causal mechanism for developing autism in TSC, which may help guide more general research on ASD symptoms.
Busch RM, Frazier Ii TW, Sonneborn C, Hogue O, Klaas P, Srivastava S, Hardan AY, Martinez-Agosto JA, Sahin M, Eng C. Longitudinal neurobehavioral profiles in children and young adults with PTEN hamartoma tumor syndrome and reliable methods for assessing neurobehavioral change. J Neurodev Disord. 2023 Jan 14;15(1):3. doi: 10.1186/s11689-022-09468-4. PMID: 36641436; PMCID: PMC9840250.
PTEN hamartoma tumor syndrome (PHTS) is a spectrum of disorders caused by mutations in the PTEN gene, which typically suppresses formation of tumors. In addition to its role in cancer, PTEN plays crucial roles in brain function. Individuals with PHTS show distinct neurobehavioral profiles, suggesting primary disruption of frontal lobe systems. More severe cognitive deficits are seen in individuals with associated autism spectrum disorder (ASD) that also extend to other areas of neurobehavioral function, such as adaptive behavior and sensory deficits. In this study, researchers aimed to characterize longitudinal neurobehavioral profiles in individuals with PHTS. Ninety-two children and young adults with PHTS and/or ASD completed two to three neurobehavioral evaluations over a two-year time period. The team used spaghetti plots and linear mixed effects models to visualize individual patient profiles and group trends, examining differences in cognitive and behavioral test scores over time. Results suggest that neurobehavioral characteristics observed in individuals with PHTS remain relatively stable over time, even in those with ASD. Reliable change indices and standardized regression-based change scores were calculated and provided in an easy-to-use Excel calculator that can be used in future research to examine patient outcomes at the individual level and inform intervention strategies.
Srivastava S, Jo B, Zhang B, Frazier T, Gallagher AS, Peck F, Levin AR, Mondal S, Li Z, Filip-Dhima R, Geisel G, Dies KA, Diplock A, Eng C, Hanna R, Sahin M, Hardan A; Developmental Synaptopathies Consortium. A randomized controlled trial of everolimus for neurocognitive symptoms in PTEN hamartoma tumor syndrome. Hum Mol Genet. 2022 Oct 10;31(20):3393-3404. doi: 10.1093/hmg/ddac111. PMID: 35594551.
Breen MS, Fan X, Levy T, Pollak RM, Collins B, Osman A, Tocheva AS, Sahin M, Berry-Kravis E, Soorya L, Thurm A, Powell CM, Bernstein JA, Kolevzon A, Buxbaum JD; Developmental Synaptopathies Consortium. Large 22q13.3 deletions perturb peripheral transcriptomic and metabolomic profiles in Phelan-McDermid syndrome. HGG Adv. 2022 Sep 26;4(1):100145. doi: 10.1016/j.xhgg.2022.100145. eCollection 2023 Jan 12.
Chopra M, Modi ME, Dies KA, Chamberlin NL, Buttermore ED, Brewster SJ, Prock L, Sahin M. GENE TARGET: A framework for evaluating Mendelian neurodevelopmental disorders for gene therapy. Mol Ther Methods Clin Dev. 2022 Aug 29;27:32-46. doi: 10.1016/j.omtm.2022.08.007. eCollection 2022 Dec 8.
Siper PM, Rowe MA, Guillory SB, Rouhandeh AA, George-Jones JL, Tavassoli T, Lurie S, Zweifach J, Weissman J, Foss-Feig J, Halpern D, Trelles MP, Mulhern MS, Brittenham C, Gordon J, Zemon V, Buxbaum JD, Kolevzon A. Visual Evoked Potential Abnormalities in Phelan-McDermid Syndrome. J Am Acad Child Adolesc Psychiatry. 2022 Apr;61(4):565-574.e1. doi: 10.1016/j.jaac.2021.07.006. Epub 2021 Jul 22. PMID: 34303785; PMCID: PMC8782912.
Yehia L, Ni Y, Sadler T, Frazier TW, Eng C.. Distinct metabolic profiles associated with autism spectrum disorder versus cancer in individuals with germline PTEN mutations. NPJ Genom Med. 2022 Mar 3;7(1):16. doi: 10.1038/s41525-022-00289-x. PMID: 35241692; PMCID: PMC8894426.
Levy T, Foss-Feig JH, Betancur C, Siper PM, Trelles-Thorne MDP, Halpern D, Frank Y, Lozano R, Layton C, Britvan B, Bernstein JA, Buxbaum JD, Berry-Kravis E, Powell CM, Srivastava S, Sahin M, Soorya L, Thurm A, Kolevzon A; Developmental Synaptopathies Consortium. Strong evidence for genotype-phenotype correlations in Phelan-McDermid syndrome: results from the developmental synaptopathies consortium. Hum Mol Genet. 2022 Feb 21;31(4):625-637. doi: 10.1093/hmg/ddab280. PMID: 34559195; PMCID: PMC8863417.
Guillory SB, Baskett VZ, Grosman HE, McLaughlin CS, Isenstein EL, Wilkinson E, Weissman J, Britvan B, Trelles MP, Halpern DB, Buxbaum JD, Siper PM, Wang AT, Kolevzon A, Foss-Feig JH. Social visual attentional engagement and memory in Phelan-McDermid syndrome and autism spectrum disorder: a pilot eye tracking study. J Neurodev Disord. 2021 Dec 4;13(1):58. doi: 10.1186/s11689-021-09400-2. PMID: 34863106.
Cable J, Purcell RH, Robinson E, Vorstman JAS, Chung WK, Constantino JN, Sanders SJ, Sahin M, Dolmetsch RE, Shah BM, Thurm A, Martin CL, Bearden CE, Mulle JG. Harnessing rare variants in neuropsychiatric and neurodevelopment disorders-a Keystone Symposia report. Ann N Y Acad Sci. 2021 Dec;1506(1):5-17. doi: 10.1111/nyas.14658. Epub 2021 Aug 2. PMID: 34342000; PMCID: PMC8688183.
Capal JK, Williams ME, Pearson DA, Kissinger R, Horn PS, Murray D, Currans K, Kent B, Bebin M, Northrup H, Wu JY, Sahin M, Krueger DA; TACERN Study Group. Profile of Autism Spectrum Disorder in Tuberous Sclerosis Complex: Results from a Longitudinal, Prospective, Multisite Study. Ann Neuro. 2021 Dec;90(6):874-886. doi: 10.1002/ana.26249. Epub 2021 Oct 29. PMID: 34668231; PMCID: PMC8639652.
Srivastava S, Condy E, Carmody E, Filip-Dhima R, Kapur K, Bernstein JA, Berry-Kravis E, Powell CM, Soorya L, Thurm A, Buxbaum JD, Sahin M, Kolevzon AL; Developmental Synaptopathies Consortium. Parent-reported measure of repetitive behavior in Phelan-McDermid syndrome. J Neurodev Disord. 2021 Nov 5;13(1):53. doi: 10.1186/s11689-021-09398-7. PMID: 34740315; PMCID: PMC8570010.
de Vries PJ, Leclezio L, Gardner-Lubbe S, Krueger D, Sahin M, Sparagana S, De Waele L, Jansen A. Multivariate data analysis identifies natural clusters of Tuberous Sclerosis Complex Associated Neuropsychiatric Disorders (TAND). Orphanet J Rare Dis. 2021 Oct 24;16(1):447. doi: 10.1186/s13023-021-02076-w. PMID: 34689816; PMCID: PMC8543869.
Uljarević M, Frazier TW, Rached G, Busch RM, Klaas P, Srivastava S, Martinez-Agosto JA, Sahin M, Eng C, Hardan AY; Developmental Synaptopathies Consortium. Toward better characterization of restricted and repetitive behaviors in individuals with germline heterozygous PTEN mutations. Am J Med Genet A. 2021 Aug 23. doi: 10.1002/ajmg.a.62458. Online ahead of print.
Steele M, Uljarević M, Rached G, Frazier TW, Phillips JM, Libove RA, Busch RM, Klaas P, Martinez-Agosto JA, Srivastava S, Eng C, Sahin M, Hardan AY. Psychiatric Characteristics Across Individuals With PTEN Mutations. Front Psychiatry. 2021 Aug 17;12:672070. doi: 10.3389/fpsyt.2021.672070. eCollection 2021.
Ihnen SKZ, Capal JK, Horn PS, Griffith M, Sahin M, Bebin EM, Wu JY, Northrup H, Krueger DA; TACERN study group. Epilepsy Is Heterogeneous in Early-Life Tuberous Sclerosis Complex. Pediatr Neurol. 2021 Oct;123:1-9. doi: 10.1016/j.pediatrneurol.2021.06.012. Epub 2021 Jul 6.
Anderson NC, Chen PF, Meganathan K, Afshar Saber W, Petersen AJ, Bhattacharyya A, Kroll KL, Sahin M; Cross-IDDRC Human Stem Cell Working Group. Balancing serendipity and reproducibility: Pluripotent stem cells as experimental systems for intellectual and developmental disorders. Stem Cell Reports. 2021 Jun 8;16(6):1446-1457. doi: 10.1016/j.stemcr.2021.03.025. Epub 2021 Apr 15. PMID: 33861989; PMCID: PMC8190574.
Mariscal MG, Berry-Kravis E, Buxbaum JD, Ethridge LE, Filip-Dhima R, Foss-Feig JH, Kolevzon A, Modi ME, Mosconi MW, Nelson CA, Powell CM, Siper PM, Soorya L, Thaliath A, Thurm A, Zhang B, Sahin M, Levin AR; Developmental Synaptopathies Consortium. Shifted phase of EEG cross-frequency coupling in individuals with Phelan-McDermid syndrome. Mol Autism. 2021 Apr 28;12(1):29. doi: 10.1186/s13229-020-00411-9.
Cohen AL, Mulder BPF, Prohl AK, Soussand L, Davis P, Kroeck MR, McManus P, Gholipour A, Scherrer B, Bebin EM, Wu JY, Northrup H, Krueger DA, Sahin M, Warfield SK, Fox MD, Peters JM; Tuberous Sclerosis Complex Autism Center of Excellence Network Study Group. Tuber Locations Associated with Infantile Spasms Map to a Common Brain Network. Ann Neurol. 2021 Apr;89(4):726-739. doi: 10.1002/ana.26015. Epub 2021 Jan 21.
Uljarević M, Frazier TW, Rached G, Busch RM, Klaas P, Srivastava S, Martinez-Agosto JA, Sahin M, Eng C, Hardan AY; Developmental Synaptopathies Consortium. Brief Report: Role of Parent-Reported Executive Functioning and Anxiety in Insistence on Sameness in Individuals with Germline PTEN Mutations. J Autism Dev Disord. 2021 Feb 17. doi: 10.1007/s10803-021-04881-5. Online ahead of print.
Jia M, Sangwan N, Tzeng A, Eng C.. Interplay Between Class II HLA Genotypes and the Microbiome and Immune Phenotypes in Individuals With PTEN Hamartoma Tumor Syndrome. JCO Precis Oncol. 2021 Feb 9;5:PO.20.00374. doi: 10.1200/PO.20.00374. PMID: 34250407; PMCID: PMC8232567.
Hardan AY, Jo B, Frazier TW, Klaas P, Busch RM, Dies KA, Filip-Dhima R, Snow AV, Eng C, Hanna R, Zhang B, Sahin M. A randomized double-blind controlled trial of everolimus in individuals with PTEN mutations: Study design and statistical considerations. Contemp Clin Trials Commun. 2021 Feb 6;21:100733. doi: 10.1016/j.conctc.2021.100733. eCollection 2021 Mar.
Frazier TW, Jaini R, Busch RM, Wolf M, Sadler T, Klaas P, Hardan AY, Martinez-Agosto JA, Sahin M, Eng C; Developmental Synaptopathies Consortium. Cross-level analysis of molecular and neurobehavioral function in a prospective series of patients with germline heterozygous PTEN mutations with and without autism. Mol Autism. 2021 Jan 28;12(1):5. doi: 10.1186/s13229-020-00406-6.
Farach LS, Richard MA, Lupo PJ, Sahin M, Krueger DA, Wu JY, Bebin EM, Au KS, Northrup H; TACERN Study Group. Epilepsy Risk Prediction Model for Patients With Tuberous Sclerosis Complex. Pediatr Neurol. 2020 Dec;113:46-50. doi: 10.1016/j.pediatrneurol.2020.07.015. Epub 2020 Jul 29.
Shao DD, Achkar CM, Lai A, Srivastava S, Doan RN, Rodan LH, Chen AY; Brain Development Study Group, Poduri A, Yang E, Walsh CA. Polymicrogyria is Associated With Pathogenic Variants in PTEN. Ann Neurol. 2020 Dec;88(6):1153-1164. doi: 10.1002/ana.25904. Epub 2020 Oct 8.
Sahin M, Sweeney JA, Jones SR. Editorial: Biomarkers to Enable Therapeutics Development in Neurodevelopmental Disorders. Front Integr Neurosci. 2020 Nov 12;14:616641. doi: 10.3389/fnint.2020.616641. PMID: 33262695; PMCID: PMC7686575.
Nariai H, Hussain SA, Bernardo D, Motoi H, Sonoda M, Kuroda N, Asano E, Nguyen JC, Elashoff D, Sankar R, Bragin A, Staba RJ, Wu JY. Scalp EEG interictal high frequency oscillations as an objective biomarker of infantile spasms. Clin Neurophysiol. 2020 Nov;131(11):2527-2536. doi: 10.1016/j.clinph.2020.08.013. Epub 2020 Sep 3.
Yehia L, Eng C. PTEN hamartoma tumour syndrome: what happens when there is no PTEN germline mutation?. Hum Mol Genet. 2020 Oct 20;29(R2):R150-R157. doi: 10.1093/hmg/ddaa127.
Gergoudis K, Weinberg A, Templin J, Farmer C, Durkin A, Weissman J, Siper P, Foss-Feig J, Del Pilar Trelles M, Bernstein JA, Buxbaum JD, Berry-Kravis E, Powell CM, Sahin M, Soorya L, Thurm A, Kolevzon A; Developmental Synaptopathies Consortium. Psychometric Study of the Social Responsiveness Scale in Phelan-McDermid Syndrome. Autism Res. 2020 Aug;13(8):1383-1396. doi: 10.1002/aur.2299. Epub 2020 May 14.
Bassell J, Srivastava S, Prohl AK, Scherrer B, Kapur K, Filip-Dhima R, Berry-Kravis E, Soorya L, Thurm A, Powell CM, Bernstein JA, Buxbaum JD, Kolevzon A, Warfield SK, Sahin M; Developmental Synaptopathies Consortium. Diffusion Tensor Imaging Abnormalities in the Uncinate Fasciculus and Inferior Longitudinal Fasciculus in Phelan-McDermid Syndrome. Pediatr Neurol. 2020 May;106:24-31. doi: 10.1016/j.pediatrneurol.2020.01.006. Epub 2020 Jan 31.
Scherrer B, Prohl AK, Taquet M, Kapur K, Peters JM, Tomas-Fernandez X, Davis PE, M Bebin E, Krueger DA, Northrup H, Y Wu J, Sahin M, Warfield SK. The Connectivity Fingerprint of the Fusiform Gyrus Captures the Risk of Developing Autism in Infants with Tuberous Sclerosis Complex. Cereb Cortex. 2020 Apr 14;30(4):2199-2214. doi: 10.1093/cercor/bhz233.
Karimi D, Peters JM, Ouaalam A, Prabhu SP, Sahin M, Krueger DA, Kolevzon A, Eng C, Warfield SK, Gholipour A. LEARNING TO DETECT BRAIN LESIONS FROM NOISY ANNOTATIONS. Proc IEEE Int Symp Biomed Imaging. 2020 Apr;2020:1910-1914. doi: 10.1109/isbi45749.2020.9098599. Epub 2020 May 22.
Applequist J, Burroughs C, Ramirez A Jr, Merkel PA, Rothenberg ME, Trapnell B, Desnick RJ, Sahin M, Krischer JP. A novel approach to conducting clinical trials in the community setting: utilizing patient-driven platforms and social media to drive web-based patient recruitment. BMC Med Res Methodol. 2020 Mar 13;20(1):58. doi: 10.1186/s12874-020-00926-y.
Afshar Saber W, Sahin M. Recent advances in human stem cell-based modeling of Tuberous Sclerosis Complex. Mol Autism. 2020 Feb 19;11(1):16. doi: 10.1186/s13229-020-0320-2.
Kohlenberg TM, Trelles MP, McLarney B, Betancur C, Thurm A, Kolevzon A. Psychiatric illness and regression in individuals with Phelan-McDermid syndrome. J Neurodev Disord. 2020 Feb 12;12(1):7. doi: 10.1186/s11689-020-9309-6.
Schoenberger A, Capal JK, Ondracek A, Horn PS, Murray D, Byars AW, Pearson DA, Williams ME, Bebin M, Northrup H, Wu JY, Sahin M, Krueger DA. Language predictors of autism spectrum disorder in young children with tuberous sclerosis complex. Epilepsy Behav. 2020 Feb;103(Pt A):106844. doi: 10.1016/j.yebeh.2019.106844. Epub 2019 Dec 18.
Yehia L, Seyfi M, Niestroj LM, Padmanabhan R, Ni Y, Frazier TW, Lal D, Eng C. Copy Number Variation and Clinical Outcomes in Patients With Germline PTEN Mutations. JAMA Netw Open. 2020 Jan 3;3(1):e1920415. doi: 10.1001/jamanetworkopen.2019.20415.
Peters JM, Hyde DE, Chu CJ, Boom M, Scherrer B, Madsen JR, Stone SS, Ouaalam H, Prabhu SP, Sahin M, Warfield SK. Lesion-Constrained Electrical Source Imaging: A Novel Approach in Epilepsy Surgery for Tuberous Sclerosis Complex. J Clin Neurophysiol. 2020 Jan;37(1):79-86. doi: 10.1097/WNP.0000000000000615.
Kolevzon A, Delaby E, Berry-Kravis E, Buxbaum JD, Betancur C. Neuropsychiatric decompensation in adolescents and adults with Phelan-McDermid syndrome: a systematic review of the literature. Mol Autism. 2019 Dec 24;10:50. doi: 10.1186/s13229-019-0291-3. eCollection 2019.
Modi ME, Sahin M. A unified circuit for social behavior. Neurobiol Learn Mem. 2019 Nov;165:106920. doi: 10.1016/j.nlm.2018.08.010. Epub 2018 Aug 24.
Nariai H, Hussain SA, Bernardo D, Fallah A, Murata KK, Nguyen JC, Rajaraman RR, Rao LM, Matsumoto JH, Lerner JT, Salamon N, Elashoff D, Sankar R, Wu JY. Prospective observational study: Fast ripple localization delineates the epileptogenic zone. Clin Neurophysiol. 2019 Nov;130(11):2144-2152. doi: 10.1016/j.clinph.2019.08.026. Epub 2019 Sep 17.
Ahtam B, Dehaes M, Sliva DD, Peters JM, Krueger DA, Bebin EM, Northrup H, Wu JY, Warfield SK, Sahin M, Grant PE; TACERN Study Group. Resting-State fMRI Networks in Children with Tuberous Sclerosis Complex. J Neuroimaging. 2019 Nov;29(6):750-759. doi: 10.1111/jon.12653. Epub 2019 Jul 14.
Busch RM, Srivastava S, Hogue O, Frazier TW, Klaas P, Hardan A, Martinez-Agosto JA, Sahin M, Eng C; Developmental Synaptopathies Consortium. Neurobehavioral phenotype of autism spectrum disorder associated with germline heterozygous mutations in PTEN. Transl Psychiatry. 2019 Oct 8;9(1):253. doi: 10.1038/s41398-019-0588-1.
Yehia L, Ni Y, Feng F, Seyfi M, Sadler T, Frazier TW, Eng C. Distinct Alterations in Tricarboxylic Acid Cycle Metabolites Associate with Cancer and Autism Phenotypes in Cowden Syndrome and Bannayan-Riley-Ruvalcaba Syndrome. Am J Hum Genet. 2019 Oct 3;105(4):813-821. doi: 10.1016/j.ajhg.2019.09.004. Epub 2019 Sep 26.
Witmer C, Mattingly A, DʼSouza P, Thurm A, Hadigan C. Incontinence in Phelan-McDermid Syndrome. J Pediatr Gastroenterol Nutr. 2019 Aug;69(2):e39-e42. doi: 10.1097/MPG.0000000000002342.
Davis PE, Kapur K, Filip-Dhima R, Trowbridge SK, Little E, Wilson A, Leuchter A, Bebin EM, Krueger D, Northrup H, Wu JY, Sahin M, Peters JM; Tuberous Sclerosis Autism Centers of Excellence Research Network. Increased electroencephalography connectivity precedes epileptic spasm onset in infants with tuberous sclerosis complex. Epilepsia. 2019 Aug;60(8):1721-1732. doi: 10.1111/epi.16284. Epub 2019 Jul 12.
Farach LS, Pearson DA, Woodhouse JP, Schraw JM, Sahin M, Krueger DA, Wu JY, Bebin EM, Lupo PJ, Au KS, Northrup H; TACERN Study Group. Tuberous Sclerosis Complex Genotypes and Developmental Phenotype. Pediatr Neurol. 2019 Jul;96:58-63. doi: 10.1016/j.pediatrneurol.2019.03.003. Epub 2019 Mar 13.
Peters JM, Struyven RR, Prohl AK, Vasung L, Stajduhar A, Taquet M, Bushman JJ, Lidov H, Singh JM, Scherrer B, Madsen JR, Prabhu SP, Sahin M, Afacan O, Warfield SK. White matter mean diffusivity correlates with myelination in tuberous sclerosis complex. Ann Clin Transl Neurol. 2019 Jul;6(7):1178-1190. doi: 10.1002/acn3.793. Epub 2019 Jun 23.
Smith IN, Thacker S, Seyfi M, Cheng F, Eng C. Conformational Dynamics and Allosteric Regulation Landscapes of Germline PTEN Mutations Associated with Autism Compared to Those Associated with Cancer. Am J Hum Genet. 2019 May 2;104(5):861-878. doi: 10.1016/j.ajhg.2019.03.009. Epub 2019 Apr 18.
Marami B, Scherrer B, Khan S, Afacan O, Prabhu SP, Sahin M, Warfield SK, Gholipour A. Motion-robust diffusion compartment imaging using simultaneous multi-slice acquisition. Magn Reson Med. 2019 May;81(5):3314-3329. doi: 10.1002/mrm.27613. Epub 2018 Nov 16.
Smith IN, Thacker S, Jaini R, Eng C. Dynamics and structural stability effects of germline PTEN mutations associated with cancer versus autism phenotypes. J Biomol Struct Dyn. 2019 Apr;37(7):1766-1782. doi: 10.1080/07391102.2018.1465854. Epub 2018 May 14.
Yehia L, Ngeow J, Eng C. PTEN-opathies: from biological insights to evidence-based precision medicine. J Clin Invest. 2019 Feb 1;129(2):452-464. doi: 10.1172/JCI121277. Epub 2019 Jan 7.
Peters JM, Prohl A, Kapur K, Nath A, Scherrer B, Clancy S, Prabhu SP, Sahin M, Franz DN, Warfield SK, Krueger DA. Longitudinal Effects of Everolimus on White Matter Diffusion in Tuberous Sclerosis Complex. Pediatr Neurol. 2019 Jan;90:24-30. doi: 10.1016/j.pediatrneurol.2018.10.005. Epub 2018 Oct 18.
Srivastava S, Scherrer B, Prohl AK, Filip-Dhima R, Kapur K, Kolevzon A, Buxbaum JD, Berry-Kravis E, Soorya L, Thurm A, Powell CM, Bernstein JA, Warfield SK, Sahin M; Developmental Synaptopathies Consortium. Volumetric Analysis of the Basal Ganglia and Cerebellar Structures in Patients with Phelan-McDermid Syndrome. Pediatr Neurol. 2019 Jan;90:37-43. doi: 10.1016/j.pediatrneurol.2018.09.008. Epub 2018 Sep 21.
Hussain SA, Schmid E, Peters JM, Goyal M, Bebin EM, Northrup H, Sahin M, Krueger DA, Wu JY; Tuberous Sclerosis Complex Autism Center of Excellence Network. High vigabatrin dosage is associated with lower risk of infantile spasms relapse among children with tuberous sclerosis complex. Epilepsy Res. 2018 Dec;148:1-7. doi: 10.1016/j.eplepsyres.2018.09.016. Epub 2018 Oct 2.
Nariai H, Wu JY, Bernardo D, Fallah A, Sankar R, Hussain SA. Interrater reliability in visual identification of interictal high-frequency oscillations on electrocorticography and scalp EEG. Epilepsia Open. 2018 Nov 2;3(Suppl Suppl 2):127-132. doi: 10.1002/epi4.12266. eCollection 2018 Dec.
Frazier TW, Klingemier EW, Parikh S, Speer L, Strauss MS, Eng C, Hardan AY, Youngstrom EA. Development and Validation of Objective and Quantitative Eye Tracking-Based Measures of Autism Risk and Symptom Levels. J Am Acad Child Adolesc Psychiatry. 2018 Nov;57(11):858-866. doi: 10.1016/j.jaac.2018.06.023. Epub 2018 Sep 13.
Baumer FM, Peters JM, Clancy S, Prohl AK, Prabhu SP, Scherrer B, Jansen FE, Braun KPJ, Sahin M, Stamm A, Warfield SK. Corpus Callosum White Matter Diffusivity Reflects Cumulative Neurological Comorbidity in Tuberous Sclerosis Complex. Cereb Cortex. 2018 Oct 1;28(10):3665-3672. doi: 10.1093/cercor/bhx247.
Modi ME, Sahin M. The Way Forward for Mechanism-Based Therapeutics in Genetically Defined Neurodevelopmental Disorders. Clin Pharmacol Ther. 2018 Oct;104(4):603-606. doi: 10.1002/cpt.1181. Epub 2018 Aug 12.
Jacobs J, Wu JY, Perucca P, Zelmann R, Mader M, Dubeau F, Mathern GW, Schulze-Bonhage A, Gotman J. Removing high-frequency oscillations: A prospective multicenter study on seizure outcome.. Neurology. 2018 Sep 11;91(11):e1040-e1052. doi: 10.1212/WNL.0000000000006158. Epub 2018 Aug 17. PMID: 30120133; PMCID:PMC6140372
de Vries PJ, Wilde L, de Vries MC, Moavero R, Pearson DA, Curatolo P. A clinical update on tuberous sclerosis complex-associated neuropsychiatric disorders (TAND). Am J Med Genet C Semin Med Genet. 2018 Sep;178(3):309-320. doi: 10.1002/ajmg.c.31637. Epub 2018 Aug 16.
Peron A, Au KS, Northrup H. Genetics, genomics, and genotype-phenotype correlations of TSC: Insights for clinical practice. Am J Med Genet C Semin Med Genet. 2018 Sep;178(3):281-290. doi: 10.1002/ajmg.c.31651. Epub 2018 Sep 26.
Peron A, Northrup H. Tuberous sclerosis complex. Am J Med Genet C Semin Med Genet. 2018 Sep;178(3):274-277. doi: 10.1002/ajmg.c.31657. Epub 2018 Oct 16.
Soorya L, Leon J, Trelles MP, Thurm A. Framework for assessing individuals with rare genetic disorders associated with profound intellectual and multiple disabilities (PIMD): the example of Phelan McDermid Syndrome. Clin Neuropsychol. 2018 Aug-Oct;32(7):1226-1255. doi: 10.1080/13854046.2017.1413211. Epub 2017 Dec 21.
van der Poest Clement EA, Sahin M, Peters JM. Vigabatrin for Epileptic Spasms and Tonic Seizures in Tuberous Sclerosis Complex. J Child Neurol. 2018 Jul;33(8):519-524. doi: 10.1177/0883073818768309. Epub 2018 Apr 24.
Bernardo D, Nariai H, Hussain SA, Sankar R, Salamon N, Krueger DA, Sahin M, Northrup H, Bebin EM, Wu JY; UCLA Pediatric Epilepsy Group; TACERN Study Group. Visual and semi-automatic non-invasive detection of interictal fast ripples: A potential biomarker of epilepsy in children with tuberous sclerosis complex. Clin Neurophysiol. 2018 Jul;129(7):1458-1466. doi: 10.1016/j.clinph.2018.03.010. Epub 2018 Apr 3.
Curtin P, Austin C, Curtin A, Gennings C, Arora M; (for the Emergent Dynamical Systems Group), Tammimies K, Willfors C, Berggren S, Siper P, Rai D, Meyering K, Kolevzon A, Mollon J, David AS, Lewis G, Zammit S, Heilbrun L, Palmer RF, Wright RO, Bölte S, Reichenberg A. Dynamical features in fetal and postnatal zinc-copper metabolic cycles predict the emergence of autism spectrum disorder. Sci Adv. 2018 May 30;4(5):eaat1293. doi: 10.1126/sciadv.aat1293. eCollection 2018 May.
De Rubeis S, Siper PM, Durkin A, Weissman J, Muratet F, Halpern D, Trelles MDP, Frank Y, Lozano R, Wang AT, Holder JL Jr, Betancur C, Buxbaum JD, Kolevzon A. Delineation of the genetic and clinical spectrum of Phelan-McDermid syndrome caused by SHANK3 point mutations. Mol Autism. 2018 Apr 27;9:31. doi: 10.1186/s13229-018-0205-9. eCollection 2018.
Srivastava S, Prohl AK, Scherrer B, Kapur K, Krueger DA, Warfield SK, Sahin M; TACERN Study Group. Cerebellar volume as an imaging marker of development in infants with tuberous sclerosis complex. Neurology. 2018 Apr 24;90(17):e1493-e1500. doi: 10.1212/WNL.0000000000005352. Epub 2018 Mar 23.
Rensonnet G, Scherrer B, Warfield SK, Macq B, Taquet M. Assessing the validity of the approximation of diffusion-weighted-MRI signals from crossing fascicles by sums of signals from single fascicles. Magn Reson Med. 2018 Apr;79(4):2332-2345. doi: 10.1002/mrm.26832. Epub 2017 Jul 16.
Khan OI, Zhou X, Leon J, Kessler R, Gaughan T, D'Souza P, Gropman A, Cohen N, Rennert O, Buckley A, Inati S, Thurm A. Prospective longitudinal overnight video-EEG evaluation in Phelan-McDermid Syndrome. Epilepsy Behav. 2018 Mar;80:312-320. doi: 10.1016/j.yebeh.2017.11.034. Epub 2018 Feb 3.
Byrd V, Getz T, Padmanabhan R, Arora H, Eng C. The microbiome in PTEN hamartoma tumor syndrome. Endocr Relat Cancer. 2018 Mar;25(3):233-243. doi: 10.1530/ERC-17-0442. Epub 2017 Dec 12.
Farach LS, Little ME, Duker AL, Logan CV, Jackson A, Hecht JT, Bober M. The expanding phenotype of RNU4ATAC pathogenic variants to Lowry Wood syndrome. Am J Med Genet A. 2018 Feb;176(2):465-469. doi: 10.1002/ajmg.a.38581. Epub 2017 Dec 19.
Siroky BJ, Towbin AJ, Trout AT, Schäfer H, Thamann AR, Agricola KD, Tudor C, Capal J, Dixon BP, Krueger DA, Franz DN.. Improvement in Renal Cystic Disease of Tuberous Sclerosis Complex After Treatment with Mammalian Target of Rapamycin Inhibitor. J Pediatr. 2017 Aug;187:318-322.e2. doi: 10.1016/j.jpeds.2017.05.015. Epub 2017 Jun 7.
Frazier TW, Strauss M, Klingemier EW, Zetzer EE, Hardan AY, Eng C, Youngstrom EA. A Meta-Analysis of Gaze Differences to Social and Nonsocial Information Between Individuals With and Without Autism. J Am Acad Child Adolesc Psychiatry. 2017 Jul;56(7):546-555. doi: 10.1016/j.jaac.2017.05.005. Epub 2017 May 11.
Srivastava S, Sahin M. Autism spectrum disorder and epileptic encephalopathy: common causes, many questions. J Neurodev Disord. 2017 Jun 23;9:23. doi: 10.1186/s11689-017-9202-0. PMID: 28649286; PMCID: PMC5481888.
Martin KR, Zhou W, Bowman MJ, Shih J, Au KS, Dittenhafer-Reed KE, Sisson KA, Koeman J, Weisenberger DJ, Cottingham SL, DeRoos ST, Devinsky O, Winn ME, Cherniack AD, Shen H, Northrup H, Krueger DA, MacKeigan JP. The genomic landscape of tuberous sclerosis complex. Nat Commun. 2017 Jun 15;8:15816. doi: 10.1038/ncomms15816.
Siper PM, Kolevzon A, Wang AT, Buxbaum JD, Tavassoli T. A clinician-administered observation and corresponding caregiver interview capturing DSM-5 sensory reactivity symptoms in children with ASD. Autism Res. 2017 Jun;10(6):1133-1140. doi: 10.1002/aur.1750. Epub 2017 Mar 11.
Rankine J, Li E, Lurie S, Rieger H, Fourie E, Siper PM, Wang AT, Buxbaum JD, Kolevzon A. Language ENvironment Analysis (LENA) in Phelan-McDermid Syndrome: Validity and Suggestions for Use in Minimally Verbal Children with Autism Spectrum Disorder. J Autism Dev Disord. 2017 Jun;47(6):1605-1617. doi: 10.1007/s10803-017-3082-8.
Capal JK, Bernardino-Cuesta B, Horn PS, et al. Influence of seizures on early development in tuberous sclerosis complex. Epilepsy Behav. 2017;70(Pt A):245-252. PMID: 28457992, PMCID: PMC5497719.
Hussain SA, Mathern GW, Hung P, Weng J, Sankar R, Wu JY. Intraoperative fast ripples independently predict postsurgical epilepsy outcome: Comparison with other electrocorticographic phenomena. Epilepsy Res. 2017;135:79-86. PMID: 28644979, PMCID: PMC5568451.
Davis PE, Filip-Dhima R, Sideridis G, Peters JM, Au KS, Northrup H, Bebin EM, Wu JY, Krueger D, Sahin M; Tuberous Sclerosis Complex Autism Center of Excellence Research Network. Presentation and Diagnosis of Tuberous Sclerosis Complex in Infants. Pediatrics. 2017;140(6). PMID: 29101226, PMCID: PMC5703775.
Capal JK, Horn PS, Murray DS, Byars AW, Bing NM, Kent B, Bucher LA, Williams ME, O'Kelley S, Pearson DA, Sahin M, Krueger DA; TACERN Study Group. Utility of the Autism Observation Scale for Infants in Early Identification of Autism in Tuberous Sclerosis Complex. Pediatr Neurol. 2017;75:80-86. PMID: 28844798, PMCID: PMC5610103.
Krueger DA, Wilfong AA, Mays M, Talley CM, Agricola K, Tudor C, Capal J, Holland-Bouley K, Franz DN. Long-term treatment of epilepsy with everolimus in tuberous sclerosis. Neurology. 2016 Dec 6;87(23):2408-2415. doi: 10.1212/WNL.0000000000003400. Epub 2016 Nov 4. PMID: 27815402; PMCID: PMC5177677.
Markowitz LA, Reyes C, Embacher RA, Speer LL, Roizen N, Frazier TW. Development and psychometric evaluation of a psychosocial quality-of-life questionnaire for individuals with autism and related developmental disorders. Autism. 2016 Oct;20(7):832-44. doi: 10.1177/1362361315611382. Epub 2015 Dec 10.
Scherrer B, Schwartzman A, Taquet M, Sahin M, Prabhu SP, Warfield SK. Characterizing brain tissue by assessment of the distribution of anisotropic microstructural environments in diffusion-compartment imaging (DIAMOND). Magn Reson Med. Sep 12 2015. PMID: 26362832.
Sahin M, Henske EP, Manning BD, Ess KC, Bissler JJ, Klann E, Kwiatkowski DJ, Roberds SL, Silva AJ, Hillaire-Clarke CS, Young LR, Zervas M, Mamounas LA; Tuberous Sclerosis Complex Working Group to Update the Research Plan. Advances and Future Directions for Tuberous Sclerosis Complex Research: Recommendations From the 2015 Strategic Planning Conference. Pediatr Neurol. 2016 Jul;60:1-12. doi: 10.1016/j.pediatrneurol.2016.03.015. Epub 2016 Apr 2. PMID: 27267556; PMCID: PMC4921275.
Im K, Ahtam B, Haehn D, Peters JM, Warfield SK, Sahin M, Ellen Grant P. Altered Structural Brain Networks in Tuberous Sclerosis Complex. Cereb Cortex. 2016 May;26(5):2046-58. doi: 10.1093/cercor/bhv026. Epub 2015 Mar 5. PMID: 25750257; PMCID: PMC4830286.
Dölen G, Sahin M. Editorial: Essential Pathways and Circuits of Autism Pathogenesis. Front Neurosci. 2016 Apr 26;10:182. doi: 10.3389/fnins.2016.00182. eCollection 2016.
Frazier TW, Klingemier EW, Beukemann M, Speer L, Markowitz L, Parikh S, Wexberg S, Giuliano K, Schulte E, Delahunty C, Ahuja V, Eng C, Manos MJ, Hardan AY, Youngstrom EA, Strauss MS. Development of an Objective Autism Risk Index Using Remote Eye Tracking. J Am Acad Child Adolesc Psychiatry. Apr 2016;55(4):301-309. PMID: 27015721, PMCID: PMC4808563.
Ebrahimi-Fakhari D, Saffari A, Wahlster L, Lu J, Byrne S, Hoffmann GF, Jungbluth H, Sahin M. Congenital disorders of autophagy: an emerging novel class of inborn errors of neuro-metabolism. Brain. 2016 Feb;139(Pt 2):317-37. doi: 10.1093/brain/awv371. Epub 2015 Dec 29. PMID: 26715604; PMCID: PMC5841365.
Marami B, Scherrer B, Afacan O, Erem B, Warfield SK, Gholipour A. Motion-Robust Diffusion-Weighted Brain MRI Reconstruction Through Slice-Level Registration-Based Motion Tracking. IEEE Trans Med Imaging. 2016;35(10):2258-2269. PMID: 27834639, PMCID: PMC5108524.
Siper PM, Zemon V, Gordon J, et al. Siper PM. PLoS ONE. 2016;11(10):e0164422. PMID: 27716799, PMCID: PMC5055293.
Keppler-Noreuil KM, Parker VE, Darling TN, Martinez-Agosto JA. Somatic overgrowth disorders of the PI3K/AKT/mTOR pathway & therapeutic strategies. Am J Med Genet C Semin Med Genet. 2016;172(4):402-421. PMID: 27860216, PMCID: PMC5592089.
The phosphatidylinositol-3-kinase (PI3K)/AKT/mTOR signaling pathway plays an essential role in regulation of normal cell growth, metabolism, and survival. Somatic activating mutations in the PI3K/AKT/mTOR pathway are among the most common mutations identified in cancer, and have been shown to cause a spectrum of overgrowth syndromes including PIK3CA-Related Overgrowth Spectrum, Proteus syndrome, and brain overgrowth conditions. Clinical findings in these disorders may be isolated or multiple, including sporadic or mosaic overgrowth (adipose, skeletal, muscle, brain, vascular, or lymphatic), and skin abnormalities (including epidermal nevi, hyper-, and hypopigmented lesions), and have the potential risk of tumorigenesis. Key negative regulators of the PI3K-AKT signaling pathway include PTEN and TSC1/TSC2 and germline loss-of function mutations of these genes are established to cause PTEN Hamartoma Tumor Syndrome and Tuberous Sclerosis Complex. Mosaic forms of these conditions lead to increased activation of PI3K and mTOR at affected sites and there is phenotypic overlap between these conditions. All are associated with significant morbidity with limited options for treatment other than symptomatic therapies and surgeries. As dysregulation of the PI3K/AKT/mTOR pathway has been implicated in cancer, several small molecule inhibitors targeting different components of the PI3K/AKT/mTOR signaling pathway are under clinical investigation. The development of these therapies brings closer the prospect of targeting treatment for somatic PI3K/AKT/mTOR-related overgrowth syndromes. This review describes the clinical findings, gene function and pathogenesis of these mosaic overgrowth syndromes, and presents existing and future treatment strategies to reduce or prevent associated complications of these disorders. © 2016 Wiley Periodicals, Inc.
Costales J, Kolevzon A. The therapeutic potential of insulin-like growth factor-1 in central nervous system disorders. Neurosci Biobehav Rev. 2016;63:207-222. PMID: 26780584, PMCID: PMC4790729.
Taquet M, Scherrer B, Boumal N, Peters JM, Macq B, Warfield SK. Improved fidelity of brain microstructure mapping from single-shell diffusion MRI. Med Image Anal. Dec 2015;26(1):268- 286. PMID: 26529580, PMCID: PMC4679640.
Sahin M, Sur M. Genes, circuits, and precision therapies for autism and related neurodevelopmental disorders. Science. Nov 20 2015;350(6263). PMID: 26472761, PMCID: PMC4739545.
He X, Thacker S, Romigh T, Yu Q, Frazier TW Jr, Eng C. Cytoplasm-predominant Pten associates with increased region-specific brain tyrosine hydroxylase and dopamine D2 receptors in mouse model with autistic traits. Mol Autism. 2015 Nov 17;6:63. doi: 10.1186/s13229-015-0056-6. eCollection 2015.
Tyburczy ME, Dies KA, Glass J, Camposano S, Chekaluk Y, Thorner AR, Lin L, Krueger D, Franz DN, Thiele EA, Sahin M, Kwiatkowski DJ. Mosaic and Intronic Mutations in TSC1/TSC2 Explain the Majority of TSC Patients with No Mutation Identified by Conventional Testing. PLoS Genet. 2015 Nov 5;11(11):e1005637. doi: 10.1371/journal.pgen.1005637. eCollection 2015 Nov.
Frazier TW, Youngstrom EA, Hardan AY, Georgiades S, Constantino JN, Eng C. Quantitative autism symptom patterns recapitulate differential mechanisms of genetic transmission in single and multiple incidence families. Mol Autism. 2015 Oct 27;6:58. doi: 10.1186/s13229-015-0050-z. eCollection 2015.
Tilot AK, Frazier TW 2nd, Eng C. Balancing Proliferation and Connectivity in PTEN-associated Autism Spectrum Disorder. Neurotherapeutics. 2015 Jul;12(3):609-19. doi: 10.1007/s13311-015-0356-8. PMID: 25916396; PMCID: PMC4489960.
Neul JL, Sahin M. Therapeutic Advances in Autism and Other Neurodevelopmental Disorders. Neurotherapeutics. Jul 2015;12(3):519-520. PMID: 26076992, PMCID: PMC4489958.
Davis PE, Peters JM, Krueger DA, Sahin M. Tuberous Sclerosis: A New Frontier in Targeted Treatment of Autism. Neurotherapeutics. Jul 2015;12(3):572-583. PMID: 25986747, PMCID: PMC4489948.
Baumer FM, Song JW, Mitchell PD, Pienaar R, Sahin M, Grant PE, Takahashi E. Longitudinal changes in diffusion properties in white matter pathways of children with tuberous sclerosis complex. Pediatr Neurol. Jun 2015;52(6):615-623. PMID: 25817702, PMCID: PMC4442035.
Ebrahimi-Fakhari D, Sahin M. Autism and the synapse: emerging mechanisms and mechanism-based therapies. Curr Opin Neurol. Apr 2015;28(2):91-102. PMID: 25695134.
Sundberg M, Sahin M. Cerebellar Development and Autism Spectrum Disorder in Tuberous Sclerosis Complex. J Child Neurol. Aug 24 2015. PMID: 26303409, PMCID: PMC4644486.
Hussain SA, Kwong G, Millichap JJ, Mytinger JR, Ryan N, Matsumoto JH, Wu JY, Lerner JT, Sankar R. Hypsarrhythmia assessment exhibits poor interrater reliability: a threat to clinical trial validity. Epilepsia. 2015 Jan;56(1):77-81. doi: 10.1111/epi.12861. Epub 2014 Nov 10.
Lipton JO, Sahin M. The neurology of mTOR. Neuron. Oct 22 2014;84(2):275-291. PMID: 25374355, PMCID: PMC4223653.
The mechanistic target of rapamycin (mTOR) signaling pathway is a crucial cellular signaling hub that, like the nervous system itself, integrates internal and external cues to elicit critical outputs including growth control, protein synthesis, gene expression, and metabolic balance. The importance of mTOR signaling to brain function is underscored by the myriad disorders in which mTOR pathway dysfunction is implicated, such as autism, epilepsy, and neurodegenerative disorders. Pharmacological manipulation of mTOR signaling holds therapeutic promise and has entered clinical trials for several disorders. Here, we review the functions of mTOR signaling in the normal and pathological brain, highlighting ongoing efforts to translate our understanding of cellular physiology into direct medical benefit for neurological disorders.
Mohajer A, Sevagamoorthy A, Bean K, Mutua S, Pang F, Adang LA. Characterizing Diagnostic Delays in Metachromatic Leukodystrophy: A Real-World Data Approach. J Inherit Metab Dis. 2025 Jul;48(4):e70049. doi: 10.1002/jimd.70049. PMID: 40457575; PMCID: PMC12130617.
Metachromatic leukodystrophy (MLD) is a rare inherited disorder that causes progressive damage to the nervous system. The subtypes of MLD are defined by the onset of neurodegeneration, but less is known about the earliest features of this inborn error in metabolism.
In this study, researchers found that many children experience subtle early features in the months to years prior to diagnosis. The early medical journeys of children were mapped using two independent payor-system databases. Every medical encounter prior to diagnosis was captured. Across these cohorts, they found that children frequently presented within the medical system with signs and symptoms of disease, including early developmental delay, feeding issues, gallbladder problems, and abnormal eye movements. This work was complemented by similar findings from an MLD natural history study, which is supported through the GLIA-CTN.
Authors note that this study highlights early features of MLD and defines barriers to diagnosis, further supporting the need for early screening. By better understanding the barriers to diagnosis and characterizing how MLD begins, we can better define clinical monitoring guidelines in presymptomatic children and define ideal windows for intervention to improve outcomes. This work underscores the critical need for newborn screening to definitively diagnose children prior to disease onset.
Du S, Zhou Y, Li D, Lier J, Cella M, Tada M, Hamasaki H, Wu J, Cai Z, Orthmann-Murphy JL, Kakita A, Kipnis J, Bergner CG, Colonna M. Mutations in the human CSF1R gene impact microglia’s maintenance of brain white matter integrity. Nat Immunol. 2025 Jul;26(7):1198-1211. doi: 10.1038/s41590-025-02195-7. Epub 2025 Jun 26. PMID: 40571738.
Adult-onset leukoencephalopathy with axonal spheroids and pigmented glia (ALSP) is a neurodegenerative disorder that affects the white matter of the brain. ALSP is caused by mutations in the CSF1R gene, which provides instructions for making a protein called the colony-stimulating factor 1 receptor (CSF1R). This protein plays a crucial role in the growth and survival of immune cells in the brain called microglia.
In this study, researchers examined the molecular mechanisms of ALSP. The team performed single-nucleus RNA sequencing on brain specimens with and without ALSP.
Results revealed distinctive characteristics of ALSP brains, including significantly lower amounts of microglia and impaired maintenance of brain white matter. Authors note that these findings highlight potential therapeutic strategies for ALSP and other genetically caused microgliopathies.
Alves CAPF, Rossi-Espagnet MC, Perez F, Manteghinejad A, Peterson JT, Ganetzky R, Napolitano A, Grassi F, George-Sankoh I, Yildiz H, Muraresku C, Falk MJ, Martinelli D, Longo D, Vanderver A, Gandolfo C, Saneto RP, Goldstein A, Vossough A. Single Large-Scale Mitochondrial Deletion Syndromes: Neuroimaging Phenotypes and Longitudinal Progression in Pediatric Patients. AJNR Am J Neuroradiol. 2025 Jun 3;46(6):1272-1281. doi: 10.3174/ajnr.A8670.
Weiß M, Selig M, Friedrich J, Wierczeiko A, Diederich S, Sigel H, Bredow J, Eichler FS, Nagy A, Seyler D, Holthöfer L, Gerber S, Schweiger S, Linke M, Bley A. Deep Intronic SVA_E Retrotransposition as a Novel Factor in Canavan Disease Pathogenesis. Hum Gene Ther. 2025 Sep;36(17-18):1248-1256. doi: 10.1089/hum.2025.006. Epub 2025 Apr 21. PMID: 40257001.
Canavan disease is a progressive type of leukodystrophy caused by variants in the ASPA gene. In patients with Canavan disease, increased levels of N-acetylaspartic acid lead to symptoms including developmental delay, abnormal muscle tone, and macrocephaly (larger than typical head size). In order for patients to receive a complete diagnosis, all pathogenic variants in the ASPA gene must be identified.
In this study, researchers discovered a new pathogenic variant in Canavan disease. First, the team identified five patients with a clinical and biochemical diagnosis of Canavan disease, but no second pathogenic variant. Next, they used the gene editing tool CRISPR-Cas9 and long-read sequencing technique to analyze the gene structure of ASPA in these patients.
Results revealed a previously unidentified variant of the ASPA gene involving the insertion of an SVA_E retrotransposon into intron 4 of the ASPA gene. Authors note that these findings can improve genetic counseling for families and increase access to gene therapy trials.
Shiva M, Hosseinpour S, Ashrafi MR, Heidari M, Rezaei Z, Zebardast J, Mohammadpour M, Bonkowsky JL, Tavasoli AR. Death Causes Among Iranian Children With Leukodystrophies. J Child Neurol. 2025 Apr;40(4):233-240. doi: 10.1177/08830738241293171. Epub 2024 Nov 18.
Gavazzi F, Charsar B, Hamilton E, Erler JA, Patel V, Woidill S, Sevagamoorthy A, Helman G, Schmidt J, Pizzino A, Muirhead K, Takanohashi A, Bonkowsky JL, Meyerhoffer K, Simons C, Doi H, Satoko M, Matsumoto N, Delgado MR, Sanchez-Castillo M, Wang J, de Carvalho DR, Tournev I, Chamova T, Jordanova A, Clegg NJ, Nicita F, Bertini E, Teng M, Williams D, Tonduti D, Houlden H, Stellingwerff M, Wassmer E, Garcia-Cazorla A, Bernard G, Mirchi A, Toutounchi H, Wolf NI, van der Knaap MS, Shults J, Adang LA, Vanderver AL. The natural history of variable subtypes in pediatric-onset TUBB4A-related leukodystrophy. Mol Genet Metab. 2025 Mar;144(3):109048. doi: 10.1016/j.ymgme.2025.109048. Epub 2025 Feb 1.
Lentini L, Toutounchi H, Chapleau A, Le A, Fournier S, Emari F, Flamini R, Rossi A, Gentile A, Bertini E, Nicita F, Pohl D, Venkateswaran S, Keller S, Rossignol E, Renaud D, Assis Pereira D, Chen X, Vanderver A, Bernard G. Stress and Quality of Life of Parents of Children With POLR3-Related Leukodystrophy: A Cross-Sectional Pilot Study. J Child Neurol. 2025 Jan;40(1):26-38. doi: 10.1177/08830738241283171. Epub 2024 Oct 21.
Mutua S, Sevagamoorthy A, Woidill S, Orchard PJ, Gavazzi F, MacFarland SP, Russo P, Vanderver A, Adang LA. Characterization of gallbladder disease in metachromatic leukodystrophy across the lifespan. Mol Genet Metab. 2025 Jan;144(1):109003. doi: 10.1016/j.ymgme.2024.109003. Epub 2024 Dec 22. PMID: 39733668.
Metachromatic leukodystrophy (MLD) is an inherited lysosomal disorder caused by a missing or abnormal enzyme that cannot break down sulfatides (complex, fat-sugar molecules containing a sulfate group). While the neurological symptoms of MLD are well understood, less is known about how MLD affects other areas of the body. Learning more about how gallbladder complications in MLD affect neurological progression could help identify cases of active disease before neurological symptoms appear.
In this study, researchers characterized gallbladder disease in MLD across the lifespan. The team used natural history study data from 40 individuals with MLD as well as 87 published cases in medical literature to learn more about the disease course—including gallbladder abnormalities—and neurological function.
Results reveal a high prevalence of gallbladder complications in MLD. These complications were commonly found at first evaluation, even in pre- or early symptomatic disease. Authors note that since gallbladder disease can potentially progress to malignancy, regular gallbladder monitoring should be integrated with clinical care, as well as considered a potential predictive biomarker for disease onset.
Nagy A, Eichler F, Bley A, Bredow J, Fay A, Townsend EL, Leiro B, Shaywitz A, Laforet G, Crippen-Harmon D, Williams R. Urine N-Acetylaspartate Distinguishes Phenotypes in Canavan Disease. Hum Gene Ther. 2024 Jan;36(1-2):45-56. doi: 10.1089/hum.2024.168. Epub 2024 Dec 4. PMID: 39628365; PMCID: PMC11807896.
Canavan disease is a progressive, genetic type of leukodystrophy affecting the central nervous system, muscles, and eyes. This disorder is caused by mutations in ASPA—the gene that encodes the enzyme aspartoacylase (ASPA)—leading to accumulation of N-acetylaspartate (NAA), one of the most concentrated metabolites in the brain. While most patients with Canavan disease experience psychomotor deficits within the first 6 months of life and meet few motor milestones, some patients show milder symptoms and meet more milestones.
In this study, researchers explored the relationship between urine NAA levels and disease severity in Canavan disease. The team used data from a natural history study and literature search to compare urine NAA levels and associated genotypes in patients with mild or typical Canavan disease.
Results show that on average, patients with mild disease had lower urine NAA levels than patients with typical disease. Variants R71H and Y288C in the ASPA gene may have higher residual activity in the ASPA enzyme and were unique to patients with mild disease. Authors note that urine NAA levels can distinguish between mild and typical Canavan disease, suggesting the ability to reflect ASPA activity.
Corre CS, Bambery M, Bennett CR, Nagy A, Manley CE, Winter E, Peregoy C, Kelly D, Andonian H, Maciel S, Becker C, Merabet LB, Eichler FS. Characterizing visual processing deficits in cerebral adrenoleukodystrophy. Brain Dev. 2024 Nov;46(10):344-350. doi: 10.1016/j.braindev.2024.09.008. Epub 2024 Oct 12. PMID: 39396893; PMCID: PMC11841130.
Duncan CN, Bledsoe JR, Grzywacz B, Beckman A, Bonner M, Eichler FS, Kühl JS, Harris MH, Slauson S, Colvin RA, Prasad VK, Downey GF, Pierciey FJ, Kinney MA, Foos M, Lodaya A, Floro N, Parsons G, Dietz AC, Gupta AO, Orchard PJ, Thakar HL, Williams DA. Hematologic Cancer after Gene Therapy for Cerebral Adrenoleukodystrophy. N Engl J Med. 2024 Oct 10;391(14):1287-1301. doi: 10.1056/NEJMoa2405541.
Eichler F, Duncan CN, Musolino PL, Lund TC, Gupta AO, De Oliveira S, Thrasher AJ, Aubourg P, Kühl JS, Loes DJ, Amartino H, Smith N, Folloni Fernandes J, Sevin C, Sankar R, Hussain SA, Gissen P, Dalle JH, Platzbecker U, Downey GF, McNeil E, Demopoulos L, Dietz AC, Thakar HL, Orchard PJ, Williams DA. Lentiviral Gene Therapy for Cerebral Adrenoleukodystrophy. N Engl J Med. 2024 Oct 10;391(14):1302-1312. doi: 10.1056/NEJMoa2400442.
Kotes E, Gavazzi F, Woidill S, Sevagamoorthy A, Yang E, Smith V, Dubbs H, Pierce SR, Pucci K, Vithayathil J, Thakur N, Adang LA. Determination of Health Concepts in β-Propeller Protein-Associated Neurodegeneration. J Child Neurol. 2024 Oct 8:8830738241283932. doi: 10.1177/08830738241283932. Epub ahead of print. PMID: 39376195.
β-propeller protein–associated neurodegeneration (BPAN) is a progressive, neurodegenerative disease characterized by buildup of iron in the brain, leading to severe neurologic impairments. Future clinical trials are anticipated to identify new therapies for BPAN.
In this natural history study, researchers characterized family perspectives to define health concepts in BPAN. Among 42 caregivers of children diagnosed with BPAN, the team administered the Vineland Adaptive Behavior Scales, Third Edition—a tool which supports diagnosis of intellectual and developmental disabilities—along with health-related quality of life questionnaires.
Results highlight the effects of BPAN on both patient and caregiver quality of life. Key health concepts identified by families included overall health, comfort, and communication. Authors note that these health concepts will help inform future clinical outcome assessments.
Hofer MJ, Modesti N, Coufal NG, Wang Q, Sase S, Miner JJ, Vanderver A, Bennett ML. The prototypical interferonopathy: Aicardi-Goutières syndrome from bedside to bench. Immunol Rev. 2024 Oct;327(1):83-99. doi: 10.1111/imr.13413. Epub 2024 Oct 29.
Chen Y, Dawes R, Kim HC, Ljungdahl A, Stenton SL, Walker S, Lord J, Lemire G, Martin-Geary AC, Ganesh VS, Ma J, Ellingford JM, Delage E, D'Souza EN, Dong S, Adams DR, Allan K, Bakshi M, Baldwin EE, Berger SI, Bernstein JA, Bhatnagar I, Blair E, Brown NJ, Burrage LC, Chapman K, Coman DJ, Compton AG, Cunningham CA, D'Souza P, Danecek P, Délot EC, Dias KR, Elias ER, Elmslie F, Evans CA, Ewans L, Ezell K, Fraser JL, Gallacher L, Genetti CA, Goriely A, Grant CL, Haack T, Higgs JE, Hinch AG, Hurles ME, Kuechler A, Lachlan KL, Lalani SR, Lecoquierre F, Leitão E, Fevre AL, Leventer RJ, Liebelt JE, Lindsay S, Lockhart PJ, Ma AS, Macnamara EF, Mansour S, Maurer TM, Mendez HR, Metcalfe K, Montgomery SB, Moosajee M, Nassogne MC, Neumann S, O'Donoghue M, O'Leary M, Palmer EE, Pattani N, Phillips J, Pitsava G, Pysar R, Rehm HL, Reuter CM, Revencu N, Riess A, Rius R, Rodan L, Roscioli T, Rosenfeld JA, Sachdev R, Shaw-Smith CJ, Simons C, Sisodiya SM, Snell P, St Clair L, Stark Z, Stewart HS, Tan TY, Tan NB, Temple SEL, Thorburn DR, Tifft CJ, Uebergang E, VanNoy GE, Vasudevan P, Vilain E, Viskochil DH, et al. De novo variants in the RNU4-2 snRNA cause a frequent neurodevelopmental syndrome. Nature. 2024 Aug;632(8026):832-840. doi: 10.1038/s41586-024-07773-7. Epub 2024 Jul 11.
Ferreira da Silva J, Tou CJ, King EM, Eller ML, Rufino-Ramos D, Ma L, Cromwell CR, Metovic J, Benning FMC, Chao LH, Eichler FS, Kleinstiver BP. Click editing enables programmable genome writing using DNA polymerases and HUH endonucleases. Nat Biotechnol. 2024 Jul 22. doi: 10.1038/s41587-024-02324-x. Online ahead of print.
Nomakuchi TT, Teferedegn EY, Li D, Muirhead KJ, Dubbs H, Leonard J, Muraresku C, Sergio E, Arnold K, Pizzino A, Skraban CM, Zackai EH, Wang K, Ganetzky RD, Vanderver AL, Ahrens-Nicklas RC, Bhoj EJK. Utility of genome sequencing in exome-negative pediatric patients with neurodevelopmental phenotypes. Am J Med Genet A. 2024 Jul 19:e63817. doi: 10.1002/ajmg.a.63817. Epub ahead of print. PMID: 39031459.
Neurodevelopmental disorders have a wide range of causes, which can lead to diagnostic challenges. Patients are often subjected to a long course of tests with frequently inconclusive results. Exome sequencing is a comprehensive genetic test that can help evaluate undiagnosed neurodevelopmental disorders. However, these tests may miss rare diagnoses due to technical limitations. While genome sequencing addresses many of these limitations, it is less commonly used due to higher cost and more intense analysis.
In this study, researchers illustrate the diagnostic utility of genome sequencing in pediatric cases of neurodevelopmental disorders following non-diagnostic exome sequencing. The team describes nine cases of individuals presenting with global developmental delay or regression who were diagnosed with genome sequencing after inconclusive exome sequencing tests.
Results show that in these cases, exome sequencing was limited by poor sensitivity for structural variants and non-coding variants, as well as biased coverage of coding regions. Authors note that these findings suggest that individuals presenting with neurodevelopmental disability could benefit from genome sequencing, either as a follow-up or in place of non-diagnostic exome sequencing.
Thorpe E, Williams T, Shaw C, Chekalin E, Ortega J, Robinson K, Button J, Jones MC, Campo MD, Basel D, McCarrier J, Keppen LD, Royer E, Foster-Bonds R, Duenas-Roque MM, Urraca N, Bosfield K, Brown CW, Lydigsen H, Mroczkowski HJ, Ward J, Sirchia F, Giorgio E, Vaux K, Salguero HP, Lumaka A, Mubungu G, Makay P, Ngole M, Lukusa PT, Vanderver A, Muirhead K, Sherbini O, Lah MD, Anderson K, Bazalar-Montoya J, Rodriguez RS, Cornejo-Olivas M, Milla-Neyra K, Shinawi M, Magoulas P, Henry D, Gibson K, Wiafe S, Jayakar P, Salyakina D, Masser-Frye D, Serize A, Perez JE, Taylor A, Shenbagam S, Abou Tayoun A, Malhotra A, Bennett M, Rajan V, Avecilla J, Warren A, Arseneault M, Kalista T, Crawford A, Ajay SS, Perry DL, Belmont J, Taft RJ. The impact of clinical genome sequencing in a global population with suspected rare genetic disease. Am J Hum Genet. 2024 Jul 11;111(7):1271-1281. doi: 10.1016/j.ajhg.2024.05.006. Epub 2024 Jun 5.
Gavazzi F, Vaia Y, Woidill S, Formanowski B, Peixoto de Barcelos I, Sevagamoorthy A, Modesti NB, Charlton L, Cusack SV, Vincent A, D'Aiello R, Jawad A, Galli J, Varesio C, Fazzi E, Orcesi S, Glanzman AM, Lorch S, DeMauro SB, Guez-Barber D, Waldman AT, Vanderver A, Adang LA. Nonverbal Cognitive Skills in Children With Aicardi Goutières Syndrome. Neurology. 2024 Jul 9;103(1):e209541. doi: 10.1212/WNL.0000000000209541. Epub 2024 Jun 10.
Kissell J, Rochmann C, Minini P, Eichler F, Stephen CD, Lau H, Toro C, Johnston JM, Krupnick R, Hamed A, Cox GF. Clinical outcome assessments of disease burden and progression in late-onset GM2 gangliosidoses. Mol Genet Metab. 2024 Jul;142(3):108512. doi: 10.1016/j.ymgme.2024.108512. Epub 2024 Jun 6.
Adang LA, Bonkowsky JL, Boelens JJ, Mallack E, Ahrens-Nicklas R, Bernat JA, Bley A, Burton B, Darling A, Eichler F, Eklund E, Emrick L, Escolar M, Fatemi A, Fraser JL, Gaviglio A, Keller S, Patterson MC, Orchard P, Orthmann-Murphy J, Santoro JD, Schöls L, Sevin C, Srivastava IN, Rajan D, Rubin JP, Van Haren K, Wasserstein M, Zerem A, Fumagalli F, Laugwitz L, Vanderver A. Consensus guidelines for the monitoring and management of metachromatic leukodystrophy in the United States. Cytotherapy. 2024 Jul;26(7):739-748. doi: 10.1016/j.jcyt.2024.03.487. Epub 2024 Apr 1.
Adang LA, Groeschel S, Grzyb C, D'Aiello R, Gavazzi F, Sherbini O, Bronner N, Patel A, Vincent A, Sevagamoorthy A, Mutua S, Muirhead K, Schmidt J, Pizzino A, Yu E, Jin D, Eichler F, Fraser JL, Emrick L, Van Haren K, Boulanger JM, Ruzhnikov M, Sylvain M, Nguyen CÉ, Potic A, Keller S, Fatemi A, Uebergang E, Poe M, Yazdani PA, Bernat J, Lindstrom K, Bonkowsky JL, Bernard G, Stutterd CA, Orchard P, Gupta AO, Ljungberg M, Groenborg S, Zambon A, Locatelli S, Fumagalli F, Elguen S, Kehrer C, Krägeloh-Mann I, Shults J, Vanderver A, Escolar ML. Developmental delay can precede neurologic regression in early onset metachromatic leukodystrophy. Mol Genet Metab. 2024 Aug;142(4):108521. doi: 10.1016/j.ymgme.2024.108521. Epub 2024 Jun 29. PMID: 38964050; PMCID: PMC11348664.
Metachromatic leukodystrophy (MLD) is an inherited lysosomal disorder caused by a missing or abnormal enzyme that cannot break down sulfatides (complex, fat-sugar molecules containing a sulfate group). Since therapies are most effective before patients begin experiencing symptoms, there is a critical need to define this window early in the disease course.
In this study, researchers explored the relationship between early development delay and neurologic regression in late-infantile MLD. The team studied medical records of 351 patients, including the specific ages of gain and loss of developmental milestones.
Results show that early developmental delay precedes regression in a subset of children affected by late-infantile MLD, defining an earlier onset of neurologic dysfunction than previously understood. As real-world data prior to diagnosis revealed early differences from typical development, authors note that close monitoring for early development delay in presymptomatic individuals may help with earlier diagnosis, leading to improved treatment decisions.
Adang LA, D'Aiello R, Takanohashi A, Woidill S, Gavazzi F, Behrens EM, Sullivan KE, Goldbach-Mansky R, de Jesus AA; AGS Clinical Trial Readiness Workgroup; Vanderver A, Shults J. IFN-signaling gene expression as a diagnostic biomarker for monogenic interferonopathies. JCI Insight. 2024 Jun 17;9(14):e178456. doi: 10.1172/jci.insight.178456.
Armangue T, Whitehead MT, Tonduti D, Farina L, Tavasoli AR, Vossough A, Bennett ML, Vaia Y, Bernard G, Salsano E, Mercimek-Andrews S, Waldman A, Vanderver A. Brainstem Chipmunk Sign: A Diagnostic Imaging Clue across All Subtypes of Alexander Disease. AJNR Am J Neuroradiol. 2024 Jun 7;45(6):769-772. doi: 10.3174/ajnr.A8220.
Posern C, Dreyer B, Maier SL, Eichler F, Gelb MH, Santer R, Bley A, Murko S. Quantification of N-acetyl-l-aspartate in dried blood spots: A simple and fast LC-MS/MS neonatal screening method for the diagnosis of Canavan disease. Mol Genet Metab. 2024 Jun;142(2):108489. doi: 10.1016/j.ymgme.2024.108489. Epub 2024 May 3.
Berger JA, Simpao AF, Dubow SR, McClung HA, Liu GW, Waldman AT, Drum ET. A retrospective observational cohort study of the anesthetic management and outcomes of pediatric patients with Alexander disease undergoing lumbar puncture or magnetic resonance imaging. Paediatr Anaesth. 2024 Aug;34(8):810-817. doi: 10.1111/pan.14937. Epub 2024 May 31. PMID: 38818870; PMCID: PMC11223980.
Alexander disease is a rare disorder of the nervous system characterized by leukodystrophy, or the destruction of myelin (the fatty coating surrounding nerve fibers). Patients with Alexander disease can experience developmental delay, seizures, difficulty swallowing, vomiting, and sleep apnea. These symptoms can also lead to complications under general anesthesia. However, not much is known about outcomes related to anesthesia for patients with Alexander disease.
In this study, researchers describe anesthetic outcomes of pediatric patients with Alexander disease undergoing magnetic resonance imaging or lumbar puncture. Among 40 patients undergoing 64 procedures, the team reviewed data on patient characteristics, anesthetic techniques, medications, and complications under anesthesia as well as in the following 24 hours.
Results show that participants did not experience significant complications while undergoing general anesthesia or monitored anesthesia care, demonstrating that patients with Alexander disease can safely be anesthetized for low-risk procedures. Authors note that further study is needed to understand the long-term safety outcomes of repeat anesthetic exposures in patients with Alexander disease.
Yska HAF, Turk BR, Fatemi A, Goodman J, Voermans M, Amos D, Amanat M, van de Stadt S, Engelen M, Smith-Fine A, Keller J. International validation of meaningfulness of postural sway and gait to assess myeloneuropathy in adults with adrenoleukodystrophy. J Inherit Metab Dis. 2024 May 25. doi: 10.1002/jimd.12753. Epub ahead of print. PMID: 38795020.
Adrenoleukodystrophy (ALD) is an X-linked disorder (on the X chromosome) characterized by the disruption in fat metabolism (break down) which leads to the accumulation of long-chain fatty acids throughout the nervous system, adrenal glands, and testes. Individuals with ALD experience a slowly progressive myeloneuropathy, which causes problems with balance and gait. Evaluating this progression can often be complicated due to the inconsistency of symptom patterns. However, wearable sensors could make it easier to collect more frequent information about balance and gait.
_x000D_ _x000D_In this study, researchers assessed balance and gait in adults with ALD using wearable sensors. The team measured postural body sway and gait in 120 participants using a type of wearable device called an accelerometer. Researchers also measured disease severity, as well as falling frequency and quality of life in men.
_x000D_ _x000D_Results show clinically meaningful relationships for sway and gait with use of an assistive device, falling frequency, and quality of life. Authors note that wearable accelerometers are a valid means to measure sway and gait in ALD, which could help improve clinical trial designs to assess myeloneuropathy and monitor disease progression.
Adang LA, Sevagamoorthy A, Sherbini O, Fraser JL, Bonkowsky JL, Gavazzi F, D'Aiello R, Modesti NB, Yu E, Mutua S, Kotes E, Shults J, Vincent A, Emrick LT, Keller S, Van Haren KP, Woidill S, Barcelos I, Pizzino A, Schmidt JL, Eichler F, Fatemi A, Vanderver A. Longitudinal natural history studies based on real-world data in rare diseases: Opportunity and a novel approach. Mol Genet Metab. 2024 May;142(1):108453. doi: 10.1016/j.ymgme.2024.108453. Epub 2024 Mar 18. PMID: 38522179.
In rare diseases, natural history studies are essential to understanding disease progression over time. Prospective studies are limited by fewer available patients at a given time, impacting the timely collection of natural history data. These studies are also unlikely to capture pre-diagnostic clinical trajectories in conditions where diagnostic delays are common.
_x000D_ _x000D_In this study, researchers shared a new approach to creating real-world data-based longitudinal natural history studies for rare diseases. The team outlined various strategies developed by the Global Leukodystrophy Initiative Clinical Trials Network. Strategies include use of standard operating procedures and rigorous processes for staff training, data extraction, source documentation, and data management.
_x000D_ _x000D_Authors note that these strategies will complement prospective studies by enabling the use of existing medical records to collect natural history data on large numbers of patients in a short time and map complete disease trajectory, including the time period before diagnosis.
de Barcelos IP, Woidill S, Gavazzi F, Modesti NB, Sevagamoorthy A, Vanderver A, Adang L. Systematic analysis of genotype-phenotype variability in siblings with Aicardi Goutières Syndrome (AGS). Mol Genet Metab. 2024 May;142(1):108346. doi: 10.1016/j.ymgme.2024.108346. Epub 2024 Feb 13.
Kiefer M, Simione M, Eichler FS, Townsend EL4. Development of an Infantile GM2 Clinical Rating Scale: Remote Assessment of Clinically Meaningful Health-Related Function. J Child Neurol. 2024 May;39(5-6):161-170. doi: 10.1177/08830738241246703. Epub 2024 Apr 25.
Fortin O, Christoffel K, Shoaib A, Venkatesan C, Cilli K, Schroeder JW, Alves C, Ganetzky RD, Fraser JL. Characteristic Fetal Brain MRI Abnormalities in Pyruvate Dehydrogenase Complex Deficiency. medRxiv. 2024 Apr 10:2024.04.08.24303574. doi: 10.1101/2024.04.08.24303574.
Chen Y, Dawes R, Kim HC, Stenton SL, Walker S, Ljungdahl A, Lord J, Ganesh VS, Ma J, Martin-Geary AC, Lemire G, D'Souza EN, Dong S, Ellingford JM, Adams DR, Allan K, Bakshi M, Baldwin EE, Berger SI, Bernstein JA, Brown NJ, Burrage LC, Chapman K, Compton AG, Cunningham CA, D'Souza P, Délot EC, Dias KR, Elias ER, Evans CA, Ewans L, Ezell K, Fraser JL, Gallacher L, Genetti CA, Grant CL, Haack T, Kuechler A, Lalani SR, Leitão E, Fevre AL, Leventer RJ, Liebelt JE, Lockhart PJ, Ma AS, Macnamara EF, Maurer TM, Mendez HR, Montgomery SB, Nassogne MC, Neumann S, O'Leary M, Palmer EE, Phillips J, Pitsava G, Pysar R, Rehm HL, Reuter CM, Revencu N, Riess A, Rius R, Rodan L, Roscioli T, Rosenfeld JA, Sachdev R, Simons C, Sisodiya SM, Snell P, Clair L, Stark Z, Tan TY, Tan NB, Temple SE, Thorburn DR, Tifft CJ, Uebergang E, VanNoy GE, Vilain E, Viskochil DH, Wedd L, Wheeler MT, White SM, Wojcik M, Wolfe LA, Wolfenson Z, Xiao C, Zocche D, Rubenstein JL, Markenscoff-Papadimitriou E, Fica SM, Baralle D, Depienne C, MacArthur DG, Howson JM, Sanders SJ, O'Donnell-Luria A, Whiffin N. De novo variants in the non-coding spliceosomal snRNA gene RNU4-2 are a frequent cause of syndromic neurodevelopmental disorders. medRxiv. 2024 Apr 9:2024.04.07.24305438. doi: 10.1101/2024.04.07.24305438.
Gold JI, Stefanatos AK, Fraser JL, Vanderver A, Cuddapah S. Enasidenib-induced hepatitis in an individual with Type II D2-hydroxyglutaric aciduria. JIMD Rep. 2024 Apr 16;65(3):156-162. doi: 10.1002/jmd2.12421. eCollection 2024 May.
Ashton NJ, Di Molfetta G, Tan K, Blennow K, Zetterberg H, Messing A. Plasma concentrations of glial fibrillary acidic protein, neurofilament light, and tau in Alexander disease. Neurol Sci. 2024 Apr 1. doi: 10.1007/s10072-024-07495-8. Epub ahead of print. PMID: 38558318.
Alexander disease is a rare disorder of the nervous system characterized by leukodystrophy, or the destruction of myelin (the fatty coating surrounding nerve fibers). Biomarkers are needed to help researchers monitor the progression of the disease and response to treatments. Elevated levels of the GFAP protein in the blood of patients with Alexander disease could serve as a possible biomarker. However, therapies currently in development involve targeting GFAP for treatment, highlighting a critical need for additional biomarkers.
_x000D_ _x000D_In this study, researchers explored the potential of biomarkers used in other neurodegenerative diseases for Alexander disease. The team measured concentrations of GFAP, neurofilament light, and tau in blood samples from individuals with Alexander disease and healthy controls.
_x000D_ _x000D_Results show significant changes in these levels in individuals with Alexander disease, especially those with infantile onset.
Cusack SV, Gavazzi F, de Barcelos IP, Modesti NB, Woidill S, Formanowski B, DeMauro SB, Lorch S, Vincent A, Jawad AF, Estilow T, Glanzman AM, Vanderver A, Adang LA. Characterization of Fine Motor and Visual Motor Skills in Aicardi-Goutières Syndrome. J Child Neurol. 2024 Mar;39(3-4):147-154. doi: 10.1177/08830738241241786. Epub 2024 Mar 27.
Gavazzi F, Gonzalez CD, Arnold K, Swantkowski M, Charlton L, Modesti N, Dar AA, Vanderver A, Bennett M, Adang LA. Nucleotide metabolism, leukodystrophies, and CNS pathology. J Inherit Metab Dis. 2024 Feb 29:10.1002/jimd.12721. doi: 10.1002/jimd.12721. Online ahead of print.
Nagy A, Molay F, Hargadon S, Brito Pires C, Grant N, De La Rosa Abreu L, Chen JY, D'Souza P, Macnamara E, Tifft C, Becker C, Melo De Gusmao C, Khurana V, Neumeyer AM, Eichler FS. The spectrum of neurological presentation in individuals affected by TBL1XR1 gene defects. Orphanet J Rare Dis. 2024 Feb 20;19(1):79. doi: 10.1186/s13023-024-03083-3. PMID: 38378692; PMCID: PMC10880200.
TBL1XR1-related disorder is a group of neurodevelopmental disorders caused by variants in the TBL1XR1 gene. As these disorders are rare with a wide range of characteristics, not much is known about the developmental trajectory and progression of neurological symptoms over time.
_x000D_ _x000D_In this study, researchers describe the largest group of patients to date with TBL1XR1-related disorder. The team surveyed caregivers of 41 patients with TBL1XR1-related disorder, focusing on the pregnancy and perinatal course, caregiver-reported developmental trajectory, associated symptoms and diagnoses, neurological progression over time, and genetic information.
_x000D_ _x000D_Results reflect the spectrum of diverse traits in TBL1XR1-related disorder, including developmental delay and regression ranging in severity. Seizures were common, which could be related to language regression. Authors note that further study is needed to determine whether functional differences caused by different variants in the TBL1XR1 gene explain the range of characteristics in this disorder.
Ahmed F, Do N, Vanderver AL, Treat JR. Dyschromatosis symmetrica hereditaria: A clue to early diagnosis of Aicardi-Goutières syndrome. Pediatr Dermatol. 2024 Jan-Feb;41(1):156-157. doi: 10.1111/pde.15437. Epub 2023 Sep 28.
Goldberg G, Coelho L, Mo G, Adang LA, Patne M, Chen Z, Garcia-Bassets I, Mesci P, Muotri AR. TREX1 is required for microglial cholesterol homeostasis and oligodendrocyte terminal differentiation in human neural assembloids. Mol Psychiatry. 2023 Dec 21. doi: 10.1038/s41380-023-02348-w. Online ahead of print.
Gong Y, Laheji F, Berenson A, Li Y, Moser A, Qian A, Frosch M, Sadjadi R, Hahn R, Maguire CA, Eichler F. Role of Basal Forebrain Neurons in Adrenomyeloneuropathy in Mice and Humans. Ann Neurol. 2023 Dec 7. doi: 10.1002/ana.26849. Online ahead of print.
Joung J, Gallison K, Sollee JJ, Vigilante N, Cooper H, Liu GW, Ballester L, Faig W, Waldman AT. Acquisition and Loss of Developmental Milestones and Time to Disease-Related Outcomes in Cerebral Alexander Disease. J Child Neurol. 2023 Dec;38(13-14):672-678. doi: 10.1177/08830738231210040. Epub 2023 Nov 3.
Adang LA, Mowafy S, Herbst ZM, Zhou Z, Schlotawa L, Radhakrishnan K, Bentley B, Pham V, Yu E, Pillai NR, Orchard PJ, De Castro M, Vanderver A, Pasquali M, Gelb MH, Ahrens-Nicklas RC. Biochemical signatures of disease severity in multiple sulfatase deficiency. J Inherit Metab Dis. 2023 Oct 23. doi: 10.1002/jimd.12688. Online ahead of print.
Ramirez Alcantara J, Grant NR, Sethuram S, Nagy A, Becker C, Sahai I, Stanley T, Halper A, Eichler FS. Early Detection of Adrenal Insufficiency: The Impact of Newborn Screening for Adrenoleukodystrophy. J Clin Endocrinol Metab. 2023 Oct 18;108(11):e1306-e1315.
Adrenoleukodystrophy (ALD) is an X-linked disorder (on the X chromosome) characterized by accumulation of very long-chain fatty acids throughout the nervous system, adrenal glands, and testes. Males with ALD have a high risk of developing adrenal insufficiency, which can be life-threatening when undetected. Although newborn screening for ALD is becoming more common, its impact on clinical management has not yet been reported.
In this study, researchers investigated the impact of newborn screening on time to diagnosis of adrenal insufficiency in children with ALD. The team conducted a medical chart review of 116 patients with ALD, extracting information about diagnosis in all patients and adrenal insufficiency surveillance, diagnosis, and treatment in boys with ALD.
Results suggest that implementing newborn screening for ALD leads to significantly earlier detection of adrenal insufficiency, as well as earlier initiation of glucocorticoid supplementation in boys affected by ALD.
Weinhofer I, Rommer P, Gleiss A, Ponleitner M, Zierfuss B, Waidhofer-Söllner P, Fourcade S, Grabmeier-Pfistershammer K, Reinert MC, Göpfert J, Heine A, Yska HAF, Casasnovas C, Cantarín V, Bergner CG, Mallack E, Forss-Petter S, Aubourg P, Bley A, Engelen M, Eichler F, Lund TC, Pujol A, Köhler W, Kühl JS, Berger J. Biomarker-based risk prediction for the onset of neuroinflammation in X-linked adrenoleukodystrophy. EBioMedicine. 2023 Oct;96:104781. doi: 10.1016/j.ebiom.2023.104781. Epub 2023 Sep 7.
Mirchi A, Guay SP, Tran LT, Wolf NI, Vanderver A, Brais B, Sylvain M, Pohl D, Rossignol E, Saito M, Moutton S, González-Gutiérrez-Solana L, Thiffault I, Kruer MC, Moron DG, Kauffman M, Goizet C, Sztriha L, Glamuzina E, Melançon SB, Naidu S, Retrouvey JM, Lacombe S, Bernardino-Cuesta B, De Bie I, Bernard G. Craniofacial features of POLR3-related leukodystrophy caused by biallelic variants in POLR3A, POLR3B and POLR1C. J Med Genet. 2023 Oct;60(10):1026-1034. doi: 10.1136/jmg-2023-109223. Epub 2023 May 16. PMID: 37197783
RNA polymerase III-related or 4H leukodystrophy (POLR3-HLD) is a rare genetic disorder characterized by hypomyelination (inability to produce sufficient myelin, the fatty coating surrounding nerve fibers, at normal levels during development), neurological dysfunction, hypodontia (missing teeth), and hypogonadotropic hypogonadism (delayed puberty). Description of craniofacial features in individuals with POLR3-HLD is currently very limited.
In this study, researchers assessed the craniofacial features of 31 patients with POLR3-HLD. The team also proposed genotype-phenotype correlations based on patients’ facial features.
Results demonstrate that craniofacial abnormalities are common in patients with POLR3-HLD. Authors note that these findings will assist clinicians in diagnosing POLR3-HLD, help to provide care directed to this patient population’s specific needs, and allow future studies characterizing the underlying pathophysiology.
Wong KN, Botto LD, He M, Baker PR 2nd, Vanderver AL, Bonkowsky JL. Novel SLC13A3 Variants and Cases of Acute Reversible Leukoencephalopathy and α-Ketoglutarate Accumulation and Literature Review. Neurol Genet. 2023 Sep 26;9(6):e200101. doi: 10.1212/NXG.0000000000200101. eCollection 2023 Dec.
Schoenmakers DH, Leferink PS, Vanderver A, Bonkowsky JL, Krägeloh-Mann I, Bernard G, Bertini E, Fatemi A, Fogel BL, Wolf NI, Skwirut D, Buck A, Holberg B, Saunier-Vivar EF, Rauner R, Dekker H, van Bokhoven P, Stellingwerff MD, Berkhof J, van der Knaap MS. Core protocol development for phase 2/3 clinical trials in the leukodystrophy vanishing white matter: a consensus statement by the VWM consortium and patient advocates. BMC Neurol. 2023 Aug 17;23(1):305. doi: 10.1186/s12883-023-03354-9.
Gavazzi F, Patel V, Charsar B, Glanzman A, Erler J, Sevagamoorthy A, McKenzie E, Kornafel T, Ballance E, Pierce SR, Teng M, Formanowski B, Woidill S, Shults J, Wassmer E, Tonduti D, Magrinelli F, Bernard G, Van Der Knaap M, Wolf N, Adang L, Vanderver A. Gross Motor Function in Pediatric Onset TUBB4A-Related Leukodystrophy: GMFM-88 Performance and Validation of GMFC-MLD in TUBB4A. J Child Neurol. 2023 Aug;38(8-9):498-504. doi: 10.1177/08830738231188159. Epub 2023 Jul 17.
Gavazzi F, Glanzman AM, Woidill S, Formanowski B, Dixit A, Isaacs D, Kornafel T, Ballance E, Pierce SR, Modesti N, Barcelos I, Cusack SV, Jan AK, Flores Z, Sherbini O, Vincent A, D'Aiello R, Lorch SA, DeMauro SB, Jawad A, Vanderver A, Adang L. Exploration of Gross Motor Function in Aicardi-Goutières Syndrome. J Child Neurol. 2023 Jul 27:8830738231188753. doi: 10.1177/08830738231188753. Epub ahead of print. PMID: 37499181
Aicardi-Goutières syndrome (AGS) is a rare genetic disorder characterized by a spectrum of motor abilities. The AGS Severity Scale is used to measure outcomes in individuals with AGS. However, because of the relatively limited granularity of this tool, there is a need to define tools that can measure function across the AGS spectrum.
In this study, researchers explored gross motor function as an outcome measure of AGS. The team administered the Gross Motor Function Measure–88 (GMFM-88) and AGS Severity Scale in 71 individuals affected by AGS, characterizing performance variability by genotype.
Results support the GMFM-88 as a potential clinical outcome assessment in subsets of the AGS population. Authors note the need for additional validation of outcome measures that can reflect the diverse gross motor function observed in individuals with AGS, including low motor function.
Al-Saady M, Beerepoot S, Plug BC, Breur M, Galabova H, Pouwels PJW, Boelens JJ, Lindemans C, van Hasselt PM, Matzner U, Vanderver A, Bugiani M, van der Knaap MS, Wolf NI. Neurodegenerative disease after hematopoietic stem cell transplantation in metachromatic leukodystrophy. Ann Clin Transl Neurol. 2023 Jul;10(7):1146-1159. doi: 10.1002/acn3.51796. Epub 2023 May 22.
Köhler W, Engelen M, Eichler F, Lachmann R, Fatemi A, Sampson J, Salsano E, Gamez J, Molnar MJ, Pascual S, Rovira M, Vilà A, Pina G, Martín-Ugarte I, Mantilla A, Pizcueta P, Rodríguez-Pascau L, Traver E, Vilalta A, Pascual M, Martinell M, Meya U, Mochel F; ADVANCE Study Group. Safety and efficacy of leriglitazone for preventing disease progression in men with adrenomyeloneuropathy (ADVANCE): a randomised, double-blind, multi-centre, placebo-controlled phase 2-3 trial. Lancet Neurol. 2023 Feb;22(2):127-136. doi: 10.1016/S1474-4422(22)00495-1.
Srivastava S, Shaked HM, Gable K, Gupta SD, Pan X, Somashekarappa N, Han G, Mohassel P, Gotkine M, Doney E, Goldenberg P, Tan QKG, Gong Y, Kleinstiver B, Wishart B, Cope H, Pires CB, Stutzman H, Spillmann RC; Undiagnosed Disease Network; Sadjadi R, Elpeleg O, Lee CH, Bellen HJ, Edvardson S, Eichler F, Dunn TM. SPTSSA variants alter sphingolipid synthesis and cause a complex hereditary spastic paraplegia. Brain. 2023 Jan 30:awac460. doi: 10.1093/brain/awac460. Epub ahead of print. PMID: 36718090.
Hereditary spastic paraplegia (HSP) is a group of neurodegenerative disorders that primarily affect the upper motor neurons. In the nervous system, a diverse family of lipids called sphingolipids play a critical role in structural and signaling functions. The synthesis of sphingolipids is regulated by the protein SPTSSA.
In this study, researchers identified three children with a complex form of HSP. The team used exome sequencing to discover two different disease-causing variants in the SPTSSA gene. Next, they investigated the effects of these variants on sphingolipid synthesis.
Findings showed that the variants in SPTSSA caused excessive sphingolipid synthesis, leading to HSP. Authors note that these findings provide a better understanding of the elevated sphingolipid synthesis involved in progressive neurodegenerative diseases.
Modesti NB, Evans SH, Jaffe N, Vanderver A, Gavazzi F. Early recognition of patients with leukodystrophies. Curr Probl Pediatr Adolesc Health Care. 2022 Dec;52(12):101311. doi: 10.1016/j.cppeds.2022.101311. Epub 2022 Dec 2.
Perez G, Young L, Kravitz R, Sheehan D, Adang L, Van Haren K, Lin JL, Jaffe NN, Kuo D, Ball L, Keller J, Sank J, DiVito D, Naime S. Pulmonological issues. Curr Probl Pediatr Adolesc Health Care. 2022 Dec;52(12):101313. doi: 10.1016/j.cppeds.2022.101313. Epub 2022 Dec 5.
Engelen M, van Ballegoij WJC, Mallack EJ, Van Haren KP, Köhler W, Salsano E, van Trotsenburg ASP, Mochel F, Sevin C, Regelmann MO, Tritos NA, Halper A, Lachmann RH, Davison J, Raymond GV, Lund TC, Orchard PJ, Kuehl JS, Lindemans CA, Caruso P, Turk BR, Moser AB, Vaz FM, Ferdinandusse S, Kemp S, Fatemi A, Eichler FS, Huffnagel IC. International Recommendations for the Diagnosis and Management of Patients With Adrenoleukodystrophy: A Consensus-Based Approach. Neurology. 2022 Nov 22;99(21):940-951. doi: 10.1212/WNL.0000000000201374. Epub 2022 Sep 29.
Harting I, Garbade SF, Rosendaal SD, Mohr A, Sherbini O, Vanderver A, Wolf NI. Identification of PMD subgroups using a myelination score for PMD. Eur J Paediatr Neurol. 2022 Nov;41:71-79. doi: 10.1016/j.ejpn.2022.10.003. Epub 2022 Nov 4.
Eichler F, Sevin C, Barth M, Pang F, Howie K, Walz M, Wilds A, Calcagni C, Chanson C, Campbell L. Understanding caregiver descriptions of initial signs and symptoms to improve diagnosis of metachromatic leukodystrophy. Orphanet J Rare Dis. 2022 Oct 4;17(1):370. doi: 10.1186/s13023-022-02518-z.
Gavazzi F, Pierce SR, Vithayathil J, Cunningham K, Anderson K, McCann J, Moll A, Muirhead K, Sherbini O, Prange E, Dubbs H, Tochen L, Fraser J, Helbig I, Lewin N, Thakur N, Adang LA. Psychometric outcome measures in beta-propeller protein-associated neurodegeneration (BPAN). Mol Genet Metab. 2022 Sep-Oct;137(1-2):26-32. doi: 10.1016/j.ymgme.2022.07.009. Epub 2022 Jul 20.
Helman G, Takanohashi A, Hagemann TL, Perng MD, Walkiewicz M, Woidill S, Sase S, Cross Z, Du Y, Zhao L, Waldman A, Haake BC, Fatemi A, Brenner M, Sherbini O, Messing A, Vanderver A, Simons C. Type II Alexander disease caused by splicing errors and aberrant overexpression of an uncharacterized GFAP isoform. Hum Mutat. 2022 Sep;43(9):1344. doi: 10.1002/humu.24400.
Stutterd CA, Vanderver A, Lockhart PJ, Helman G, Pope K, Uebergang E, Love C, Delatycki MB, Thorburn D, Mackay MT, Peters H, Kornberg AJ, Patel C, Rodriguez-Casero V, Waak M, Silberstein J, Sinclair A, Nolan M, Field M, Davis MR, Fahey M, Scheffer IE, Freeman JL, Wolf NI, Taft RJ, van der Knaap MS, Simons C, Leventer RJ. Unclassified white matter disorders: A diagnostic journey requiring close collaboration between clinical and laboratory services. Eur J Med Genet. 2022 Sep;65(9):104551. doi: 10.1016/j.ejmg.2022.104551. Epub 2022 Jul 5.
Adang L. Leukodystrophies. Continuum (Minneap Minn). 2022 Aug 1;28(4):1194-1216. doi: 10.1212/CON.0000000000001130.
Wongkittichote P, Magistrati M, Shimony JS, Smyser CD, Fatemi SA, Fine AS, Bellacchio E, Dallabona C, Shinawi M. Functional analysis of missense DARS2 variants in siblings with leukoencephalopathy with brain stem and spinal cord involvement and lactate elevation. Mol Genet Metab. 2022 Aug;136(4):260-267. doi: 10.1016/j.ymgme.2022.07.002. Epub 2022 Jul 5.
Alves CAPF, Sherbini O, D'Arco F, Steel D, Kurian MA, Radio FC, Ferrero GB, Carli D, Tartaglia M, Balci TB, Powell-Hamilton NN, Schrier Vergano SA, Reutter H, Hoefele J, Günthner R, Roeder ER, Littlejohn RO, Lessel D, Lüttgen S, Kentros C, Anyane-Yeboa K, Catarino CB, Mercimek-Andrews S, Denecke J, Lyons MJ, Klopstock T, Bhoj EJ, Bryant L, Vanderver A. Brain Abnormalities in Patients with Germline Variants in H3F3: Novel Imaging Findings and Neurologic Symptoms Beyond Somatic Variants and Brain Tumors. AJNR Am J Neuroradiol. 2022 Jul;43(7):1048-1053. doi: 10.3174/ajnr.A7555. Epub 2022 Jun 30.
Adang LA, Gavazzi F, D'Aiello R, Isaacs D, Bronner N, Arici ZS, Flores Z, Jan A, Scher C, Sherbini O, Behrens EM, Goldbach-Mansky R, Olson TS, Lambert MP, Sullivan KE, Teachey DT, Witmer C, Vanderver A, Shults J. Hematologic abnormalities in Aicardi Goutières Syndrome. Mol Genet Metab.. 2022 Jun 16:S1096-7192(22)00339-0. doi: 10.1016/j.ymgme.2022.06.003. Epub ahead of print. PMID: 35786528.
Aicardi Goutières syndrome (AGS) is an inherited disease that is associated with early onset neurologic disability and systemic inflammation. Cytopenias—conditions in which there are lower-than-normal numbers of blood cells—are a potentially serious, but poorly understood, complication of AGS. As new treatment options are developed, it is important to understand the roles of the disease versus the treatment in hematologic abnormalities, allowing for better management of cytopenia. In this study, researchers identified novel patterns of hematologic abnormalities in AGS. The team collected laboratory data throughout the lifespan from 142 individuals with AGS. Results showed that AGS results in multilineage cytopenias not limited to the neonatal period. Neutropenia, anemia, and thrombocytopenia were common. For patients on the treatment baricitinib, moderate to severe graded events of neutropenia, anemia, and leukopenia were more common, but rarely of clinical consequence. Based on these results, authors recommend careful monitoring of hematologic parameters in children with AGS throughout the lifespan, especially while on therapy. Authors also note that AGS should be considered in children with neurologic impairment of unclear cause and hematologic abnormalities.
Mallack EJ, Van Haren KP, Torrey A, van de Stadt S, Engelen M, Raymond GV, Fatemi A, Eichler FS. Presymptomatic Lesion in Childhood Cerebral Adrenoleukodystrophy: Timing and Treatment. Neurology. 2022 May 24:10.1212/WNL.0000000000200571. doi: 10.1212/WNL.0000000000200571. Online ahead of print.
Cetin Gedik K, Lamot L, Romano M, Demirkaya E, Piskin D, Torreggiani S, Adang LA, Armangue T, Barchus K, Cordova DR, Crow YJ, Dale RC, Durrant KL, Eleftheriou D, Fazzi EM, Gattorno M, Gavazzi F, Hanson EP, Lee-Kirsch MA, Montealegre Sanchez GA, Neven B, Orcesi S, Ozen S, Poli MC, Schumacher E, Tonduti D, Uss K, Aletaha D, Feldman BM, Vanderver A, Brogan PA, Goldbach-Mansky R. The 2021 European Alliance of Associations for Rheumatology/American College of Rheumatology points to consider for diagnosis and management of autoinflammatory type I interferonopathies: CANDLE/PRAAS, SAVI and AGS. Ann Rheum Dis. 2022 May;81(5):601-613. doi: 10.1136/annrheumdis-2021-221814. Epub 2022 Jan 27.
Casas-Alba D, Darling A, Caballero E, Mensa-Vilaró A, Bartrons J, Antón J, García-Cazorla À, Vanderver A, Armangué T. Efficacy of baricitinib on chronic pericardial effusion in a patient with Aicardi-Goutières syndrome. Rheumatology (Oxford). 2022 Apr 11;61(4):e87-e89. doi: 10.1093/rheumatology/keab860.
Stellingwerff MD, Nulton C, Helman G, Roosendaal SD, Benko WS, Pizzino A, Bugiani M, Vanderver A, Simons C, van der Knaap MS. Early-Onset Vascular Leukoencephalopathy Caused by Bi-Allelic NOTCH3 Variants. Neuropediatrics. 2022 Apr;53(2):115-121. doi: 10.1055/a-1739-2722. Epub 2022 Jan 13. PMID: 35026854.
Macintosh J, Derksen A, Poulin C, Braverman N, Vanderver A, Thiffault I, Albrecht S, Bernard G. Novel biallelic variants in NRROS associated with a lethal microgliopathy, brain calcifications, and neurodegeneration. Neurogenetics. 2022 Apr;23(2):151-156. doi: 10.1007/s10048-022-00683-8. Epub 2022 Jan 31. PMID: 35099671.
Bonkowsky JL, Wilkes J. Time to Transplant in X-Linked Adrenoleukodystrophy. J Child Neurol.. 2022 Apr;37(5):397-400. doi: 10.1177/08830738221081141. Epub 2022 Mar 3.
Smith Fine A, Kaufman M, Goodman J, Turk B, Bastian A, Lin D, Fatemi A, Keller J. Wearable sensors detect impaired gait and coordination in LBSL during remote assessments. Ann Clin Transl Neurol. 2022 Apr;9(4):468-477. doi: 10.1002/acn3.51509. Epub 2022 Mar 8.
Winkelman JW, Grant NR, Molay F, Stephen CD, Sadjadi R, Eichler FS. Restless Legs Syndrome in X-linked adrenoleukodystrophy. Sleep Med. 2022 Mar;91:31-34. doi: 10.1016/j.sleep.2022.02.008. Epub 2022 Feb 16. PMID: 35245789; PMCID: PMC9035065.
Keller JL, Eloyan A, Raymond GV, Fatemi A, Zackowski KM. Sensorimotor outcomes in adrenomyeloneuropathy show significant disease progression. J Inherit Metab Dis. 2022 Mar;45(2):308-317. doi: 10.1002/jimd.12457. Epub 2021 Dec 9. PMID: 34796974; PMCID: PMC8987487.
Papapetropoulos S, Pontius A, Finger E, Karrenbauer V, Lynch DS, Brennan M, Zappia S, Koehler W, Schoels L, Hayer SN, Konno T, Ikeuchi T, Lund T, Orthmann-Murphy J, Eichler F, Wszolek ZK. Adult-Onset Leukoencephalopathy With Axonal Spheroids and Pigmented Glia: Review of Clinical Manifestations as Foundations for Therapeutic Development. Front Neurol. 2022 Feb 3;12:788168. doi: 10.3389/fneur.2021.788168. eCollection 2021.
van der Knaap MS, Bonkowsky JL, Vanderver A, Schiffmann R, Krägeloh-Mann I, Bertini E, Bernard G, Fatemi SA, Wolf NI, Saunier-Vivar E, Rauner R, Dekker H, van Bokhoven P, van de Ven P, Leferink PS. Therapy Trial Design in Vanishing White Matter: An Expert Consortium Opinion. Neurol Genet. 2022 Feb 2;8(2):e657. doi: 10.1212/NXG.0000000000000657. eCollection 2022 Apr.
Gavazzi F, Fraser JL, Bloom M, Tochen L, Rhee J, Kwan M, Victoria T, Teachey DT, Ho CY, Vanderver A, Linn RL. Hodgkin lymphoma in an individual with TREX1-mediated Aicardi Goutières syndrome. Pediatr Blood Cancer. 2022 Jan;69(1):e29322. doi: 10.1002/pbc.29322. Epub 2021 Sep 7.
Ghabash G, Wilkes J, Barney BJ, Bonkowsky JL. Hospitalization Burden and Incidence of Krabbe Disease. J Child Neurol. 2022 Jan;37(1):12-19. doi: 10.1177/08830738211027717. Epub 2021 Oct 20.
Muirhead KJ, Clause AR, Schlachetzki Z, Dubbs H, Perry DL, Hagelstrom RT, Taft RJ, Vanderver A. Genome sequencing identifies three molecular diagnoses including a mosaic variant in the COL2A1 gene in an individual with Pol III-related leukodystrophy and Feingold syndrome. Cold Spring Harb Mol Case Stud. 2021 Dec 9;7(6):a006143. doi: 10.1101/mcs.a006143. Print 2021 Dec.
Waldman AT, Benson L, Sollee JR, Lavery AM, Liu GW, Green AJ, Waubant E, Heidary G, Conger D, Graves J, Greenberg B. Interocular Difference in Retinal Nerve Fiber Layer Thickness Predicts Optic Neuritis in Pediatric-Onset Multiple Sclerosis. J Neuroophthalmol. 2021 Dec 1;41(4):469-475. doi: 10.1097/WNO.0000000000001070.
Gavazzi F, Cross ZM, Woidill S, McMann JM, Rand EB, Takanohashi A, Ulrick N, Shults J, Vanderver AL, Adang L. Hepatic Involvement in Aicardi-Goutières Syndrome. Neuropediatrics. 2021 Dec;52(6):441-447. doi: 10.1055/s-0040-1722673. Epub 2021 Jan 14.
Gavazzi F, Adang L, Waldman A, Jan AK, Liu G, Lorch SA, DeMauro SB, Shults J, Pierce SR, Ballance E, Kornafel T, Harrington A, Glanzman AM, Vanderver A. Reliability of the Telemedicine Application of the Gross Motor Function Measure-88 in Patients With Leukodystrophy. Pediatr Neurol. 2021 Dec;125:34-39. doi: 10.1016/j.pediatrneurol.2021.09.012. Epub 2021 Sep 24. PMID: 34624609; PMCID: PMC8629609.
Ghabash G, Wilkes J, Bonkowsky JL. National U.S. Patient and Transplant Data for Krabbe Disease. Front Pediatr. 2021 Nov 11;9:764626. doi: 10.3389/fped.2021.764626. eCollection 2021.
Mallack EJ, Askin G, van de Stadt S, Caruso PA, Musolino PL, Engelen M, Niogi SN, Eichler FS. A Longitudinal Analysis of Early Lesion Growth in Presymptomatic Patients with Cerebral Adrenoleukodystrophy. AJNR Am J Neuroradiol. 2021 Oct;42(10):1904-1911. doi: 10.3174/ajnr.A7250. Epub 2021 Sep 9.
Malhotra A, Ziegler A, Shu L, Perrier R, Amlie-Wolf L, Wohler E, Lygia de Macena Sobreira N, Colin E, Vanderver A, Sherbini O, Stouffs K, Scalais E, Serretti A, Barth M, Navet B, Rollier P, Xi H, Wang H, Zhang H, Perry DL, Ferrarini A, Colombo R, Pepler A, Schneider A, Tomiwa K, Okamoto N, Matsumoto N, Miyake N, Taft R, Mao X, Bonneau D. De novo missense variants in LMBRD2 are associated with developmental and motor delays, brain structure abnormalities and dysmorphic features. J Med Genet. 2021 Oct;58(10):712-716. doi: 10.1136/jmedgenet-2020-107137. Epub 2020 Aug 20.
Barczykowski AL, Langan TJ, Vanderver A, Jalal K, Carter RL. Death rates in the U.S. due to Leukodystrophies with pediatric forms. Am J Med Genet A. 2021 Aug;185(8):2361-2373. doi: 10.1002/ajmg.a.62248. Epub 2021 May 7.
Helman G, Zerem A, Almad A, Hacker JL, Woidill S, Sase S, LeFevre AN, Ekstein J, Johansson MM, Stutterd CA, Taft RJ, Simons C, Grinspan JB, Pizzino A, Schmidt JL, Harding B, Hirsch Y, Viaene AN, Fattal-Valevski A, Vanderver A. Further Delineation of the Clinical and Pathologic Features of HIKESHI-Related Hypomyelinating Leukodystrophy. Pediatr Neurol. 2021 Aug;121:11-19. doi: 10.1016/j.pediatrneurol.2021.04.014. Epub 2021 May 14.
Roosendaal SD, van de Brug T, Alves CAPF, Blaser S, Vanderver A, Wolf NI, van der Knaap MS. Imaging Patterns Characterizing Mitochondrial Leukodystrophies. AJNR Am J Neuroradiol. 2021 Jul;42(7):1334-1340. doi: 10.3174/ajnr.A7097. Epub 2021 Apr 1.
Bley A, Denecke J, Kohlschütter A, Schön G, Hischke S, Guder P, Bierhals T, Lau H, Hempel M, Eichler FS. The natural history of Canavan disease: 23 new cases and comparison with patients from literature. Orphanet J Rare Dis. 2021 May 19;16(1):227. doi: 10.1186/s13023-020-01659-3.
Mallack EJ, Turk BR, Yan H, Price C, Demetres M, Moser AB, Becker C, Hollandsworth K, Adang L, Vanderver A, Van Haren K, Ruzhnikov M, Kurtzberg J, Maegawa G, Orchard PJ, Lund TC, Raymond GV, Regelmann M, Orsini JJ, Seeger E, Kemp S, Eichler F, Fatemi A. MRI surveillance of boys with X-linked adrenoleukodystrophy identified by newborn screening: Meta-analysis and consensus guidelines. J Inherit Metab Dis. 2021 May;44(3):728-739. doi: 10.1002/jimd.12356. Epub 2021 Jan 9.
Gavazzi F, Charsar BA, Williams C, Shults J, Alves CA, Adang L, Vanderver A. Acquisition of Developmental Milestones in Hypomyelination With Atrophy of the Basal Ganglia and Cerebellum and Other TUBB4A-Related Leukoencephalopathy. J Child Neurol. 2021 Apr 12:883073821000977. doi: 10.1177/0883073821000977. Online ahead of print.
Weinhofer I, Rommer P, Zierfuss B, Altmann P, Foiani M, Heslegrave A, Zetterberg H, Gleiss A, Musolino PL, Gong Y, Forss-Petter S, Berger T, Eichler F, Aubourg P, Köhler W, Berger J. Neurofilament light chain as a potential biomarker for monitoring neurodegeneration in X-linked adrenoleukodystrophy. Nat Commun. 2021 Mar 22;12(1):1816. doi: 10.1038/s41467-021-22114-2.
Ramirez Alcantara J, Halper A. Adrenal insufficiency updates in children. Curr Opin Endocrinol Diabetes Obes. 2021 Feb 1;28(1):75-81. doi: 10.1097/MED.0000000000000591.
Piccoli C, Bronner N, Gavazzi F, Dubbs H, De Simone M, De Giorgis V, Orcesi S, Fazzi E, Galli J, Masnada S, Tonduti D, Varesio C, Vanderver A, Vossough A, Adang L. Late-Onset Aicardi-Goutières Syndrome: A Characterization of Presenting Clinical Features. Pediatr Neurol. 2021 Feb;115:1-6. doi: 10.1016/j.pediatrneurol.2020.10.012. Epub 2020 Nov 2.
Pelletier F, Perrier S, Cayami FK, Mirchi A, Saikali S, Tran LT, Ulrick N, Guerrero K, Rampakakis E, van Spaendonk RML, Naidu S, Pohl D, Gibson WT, Demos M, Goizet C, Tejera-Martin I, Potic A, Fogel BL, Brais B, Sylvain M, Sébire G, Lourenço CM, Bonkowsky JL, Catsman-Berrevoets C, Pinto PS, Tirupathi S, Strømme P, de Grauw T, Gieruszczak-Bialek D, Krägeloh-Mann I, Mierzewska H, Philippi H, Rankin J, Atik T, Banwell B, Benko WS, Blaschek A, Bley A, Boltshauser E, Bratkovic D, Brozova K, Cimas I, Clough C, Corenblum B, Dinopoulos A, Dolan G, Faletra F, Fernandez R, Fletcher J, Garcia Garcia ME, Gasparini P, Gburek-Augustat J, Gonzalez Moron D, Hamati A, Harting I, Hertzberg C, Hill A, Hobson GM, Innes AM, Kauffman M, Kirwin SM, Kluger G, Kolditz P, Kotzaeridou U, La Piana R, Liston E, McClintock W, McEntagart M, McKenzie F, Melançon S, Misbahuddin A, Suri M, Monton FI, Moutton S, Murphy RPJ, Nickel M, Onay H, Orcesi S, Özkınay F, Patzer S, Pedro H, Pekic S, Pineda Marfa M, Pizzino A, Plecko B, Poll-The BT, Popovic V, Rating D, Rioux MF, Rodriguez Espinosa N, Ronan A, Ostergaard JR, Rossignol E, Sanchez-Carpintero R, Schossig A, Senbil N, Sønderberg Roos LK, Stevens CA, Synofzik M, Sztriha L, et al. Endocrine and Growth Abnormalities in 4H Leukodystrophy Caused by Variants in POLR3A, POLR3B, and POLR1C. J Clin Endocrinol Metab. 2021 Jan 23;106(2):e660-e674. doi: 10.1210/clinem/dgaa700.
Engelen M, Kemp S, Eichler F. Endocrine dysfunction in adrenoleukodystrophy. Handb Clin Neurol. 2021;182:257-267. doi: 10.1016/B978-0-12-819973-2.00018-6.
Adang L, Goldbach-Mansky R, Vanderver A. JAK Inhibition in the Aicardi-Goutières Syndrome. Reply. N Engl J Med. 2020 Nov 26;383(22):2191-2193. doi: 10.1056/NEJMc2031081.
Lewis H, Samanta D, Örsell JL, Bosanko KA, Rowell A, Jones M, Dale RC, Taravath S, Hahn CD, Krishnakumar D, Chagnon S, Keller S, Hagebeuk E, Pathak S, Bebin EM, Arndt DH, Alexander JJ, Mainali G, Coppola G, Maclean J, Sparagana S, McNamara N, Smith DM, Raggio V, Cruz M, Fernández-Jaén A, Kava MP, Emrick L, Fish JL, Vanderver A, Helman G, Pierson TM, Zarate YA. Epilepsy and Electroencephalographic Abnormalities in SATB2-Associated Syndrome. Pediatr Neurol. 2020 Nov;112:94-100. doi: 10.1016/j.pediatrneurol.2020.04.006. Epub 2020 Apr 13.
Grineski SE, Morales DX, Collins T, Wilkes J, Bonkowsky JL. Racial/Ethnic and Insurance Status Disparities in Distance Traveled to Access Children's Hospital Care for Severe Illness: the Case of Children with Leukodystrophies. J Racial Ethn Health Disparities. 2020 Oct;7(5):975-986. doi: 10.1007/s40615-020-00722-w. Epub 2020 Feb 24.
Vanderver A, Adang L, Gavazzi F, McDonald K, Helman G, Frank DB, Jaffe N, Yum SW, Collins A, Keller SR, Lebon P, Meritet JF, Rhee J, Takanohashi A, Armangue T, Ulrick N, Sherbini O, Koh J, Peer K, Besnier C, Scher C, Boyle K, Dubbs H, Kramer-Golinkoff J, Pizzino A, Woidill S, Shults J. Janus Kinase Inhibition in the Aicardi-Goutières Syndrome. N Engl J Med. 2020 Sep 3;383(10):986-989. doi: 10.1056/NEJMc2001362.
Schmidt JL, Pizzino A, Nicholl J, Foley A, Wang Y, Rosenfeld JA, Mighion L, Bean L, da Silva C, Cho MT, Truty R, Garcia J, Speare V, Blanco K, Powis Z, Hobson GM, Kirwin S, Krock B, Lee H, Deignan JL, Westemeyer MA, Subaran RL, Thiffault I, Tsai EA, Fang T, Helman G, Vanderver A. Estimating the relative frequency of leukodystrophies and recommendations for carrier screening in the era of next-generation sequencing. Am J Med Genet A. 2020 Aug;182(8):1906-1912. doi: 10.1002/ajmg.a.61641. Epub 2020 Jun 23.
Vanderver A, Bernard G, Helman G, Sherbini O, Boeck R, Cohn J, Collins A, Demarest S, Dobbins K, Emrick L, Fraser JL, Masser-Frye D, Hayward J, Karmarkar S, Keller S, Mirrop S, Mitchell W, Pathak S, Sherr E, van Haren K, Waters E, Wilson JL, Zhorne L, Schiffmann R, van der Knaap MS, Pizzino A, Dubbs H, Shults J, Simons C, Taft RJ; LeukoSEQ Workgroup. Randomized Clinical Trial of First-Line Genome Sequencing in Pediatric White Matter Disorders. Ann Neurol. 2020 Aug;88(2):264-273. doi: 10.1002/ana.25757. Epub 2020 Jun 9.
Adang LA, Gavazzi F, Jawad AF, Cusack SV, Kopin K, Peer K, Besnier C, De Simone M, De Giorgis V, Orcesi S, Fazzi E, Galli J, Shults J, Vanderver A. Development of a neurologic severity scale for Aicardi Goutières Syndrome. Mol Genet Metab. 2020 Jun;130(2):153-160. doi: 10.1016/j.ymgme.2020.03.008. Epub 2020 Apr 2.
Helman G, Takanohashi A, Hagemann TL, Perng MD, Walkiewicz M, Woidill S, Sase S, Cross Z, Du Y, Zhao L, Waldman A, Haake BC, Fatemi A, Brenner M, Sherbini O, Messing A, Vanderver A, Simons C. Type II Alexander disease caused by splicing errors and aberrant overexpression of an uncharacterized GFAP isoform. Hum Mutat. 2020 Jun;41(6):1131-1137. doi: 10.1002/humu.24008. Epub 2020 Mar 11.
Wolf NI, Breur M, Plug B, Beerepoot S, Westerveld ASR, van Rappard DF, de Vries SI, Kole MHP, Vanderver A, van der Knaap MS, Lindemans CA, van Hasselt PM, Boelens JJ, Matzner U, Gieselmann V, Bugiani M. Metachromatic leukodystrophy and transplantation: remyelination, no cross-correction. Ann Clin Transl Neurol. 2020 Feb;7(2):169-180. doi: 10.1002/acn3.50975. Epub 2020 Jan 22.
Helman G, Lajoie BR, Crawford J, Takanohashi A, Walkiewicz M, Dolzhenko E, Gross AM, Gainullin VG, Bent SJ, Jenkinson EM, Ferdinandusse S, Waterham HR, Dorboz I, Bertini E, Miyake N, Wolf NI, Abbink TEM, Kirwin SM, Tan CM, Hobson GM, Guo L, Ikegawa S, Pizzino A, Schmidt JL, Bernard G, Schiffmann R, van der Knaap MS, Simons C, Taft RJ, Vanderver A. Genome sequencing in persistently unsolved white matter disorders. Ann Clin Transl Neurol. 2020 Jan;7(1):144-152. doi: 10.1002/acn3.50957. Epub 2020 Jan 7.
Mendes MI, Green LMC, Bertini E, Tonduti D, Aiello C, Smith D, Salsano E, Beerepoot S, Hertecant J, von Spiczak S, Livingston JH, Emrick L, Fraser J, Russell L, Bernard G, Magri S, Di Bella D, Taroni F, Koenig MK, Moroni I, Cappuccio G, Brunetti-Pierri N, Rhee J, Mendelsohn BA, Helbig I, Helbig K, Muhle H, Ismayl O, Vanderver AL, Salomons GS, van der Knaap MS, Wolf NI. RARS1-related hypomyelinating leukodystrophy: Expanding the spectrum. Ann Clin Transl Neurol. 2020 Jan;7(1):83-93. doi: 10.1002/acn3.50960. Epub 2019 Dec 8.
Bursle C, Yiu EM, Yeung A, Freeman JL, Stutterd C, Leventer RJ, Vanderver A, Yaplito-Lee J. Hyperinsulinaemic hypoglycaemia: A rare association of vanishing white matter disease. JIMD Rep. 2019 Nov 12;51(1):11-16. doi: 10.1002/jmd2.12081. eCollection 2020 Jan.
Gauquelin L, Cayami FK, Sztriha L, Yoon G, Tran LT, Guerrero K, Hocke F, van Spaendonk RML, Fung EL, D'Arrigo S, Vasco G, Thiffault I, Niyazov DM, Person R, Lewis KS, Wassmer E, Prescott T, Fallon P, McEntagart M, Rankin J, Webster R, Philippi H, van de Warrenburg B, Timmann D, Dixit A, Searle C; DDD Study,; Thakur N, Kruer MC, Sharma S, Vanderver A, Tonduti D, van der Knaap MS, Bertini E, Goizet C, Fribourg S, Wolf NI, Bernard G. Clinical spectrum of POLR3-related leukodystrophy caused by biallelic POLR1C pathogenic variants. Neurol Genet. 2019 Oct 30;5(6):e369. doi: 10.1212/NXG.0000000000000369. eCollection 2019 Dec.
Zarate YA, Bosanko KA, Caffrey AR, Bernstein JA, Martin DM, Williams MS, Berry-Kravis EM, Mark PR, Manning MA, Bhambhani V, Vargas M, Seeley AH, Estrada-Veras JI, van Dooren MF, Schwab M, Vanderver A, Melis D, Alsadah A, Sadler L, Van Esch H, Callewaert B, Oostra A, Maclean J, Dentici ML, Orlando V, Lipson M, Sparagana SP, Maarup TJ, Alsters SI, Brautbar A, Kovitch E, Naidu S, Lees M, Smith DM, Turner L, Raggio V, Spangenberg L, Garcia-Miñaúr S, Roeder ER, Littlejohn RO, Grange D, Pfotenhauer J, Jones MC, Balasubramanian M, Martinez-Monseny A, Blok LS, Gavrilova R, Fish JL. Mutation update for the SATB2 gene. Hum Mutat. 2019 Aug;40(8):1013-1029. doi: 10.1002/humu.23771. Epub 2019 Jun 18.
Guo L, Bertola DR, Takanohashi A, Saito A, Segawa Y, Yokota T, Ishibashi S, Nishida Y, Yamamoto GL, Franco JFDS, Honjo RS, Kim CA, Musso CM, Timmons M, Pizzino A, Taft RJ, Lajoie B, Knight MA, Fischbeck KH, Singleton AB, Ferreira CR, Wang Z, Yan L, Garbern JY, Simsek-Kiper PO, Ohashi H, Robey PG, Boyde A, Matsumoto N, Miyake N, Spranger J, Schiffmann R, Vanderver A, Nishimura G, Passos-Bueno MRDS, Simons C, Ishikawa K, Ikegawa S. Bi-allelic CSF1R Mutations Cause Skeletal Dysplasia of Dysosteosclerosis-Pyle Disease Spectrum and Degenerative Encephalopathy with Brain Malformation. Am J Hum Genet. 2019 May 2;104(5):925-935. doi: 10.1016/j.ajhg.2019.03.004. Epub 2019 Apr 11.
Al Yazidi G, Tran LT, Guerrero K, Vanderver A, Schiffmann R, Wolf NI, Chouinard S, Bernard G. Dystonia in RNA Polymerase III-Related Leukodystrophy. Mov Disord Clin Pract. 2019 Jan 9;6(2):155-159. doi: 10.1002/mdc3.12715. eCollection 2019 Feb.
Stutterd CA, Lake NJ, Peters H, Lockhart PJ, Taft RJ, van der Knaap MS, Vanderver A, Thorburn DR, Simons C, Leventer RJ. Severe Leukoencephalopathy with Clinical Recovery Caused by Recessive BOLA3 Mutations. JIMD Rep. 2019;43:63-70. doi: 10.1007/8904_2018_100. Epub 2018 Apr 14.
Köhler W, Curiel J, Vanderver A. Adulthood leukodystrophies. Nat Rev Neurol. 2018 Feb;14(2):94-105. doi: 10.1038/nrneurol.2017.175. Epub 2018 Jan 5.
Jenkinson EM, Rodero MP, Kasher PR, Uggenti C, Oojageer A, Goosey LC, Rose Y, Kershaw CJ, Urquhart JE, Williams SG, Bhaskar SS, O'Sullivan J, Baerlocher GM, Haubitz M, Aubert G, Barañano KW, Barnicoat AJ, Battini R, Berger A, Blair EM, Brunstrom-Hernandez JE, Buckard JA, Cassiman DM, Caumes R, Cordelli DM, De Waele LM, Fay AJ, Ferreira P, Fletcher NA, Fryer AE, Goel H, Hemingway CA, Henneke M, Hughes I, Jefferson RJ, Kumar R, Lagae L, Landrieu PG, Lourenço CM, Malpas TJ, Mehta SG, Metz I, Naidu S, Õunap K, Panzer A, Prabhakar P, Quaghebeur G, Schiffmann R, Sherr EH, Sinnathuray KR, Soh C, Stewart HS, Stone J, Van Esch H, Van Mol CE, Vanderver A, Wakeling EL, Whitney A, Pavitt GD, Griffiths-Jones S, Rice GI, Revy P, van der Knaap MS, Livingston JH, O'Keefe RT, Crow YJ. Corrigendum: Mutations in SNORD118 cause the cerebral microangiopathy leukoencephalopathy with calcifications and cysts. Nat Genet. 2017 Jan 31;49(2):317. doi: 10.1038/ng0217-317b.
Khani-Habibabadi F, Roy B, Pham MC, Obaid AH, Filipek B, Nowak RJ, O'Connor KC. AChR Autoantibody Pathogenic Properties Are Heterogeneously Distributed and Undergo Temporal Changes Among Patients With Myasthenia Gravis. Neurol Neuroimmunol Neuroinflamm. 2025 Sep;12(5):e200436. doi: 10.1212/NXI.0000000000200436. Epub 2025 Jul 18. PMID: 40680247; PMCID: PMC12275905.
Myasthenia gravis (MG) is a neuromuscular disorder caused by an autoimmune response which blocks or damages the neuromuscular junction in muscles, causing disabling weakness with characteristic fluctuation in severity over time. The most common form of MG is caused by acetylcholine receptor (AChR) autoantibodies, which either block the AChR, increase their removal from the muscle surface, or block complement.
In this study, researchers investigated the pathogenic properties of AChR autoantibodies in MG and whether they varied over time in relationship to severity of disease. The team analyzed serum specimens from 50 patients with MG collected every six months for two years. Next, they used live cell-based assays to measure AChR autoantibody isotypes, immunoglobulin G subclasses, and the nature of the pathogenic mechanisms.
Results showed that the pathogenic mechanisms of the antibodies fluctuated over time and were generally not associated with disease severity. Authors concluded that additional studies of autoantibody pathogenicity should be incorporated into MG clinical trials to assess differential treatment responses.
Sikorski PM, Kaminski HJ, Vincent A, Bauman T, Jacobson L, Kusner LL. Subtype-specific atypical B cell profiles in myasthenia gravis reveal distinct immunopathological pathways. Front Immunol. 2025 Jun 18;16:1608160. doi: 10.3389/fimmu.2025.1608160. PMID: 40607384; PMCID: PMC12213399.
Myasthenia gravis (MG) is a neuromuscular disorder caused by an autoimmune response which blocks or damages acetylcholine receptors (AChR) in muscles, causing disabling weakness. Subtypes of MG—AChR-positive MG and muscle-specific kinase (MuSK)-positive MG—have different immune responses that may be caused by atypical B cells, an emerging subset of immune cells implicated in autoimmunity.
In this study, researchers explored the effect of atypical B cells on immune response in MG. The team used spectral flow cytometry to analyze atypical B cells in individuals with AChR-MG and MuSK-MG as well as healthy controls.
Results revealed that MG subtypes show distinct atypical B cell profiles that are linked to immunopathology and disease onset. Authors note that these findings highlight the potential for atypical B cells as therapeutic targets in both immunoglobin G1-3- and immunoglobin G4-mediated autoimmunity.
Spagni G, Verza MU, Cornacchini S, Beretta F, Sun B, Lotti A, Falso S, Barilaro A, Massacesi L, Evoli A, Damato V. Validation of the "Patient-Acceptable Symptom State" Question as Outcome Measure in AChR Myasthenia Gravis: A Multicentre, Prospective Study. Eur J Neurol. 2025 Jun;32(6):e70262. doi: 10.1111/ene.70262. PMID: 40556475; PMCID: PMC12188101.
Myasthenia gravis (MG) is a neuromuscular disorder caused by an autoimmune response which blocks or damages acetylcholine receptors in muscles, causing disabling weakness. New treatments have recently emerged for acetylcholine receptor (AChR) antibody-positive MG (AChR-MG). However, not all patients experience significant improvement, highlighting the importance of including the patient perspective in outcome evaluations.
In this study, researchers validated the Patient-Acceptable Symptom State (PASS) question as an outcome measure in AChR-MG. The team analyzed PASS responses among 173 patients with AChR-MG.
Results confirmed the PASS question as an effective, concise tool to assess AChR-MG patients' satisfaction with their disease control. Authors note that these findings also highlight the relevance of ocular complaints in patients' perception of MG burden.
Leach JM, Aban I, Cutter G, Benatar M. Handling rescue therapy in myasthenia gravis clinical trials: why it matters and why you should care. Ann Clin Transl Neurol. 2025 May;12(5):888-897. doi: 10.1002/acn3.52309. Epub 2025 Apr 16. PMID: 40241261; PMCID: PMC12093330.
Myasthenia gravis (MG) is a neuromuscular disorder caused by an autoimmune response which blocks or damages acetylcholine receptors in muscles, causing disabling weakness. Clinical trials for MG aim to evaluate whether a new therapy can improve patients’ symptoms. However, if a study participant experiences worsening symptoms, they typically receive existing therapies to improve their condition. This type of intervention, called “rescue therapy,” could lead to inaccurate information if not appropriately addressed.
In this review, researchers discuss the impact of rescue therapy in MG clinical trials. The team reviews strategies for incorporating rescue therapy in the design and statistical analysis of MG trials, shows how each strategy affects the interpretation of trial results, and suggests circumstances when each strategy may or may not be applicable to patients or physicians.
Authors note that rescue therapy should be considered during the planning phase of clinical trials before designing the statistical analysis, which can improve the robustness of the study and alignment with regulatory recommendations.
Garbey M, Lesport Q, Kaminski HJ. Construction of patient trajectories to model clinical trial outcomes: Application to Myasthenia Gravis. medRxiv [Preprint]. 2025 Apr 16:2025.04.11.25325663. doi: 10.1101/2025.04.11.25325663
Bauman TA, Lee SM, Juel VC, Li Y, Gilbert K, Chen J, Kaminski HJ, Kusner LL; MGNet Investigators. Serum fibrinogen is not elevated in patients with myasthenia gravis. Sci Rep. 2025 Apr 15;15(1):13013. doi: 10.1038/s41598-025-97599-8.
Chang EL, Liu R, Keyhanian K, Huynh K, Berkenstock M, Bhatti MT, Chen JJ, Chodosh J, Costello F, Dalvin LA, DeLott LB, Dinkin M, Egan RA, Fraser CL, Freitag SK, Gangaputra S, Gordon LK, Guidon AC, Johnson DB, Kombo N, Kramer M, Lee AG, Levy M, Lobo-Chan AM, Mantopoulos D, Papaliodis G, Pless M, Pimkina J, Rubin KM, Sen HN, Shariff A, Subramanian PS, Tsui E, Yoon MK, McDunn J, Rine J, Reynolds KL, Sobrin L, Chwalisz BK. Consensus disease definitions for ophthalmic immune-related adverse events of immune checkpoint inhibitors. J Immunother Cancer. 2025 Apr 8;13(4):e011049. doi: 10.1136/jitc-2024-011049.
Garbey M, Lesport Q, Girma H, Öztosun G, Kaminski HJ. A Quantitative Study of Factors Influencing Myasthenia Gravis Telehealth Examination Score. Muscle Nerve. 2025 Jul;72(1):34-41. doi: 10.1002/mus.28394. Epub 2025 Apr 2. PMID: 40176335; PMCID: PMC12140879.
Myasthenia gravis (MG) is a neuromuscular disorder caused by an autoimmune response which blocks or damages acetylcholine receptors in muscles, causing disabling weakness. Although telemedicine is considered a positive tool for both MG patients and physicians, not much is known about its strengths and limitations for MG examinations.
In this study, researchers developed an artificial intelligence-based assessment of telehealth examinations in MG. The team studied video recordings of 51 patients with MG who completed two telemedicine-based examinations with neuromuscular experts. Researchers applied artificial intelligence algorithms including computer vision, speech analysis, and natural language processing to assess the reproducibility and reliability of the examinations.
Results showed that overall MG core examination scores were consistent across examiners. However, individual metrics showed up to 25% variability due to differences in examiner instructions, video recording limitations, and patient disease severity. Authors note that further refinement of this technology could enhance examiner training and reduce variability in clinical trial outcome measures.
Bril V, Drużdż A, Grosskreutz J, Habib AA, Kaminski HJ, Mantegazza R, Sacconi S, Utsugisawa K, Vu T, Boehnlein M, Gayfieva M, Greve B, Woltering F, Vissing J; MG0004 study investigators. Safety and efficacy of chronic weekly rozanolixizumab in generalized myasthenia gravis: the randomized open-label extension MG0004 study. J Neurol. 2025 Mar 19;272(4):275. doi: 10.1007/s00415-025-12958-9.
Sabatelli E, Bonagura L, Falso S, Marini S, Papi C, Campetella L, De Maio MM, Iorio R. Light Sensitivity in Myasthenia Gravis: Clinical Characteristics and Impact on Quality of Life. Muscle Nerve. 2025 Mar 5. doi: 10.1002/mus.28386. Online ahead of print.
Chen J, Su C, Feng H, Kaminski HJ. Can Non-Thymomatous Late-Onset Myasthenia Gravis Benefit From Thymectomy? A Systematic Review and Meta-Analysis. Eur J Neurol. 2025 Mar;32(3):e70048. doi: 10.1111/ene.70048.
AlGaeed M, McPherson T, Lee I, Feese M, Aban I, Cutter G, Kaminski HJ, Karroum EG. Prevalence of restless legs and association with patient-reported outcome measures in myasthenia gravis. J Clin Sleep Med. 2025 Feb 1;21(2):269-276. doi: 10.5664/jcsm.11386.
Garbey M, Lesport Q, Girma H, Öztosun G, Abu-Rub M, Guidon AC, Juel V, Nowak RJ, Soliven B, Aban I, Kaminski HJ. Application of digital tools and artificial intelligence in the Myasthenia Gravis Core Examination. Front Neurol. 2024 Dec 4;15:1474884. doi: 10.3389/fneur.2024.1474884. eCollection 2024.
Falso S, Marini S, Carrozza C, Sabatelli E, Mascagna G, Marini M, Morroni J, Evoli A, Iorio R. Concordance between radioimmunoassay and fixed cell-based assay in subjects without myasthenia gravis: optimizing the diagnostic approach. Eur J Neurol. 2024 Dec;31(12):e16435. doi: 10.1111/ene.16435. Epub 2024 Aug 8. PMID: 39118440; PMCID: PMC11554847.
Myasthenia gravis (MG) is a neuromuscular disorder caused by an autoimmune response which blocks or damages acetylcholine receptors in muscles, causing disabling weakness. Acetylcholine receptor antibody detection is crucial for MG diagnosis. Currently, radioimmunoassay is the gold-standard test used to measure the concentration of acetylcholine receptor antibodies. However, this test may detect false positives for nonpathogenic antibodies.
In this study, researchers compared the accuracy of radioimmunoassay and fixed cell-based assay for MG diagnosis. First, the team reviewed medical records of 605 patients who tested positive for acetylcholine receptor antibodies via radioimmunoassay and confirmed these results. Next, the team retested asymptomatic patients via fixed cell-based assay to determine whether this method would show higher accuracy in detecting pathogenic antibodies.
Results show that, in rare cases, fixed cell-based assay may be more specific than radioimmunoassay in detecting pathogenic antibodies. Authors note that fixed cell-based assay may be performed as an additional tool to increase diagnostic accuracy when clinical presentation and electrodiagnostic studies are found to be atypical for MG.
Spagni G, Vincent A, Sun B, Falso S, Jacobson LW, Devenish S, Evoli A, Damato V. Serological Markers of Clinical Improvement in MuSK Myasthenia Gravis. Neurol Neuroimmunol Neuroinflamm. 2024 Nov;11(6):e200313. doi: 10.1212/NXI.0000000000200313. Epub 2024 Sep 9.
Lesport Q, Palmie D, Öztosun G, Kaminski HJ, Garbey M. AI-Powered Telemedicine for Automatic Scoring of Neuromuscular Examinations. Bioengineering (Basel). 2024 Sep 20;11(9):942. doi: 10.3390/bioengineering11090942.
Falso S, Gessi M, Marini S, Benvenuto R, Sabatelli E, D'Amati A, Marini M, Evoli A, Iorio R. Cancer Frequency in MuSK Myasthenia Gravis and Histological Evidence of Paraneoplastic Etiology. Ann Neurol. 2024 Jul 15. doi: 10.1002/ana.27033. Epub ahead of print. PMID: 39007444.
Muscle-specific kinase myasthenia gravis (MuSK-MG) is an autoimmune disorder caused by antibodies targeting the muscle-specific kinase (MuSK), causing muscle weakness. Although neurological autoimmunity can potentially increase the risk of cancer, not much is known about cancer rates among patients with MuSK-MG.
In this study, researchers explored the frequency and timing of cancer in patients with MuSK-MG. The team reviewed records of 94 patients, recording information about diagnosis and treatment of associated cancers. In two patients with MuSK-MG onset after cancer diagnosis, researchers performed immunohistochemistry to assess MuSK expression in cancer cells of tumor specimens.
Assessment of tumor specimens revealed strong nuclear expression of the MuSK protein in cancer cells. These findings suggest a new pathway in the formation of tumors as well as a potential therapeutic target. Authors note that this preliminary study needs to be replicated in a much larger cohort of patients to determine if cancers could be a trigger for MuSK MG.
Kaminski HJ, Sikorski P, Coronel SI, Kusner LL. Myasthenia gravis: the future is here. J Clin Invest. 2024 Jun 17;134(12):e179742. doi: 10.1172/JCI179742. PMCID: PMC11178544.
Myasthenia gravis (MG) is a rare neuromuscular disorder that occurs when the body’s immune system attacks the nerve-muscle communication point, causing disabling weakness. Over the past few decades, understanding of MG has progressed significantly, leading to the development of new therapies.
In this review paper, researchers discuss the current understanding of pathophysiology and new therapies in MG. The team covers the various subgroups of MG as well as emerging therapeutic strategies. Authors note that these insights shed light on the evolving landscape of MG treatment and exciting prospects for further research.
Li Y, Yi JS, Guptill JT, Juel VC, Hobson-Webb L, Raja SM, Karatz T, Gable KL. Immune dysregulation in chronic inflammatory demyelinating polyneuropathy. J Neuroimmunol. 2024 Jun 15;391:578360. doi: 10.1016/j.jneuroim.2024.578360. Epub 2024 May 5.
Bodansky A, Yu DJ, Rallistan A, Kalaycioglu M, Boonyaratanakornkit J, Green DJ, Gauthier J, Turtle CJ, Zorn K, O'Donovan B, Mandel-Brehm C, Asaki J, Kortbawi H, Kung AF, Rackaityte E, Wang CY, Saxena A, de Dios K, Masi G, Nowak RJ, O'Connor KC, Li H, Diaz VE, Saloner R, Casaletto KB, Gontrum EQ, Chan B, Kramer JH, Wilson MR, Utz PJ, Hill JA, Jackson SW, Anderson MS, DeRisi JL. Unveiling the proteome-wide autoreactome enables enhanced evaluation of emerging CAR T cell therapies in autoimmunity. J Clin Invest. 2024 May 16;134(13):e180012. doi: 10.1172/JCI180012. PMID: 38753445; PMCID: PMC11213466.
Autoimmune diseases are a group of conditions caused by a dysregulated immune system that attacks and damages the body. As autoimmune diseases have become increasingly more common, new therapies have emerged. However, how they specifically alter the immune system is not well understood.
In this study, researchers studied the circulating autoantibody repertoire to further understand the effect of therapies used for autoimmune diseases. Leveraging a custom set of over 730,000 human-derived peptides (short chains of amino acids), the team explored variations in autoantibody profiles across individuals who were treated with different immune-modulating therapies.
Results show that each individual—regardless of disease state—has a distinct and complex set of autoantibodies, which creates a unique immunological footprint researchers call the “autoreactome” that remains surprisingly stable over many years. The team found that therapies targeting B cell maturation antigen (BCMA) greatly altered an individual’s autoreactome, while anti-CD19 and anti-CD20 therapies, which deplete B cells, had minimal effects. Authors note that these findings suggest the potential for BCMA therapy in treating autoantibody diseases that are resistant to current therapies.
Yandamuri SS, Filipek B, Lele N, Cohen I, Bennett JL, Nowak RJ, Sotirchos ES, Longbrake EE, Mace EM, O'Connor KC. A Noncanonical CD56dimCD16dim/− NK Cell Subset Indicative of Prior Cytotoxic Activity Is Elevated in Patients with Autoantibody-Mediated Neurologic Diseases. J Immunol. 2024 Mar 1;212(5):785-800. doi: 10.4049/jimmunol.2300015. PMID: 38251887; PMCID: PMC10932911.
Neuromyelitis optica spectrum disorder (NMOSD), myelin oligodendrocyte glycoprotein Ab disease, and autoimmune myasthenia gravis (MG) are autoantibody-mediated autoimmune diseases. Autoantibodies can cause a type of immune reaction called Ab-dependent cellular cytotoxicity (ADCC) involving natural killer (NK) cells. However, it is not known whether ADCC contributes to disease development in patients with these conditions.
In this study, researchers investigated the characteristics of circulating NK cells in patients with NMOSD, myelin oligodendrocyte glycoprotein Ab disease, and MG. The team used functional assays, phenotyping, and transcriptomics to explore the role of NK cells in these diseases.
Results show elevated subsets of NK cells in patients with NMOSD and MG. Authors note that this elevation suggests prior ADCC activity occurring in the affected tissues.
Macaluso M, Rothenberg ME, Ferkol T, Kuhnell P, Kaminski HJ, Kimberlin DW, Benatar M, Chehade M; Principal Investigators of the Rare Diseases Clinical Research Network – Cycle 4. Impact of the COVID-19 Pandemic on People Living With Rare Diseases and Their Families: Results of a National Survey. JMIR Public Health Surveill. 2024 Feb 14;10:e48430. doi: 10.2196/48430.
Vega Prado I, Shymansky J, Apte A, Mortman K, Kaminski HJ, Barak S. A Rare Case of Metaplastic Thymoma Presenting With Myasthenia Gravis. Int J Surg Pathol. 2024 Feb;32(1):155-159. doi: 10.1177/10668969231168344. Epub 2023 Apr 24.
Iorio R. Myasthenia gravis: the changing treatment landscape in the era of molecular therapies. Nat Rev Neurol. 2024 Feb;20(2):84-98. doi: 10.1038/s41582-023-00916-w. Epub 2024 Jan 8. PMID: 38191918.
Myasthenia gravis (MG) is a rare neuromuscular disorder caused by an autoimmune response which blocks or damages acetylcholine receptors (AChRs) or muscle-specific kinase (MuSK) on muscles. To date, the standard therapy for MG has relied on acetylcholinesterase inhibitors, corticosteroids, and immunosuppressants. These therapies have shown good efficacy in improving MG-related symptoms in most individuals. However, they can also cause long-term adverse effects, and up to 15% of individuals with MG show limited or no response.
This review paper provides a comprehensive overview of emerging molecular therapies for MG. The author discusses progress in therapies associated with AChR antibodies and MuSK antibodies, including both challenges and opportunities.
The author notes that molecular therapies have the potential to revolutionize the MG treatment landscape, unlocking new potential for personalized medicine approaches.
Farina A, Villagrán-García M, Vogrig A, Zekeridou A, Muñiz-Castrillo S, Velasco R, Guidon AC, Joubert B, Honnorat J. Neurological adverse events of immune checkpoint inhibitors and the development of paraneoplastic neurological syndromes. Lancet Neurol. 2024 Jan;23(1):81-94. doi: 10.1016/S1474-4422(23)00369-1.
Bodansky A, Yu DJ, Rallistan A, Kalaycioglu M, Boonyaratanakornkit J, Green DJ, Gauthier J, Turtle CJ, Zorn K, O'Donovan B, Mandel-Brehm C, Asaki J, Kortbawi H, Kung AF, Rackaityte E, Wang CY, Saxena A, de Dios K, Masi G, Nowak RJ, O'Connor KC, Li H, Diaz VE, Casaletto KB, Gontrum EQ, Chan B, Kramer JH, Wilson MR, Utz PJ, Hill JA, Jackson SW, Anderson MS, DeRisi JL. Unveiling the autoreactome: Proteome-wide immunological fingerprints reveal the promise of plasma cell depleting therapy. medRxiv. 2023 Dec 20:2023.12.19.23300188. doi: 10.1101/2023.12.19.23300188.
Spagni G, Gastaldi M, Businaro P, Chemkhi Z, Carrozza C, Mascagna G, Falso S, Scaranzin S, Franciotta D, Evoli A, Damato V. Comparison of Fixed and Live Cell-Based Assay for the Detection of AChR and MuSK Antibodies in Myasthenia Gravis. Neurol Neuroimmunol Neuroinflamm. 2022 Oct 21;10(1):e200038. doi: 10.1212/NXI.0000000000200038. PMID: 36270951; PMCID: PMC9621337.
Myasthenia gravis (MG) is a neuromuscular disorder caused by an autoimmune response which blocks or damages acetylcholine receptors (AChRs) in muscles. Double seronegative myasthenia gravis (dSN-MG) is a type of MG where patients do not have detectable AChRs or muscle-specific tyrosine kinase (MuSK) antibodies, which are two of the most common antibody markers for MG. In some patients with dSN-MG, a technique called cell-based assay (CBA) can be used to detect these antibodies. However, research comparing fixed and live CBA is lacking.
In this study, the research group of MGNet Pilot Awardee Valentina Damato, MD, PhD, compared the performance of fixed and live CBAs in serum samples from 192 patients with radioimmunoassay (RIA)-dSN-MG and 100 control subjects. The team also assessed the sensitivity and specificity of these techniques in RIA-positive MG samples.
Results show that fixed CBA represents a valuable alternative to RIA for AChR and MuSK antibody detection in patients with MG. Authors note that fixed CBA could be considered as a first-step diagnostic test, while live CBA can be useful in serologic testing of RIA- and fixed CBA-negative samples.
Sikorski P, Li Y, Cheema M, Wolfe GI, Kusner LL, Aban I, Kaminski HJ. Serum metabolomics of treatment response in myasthenia gravis. PLoS One. 2023 Oct 10;18(10):e0287654. doi: 10.1371/journal.pone.0287654. PMID: 37816000; PMCID: PMC10564178
Myasthenia gravis (MG) is a neuromuscular disorder caused by an autoimmune response which blocks or damages acetylcholine receptors in muscles. The primary initial therapy for MG is high-dose prednisone use. However, more than a third of patients do not respond to this treatment. Currently, there are no biomarkers to predict clinical responsiveness to corticosteroid treatment.
In this study, researchers defined a treatment-responsive biomarker for MG patients undergoing corticosteroid therapy. The team used serum from MG patients collected for a clinical trial of thymectomy (removal of the thymus gland) and prednisone to create metabolomic and lipidomic profiles. Next, researchers correlated these profiles with treatment response.
Results show that metabolomic and lipidomic profiles could be used to predict treatment response. Authors note that variation in prednisone metabolism may determine how well patients respond to treatment.
Regnault A, Morel T, de la Loge C, Mazerolle F, Kaminski HJ, Habib AA. Measuring Overall Severity of Myasthenia Gravis (MG): Evidence for the Added Value of the MG Symptoms PRO. Neurol Ther. 2023 Oct;12(5):1573-1590. doi: 10.1007/s40120-023-00464-x. Epub 2023 May 11.
Schlatter MI, Yandamuri SS, O'Connor KC, Nowak RJ, Pham MC, Obaid AH, Redman C, Provost M, McSweeney PA, Pearlman ML, Tees MT, Bowen JD, Nash RA, Georges GE. Remission of severe myasthenia gravis after autologous stem cell transplantation. Ann Clin Transl Neurol. 2023 Sep 19. doi: 10.1002/acn3.51898. Epub ahead of print. PMID: 37726935
Myasthenia gravis (MG) is a rare neuromuscular disorder caused by an autoimmune response which blocks or damages acetylcholine receptors (AChRs) on muscles. High-dose chemotherapy (HDIT) and autologous hematopoietic cell transplantation (HCT), also known as bone marrow transplant, are potential treatments for MG.
In this study, researchers investigated the safety and efficacy of HDIT and HCT in a patient with severe, treatment-resistant MG. Results show that HDIT and HCT induced remission of MG. The team also assessed the effect of treatment on the underlying immunopathology. Intriguingly, the AChR autoantibodies—the known pathogenic mediators of MG—did not appreciably lower after the treatment.
Authors state that these findings suggest a cell-based disease mechanism, which responds to high-dose therapy, may play a role in the pathology in addition to AChR autoantibodies. Further studies are needed to establish whether HDIT and HCT can be an effective therapy for severe MG.
Lesport Q, Joerger G, Kaminski HJ, Girma H, McNett S, Abu-Rub M, Garbey M. Eye Segmentation Method for Telehealth: Application to the Myasthenia Gravis Physical Examination. Sensors (Basel). 2023 Sep 7;23(18):7744. doi: 10.3390/s23187744. PMID: 37765800; PMCID: PMC10536520
Myasthenia gravis (MG) is a neuromuscular disorder which produces muscle weakness that can worsen over the course of a minute during an examination. Use of telemedicine has recently increased for monitoring MG, although these evaluations rely entirely on subjective evaluations of an examiner.
In this study, researchers developed a new telehealth platform to assist with telemedicine evaluations of ocular manifestations of patients with MG. The team created a hybrid algorithm that combines deep learning with computer vision, giving quantitative metrics of ptosis (eyelid droop) and ocular muscle fatigue leading to symptoms like double vision.
The method, which works on both a fixed image and frame by frame of the video in real-time, is able to operate in standard telehealth conditions. Authors note that this approach is general and can be applied to many disorders of ocular motility and ptosis.
Oh S, Mao X, Manfredo-Vieira S, Lee J, Patel D, Choi EJ, Alvarado A, Cottman-Thomas E, Maseda D, Tsao PY, Ellebrecht CT, Khella SL, Richman DP, O'Connor KC, Herzberg U, Binder GK, Milone MC, Basu S, Payne AS. Precision targeting of autoantigen-specific B cells in muscle-specific tyrosine kinase myasthenia gravis with chimeric autoantibody receptor T cells. Nat Biotechnol. 2023 Sep;41(9):1229-1238. doi: 10.1038/s41587-022-01637-z. Epub 2023 Jan 19.
Pham MC, Masi G, Patzina R, Obaid AH, Oxendine SR, Oh S, Payne AS, Nowak RJ, O'Connor KC. Individual myasthenia gravis autoantibody clones can efficiently mediate multiple mechanisms of pathology. Acta Neuropathol. 2023 Aug;146(2):319-336. doi: 10.1007/s00401-023-02603-y. Epub 2023 Jun 21. PMID: 37344701
In patients with myasthenia gravis (MG), an autoimmune response blocks or damages acetylcholine receptors in muscles. Autoantibody clones drive three different pathogenic (disease-causing) mechanisms of MG, including complement activation, receptor blockade, and antigenic modulation. However, it is unclear whether these mechanisms are driven by single or multiple antibody clones.
In this study, researchers investigated the ability of individual autoantibody clones to drive multiple pathogenic mechanisms of MG. First, the team produced monoclonal autoantibodies (mAbs) from patients with MG. Next, researchers assessed the binding properties and pathogenic capacities of the mAbs.
Results show that these mAbs can drive pathology through blocking the acetylcholine binding site, internalizing the AChR through crosslinking (modulation), and activating complement. While some mAbs can drive one or two of these mechanisms, several mAbs were able to drive all three simultaneously. Authors note that these new insights on the immunopathology of MG could help inform therapeutic approaches.
Kusner LL, Misra RS, Lucas R. Editorial: Global excellence in inflammatory diseases: North America 2021. Front Immunol. 2023 Jul 6;14:1245827. doi: 10.3389/fimmu.2023.1245827. eCollection 2023.
Yandamuri SS, Filipek B, Obaid AH, Lele N, Thurman JM, Makhani N, Nowak RJ, Guo Y, Lucchinetti CF, Flanagan EP, Longbrake EE, O'Connor KC. MOGAD patient autoantibodies induce complement, phagocytosis, and cellular cytotoxicity. JCI Insight. 2023 Jun 8;8(11):e165373. doi: 10.1172/jci.insight.165373.
Masi G, Pham MC, Karatz T, Oh S, Payne AS, Nowak RJ, Howard JF Jr, Guptill JT, Juel VC, O'Connor KC. Clinicoserological insights into patients with immune checkpoint inhibitor-induced myasthenia gravis. Ann Clin Transl Neurol. 2023 May;10(5):825-831. doi: 10.1002/acn3.51761. Epub 2023 Mar 16.
Guptill JT, Benatar M, Granit V, Habib AA, Howard JF, Barnett-Tapia C, Nowak RJ, Lee I, Ruzhansky K, Dimachkie MM, Cutter GR, Kaminski HJ. Addressing Outcome Measure Variability in Myasthenia Gravis Clinical Trials. Neurology. 2023 Apr 19;10.1212/WNL.0000000000207278. doi: 10.1212/WNL.0000000000207278. Online ahead of print.
Damato V, Spagni G, Monte G, Scandiffio L, Cavalcante P, Zampetti N, Fossati M, Falso S, Mantegazza R, Battaglia A, Fattorossi A, Evoli A. Immunological response after SARS-CoV-2 infection and mRNA vaccines in patients with myasthenia gravis treated with Rituximab. Neuromuscul Disord. 2023 Mar;33(3):288-294. doi: 10.1016/j.nmd.2023.02.005. Epub 2023 Feb 11.
Garbey M, Joerger G, Lesport Q, Girma H, McNett S, Abu-Rub M, Kaminski H. A Digital Telehealth System to Compute Myasthenia Gravis Core Examination Metrics: Exploratory Cohort Study. JMIR Neurotech. 2023;2:e43387. doi: 10.2196/43387. Epub 2023 Apr 19. PMID: 37435094; PMCID: PMC10334459
Myasthenia gravis (MG) is a neuromuscular disorder caused by an autoimmune response which blocks or damages acetylcholine receptors in muscles. Recently, telemedicine practices have grown for neurological diseases, including MG. Telemedicine evaluation of patients with MG has been recommended via the Myasthenia Gravis Core Examination (MG-CE).
In this study, researchers developed a new telehealth system to automate data acquisition and analytics during the MG-CE. Using Zoom videos of patients with MG undergoing the MG-CE, the team created an algorithm toolbox—including computer vision and signal processing methods—to analyze eye motions, body motions, and vocalizations.
Results show that this new system can objectively quantitate metrics from the MG-CE, allowing the medical examiner to concentrate on the patient instead of managing logistics. Authors note that the system could also be applied to many other neurological disorders, potentially improving clinical care.
Benatar M, Cutter G, Kaminski HJ. The best and worst of times in therapy development for myasthenia gravis. Muscle Nerve. 2022 Nov 2. doi: 10.1002/mus.27742. Epub ahead of print. PMID: 36321730.
Fichtner ML, Hoehn KB, Ford EE, Mane-Damas M, Oh S, Waters P, Payne AS, Smith ML, Watson CT, Losen M, Martinez-Martinez P, Nowak RJ, Kleinstein SH, O'Connor KC. Reemergence of pathogenic, autoantibody-producing B cell clones in myasthenia gravis following B cell depletion therapy. Acta Neuropathol Commun. 2022 Oct 28;10(1):154. doi: 10.1186/s40478-022-01454-0. PMID: 36307868; PMCID: PMC9617453.
Damato V, Spagni G, Monte G, Woodhall M, Jacobson L, Falso S, Smith T, Iorio R, Waters P, Irani SR, Vincent A, Evoli A. Clinical value of cell-based assays in the characterisation of seronegative myasthenia gravis. J Neurol Neurosurg Psychiatry. 2022 Sep;93(9):995-1000. doi: 10.1136/jnnp-2022-329284. Epub 2022 Jul 14.
Masi G, O'Connor KC. Novel pathophysiological insights in autoimmune myasthenia gravis. Curr Opin Neurol. 2022 Aug 5. doi: 10.1097/WCO.0000000000001088. Epub ahead of print. PMID: 35942663.
Myasthenia gravis (MG) is a neuromuscular disorder caused by an autoimmune response which blocks or damages acetylcholine receptors in muscles. Affected receptors cannot properly receive nerve signals, impacting voluntary muscle contractions. Generalized muscle weakness and fatigue with prolonged activity are characteristic symptoms, which improve with rest. In this review article, authors summarize recent insights into the development of MG relating to the immune system, including the mechanisms of various MG disease subtypes. They also describe the wide range of treatment options now available to patients with MG, which have uncovered significant differences in clinical responses between subtypes. These differences could help clinicians choose specific therapeutic strategies. Authors conclude that improved understanding of autoantibodies is revealing the mechanisms that guide the development of MG. In the future, authors note that studies on the differences in immunology among MG patients will be key to developing effective, individualized therapies.
Masi G, Li Y, Karatz T, Pham MC, Oxendine SR, Nowak RJ, Guptill JT, O'Connor KC. The clinical need for clustered AChR cell-based assay testing of seronegative MG. J Neuroimmunol. 2022 Jun 15;367:577850. doi: 10.1016/j.jneuroim.2022.577850. Epub 2022 Mar 25.
Guidon AC, Guptill JT, Aban I, Cutter G, Soliven B, Benatar M, Kaminski HJ, Nowak RJ, on behalf of MGNet. Adapting Disease Specific Outcome Measures Pilot Trial for Telehealth in Myasthenia Gravis (ADAPT-teleMG): An Innovation in Rare Disesae Study Design During the COVID-19 Pandemic. Muscle Nerve. 2022 May. [Presented as poster at the 14th MGFA International Conference on Myasthenia and Related Disorders in Miami, Florida in May 2022, Presented at the EveryLife Foundation for Rare Diseases 2020 Scientific Workshop.]
Guptill JT, Nowak RJ, Guidon AC, Howard JF, Soliven B, Hammett A, Munro Sheldon B, Li Y, Meece T, Aban I, Cutter G, Kaminski HJ, and the EXPLORE-MG2 Study Team. A prospective natural history study and biorepository for patients with myasthenia gravis (EXPLORE-MG2). Muscle Nerve. 2022 May; 65:S1;S7-S8. [Presented as poster at the 14th MGFA International Conference on Myasthenia and Related Disorders in Miami, Florida in May 2022.]
Obaid AH, Zografou C, Vadysirisack DD, Munro-Sheldon B, Fichtner ML, Roy B, Philbrick WM, Bennett JL, Nowak RJ, O'Connor KC. Heterogeneity of Acetylcholine Receptor Autoantibody-Mediated Complement Activity in Patients With Myasthenia Gravis. Neurol Neuroimmunol Neuroinflamm.. 2022 Apr 26;9(4):e1169. doi: 10.1212/NXI.0000000000001169. PMID: 35473886.
Myasthenia gravis (MG) is a neuromuscular disorder caused by an autoimmune response which blocks or damages acetylcholine receptors in muscles. Clinical assays—laboratory tests used to diagnose and monitor patients—only measure autoantibody binding. Therefore, these tests often provide limited insight on disease burden and therapeutic response. To address these limitations, Dr. Kevin C. O’Connor and colleagues at Yale University developed a new assay for evaluating acetylcholine receptor autoantibody–mediated complement activity. Results suggested that a subset of patients lacks association between membrane attack complex formation and autoantibody binding or disease burden. Authors note that this assay provides a better understanding of autoantibody mechanisms and may improve predictions for treatment response. Ultimately, these measurements could help assess disease progression and provide more individualized treatment plans.
Kaminski HJ, Denk J. Corticosteroid Treatment-Resistance in Myasthenia Gravis. Front Neurol. 2022 Apr 25;13:886625. doi: 10.3389/fneur.2022.886625. eCollection 2022.
Guptill JT, Nowak RJ, Guidon AC, Howard JF, Soliven B, Hammett A, Munro Sheldon B, Li Y, Meece T, Aban I, Cutter G, Kaminski HJ, and the EXPLORE-MG2 Study Team. A prospective natural history study and biorepository for patients with myasthenia gravis (EXPLORE-MG2). Neurology. 2022 April P.6005. [Presented as poster at the 2022 American Academy of Neurology (AAN) Annual Meeting in Seattle, WA April 2022.]
Fichtner ML, Hoarty MD, Vadysirisack DD, Munro-Sheldon B, Nowak RJ, O'Connor KC. Myasthenia gravis complement activity is independent of autoantibody titer and disease severity. PLoS One. 2022 Mar 15;17(3):e0264489. doi: 10.1371/journal.pone.0264489. eCollection 2022.
Chia R, Saez-Atienzar S, Murphy N, Chiò A, Blauwendraat C; International Myasthenia Gravis Genomics Consortium, Roda RH, Tienari PJ, Kaminski HJ, Ricciardi R, Guida M, De Rosa A, Petrucci L, Evoli A, Provenzano C, Drachman DB, Traynor BJ. Identification of genetic risk loci and prioritization of genes and pathways for myasthenia gravis: a genome-wide association study. Proc Natl Acad Sci U S A. 2022 Feb 1;119(5):e2108672119. doi: 10.1073/pnas.2108672119.
Verschuuren JJ, Palace J, Murai H, Tannemaat MR, Kaminski HJ, Bril V. Advances and ongoing research in the treatment of autoimmune neuromuscular junction disorders. Erratum in: Lancet Neurol. 2022 Feb;21(2):189-202. doi: 10.1016/S1474-4422(21)00463-4. Erratum in: Lancet Neurol. 2022 Mar;21(3):e3. PMID: 35065041.
Cleanthous S, Mork AC, Regnault A, Cano S, Kaminski HJ, Morel T. Development of the Myasthenia Gravis (MG) Symptoms PRO: a case study of a patient-centred outcome measure in rare disease. Orphanet J Rare Dis. 2021 Oct 30;16(1):457. doi: 10.1186/s13023-021-02064-0.
Mandel-Brehm C, Fichtner ML, Jiang R, Winton VJ, Vazquez SE, Pham MC, Hoehn KB, Kelleher NL, Nowak RJ, Kleinstein SH, Wilson MR, DeRisi JL, O'Connor KC. Elevated N-Linked Glycosylation of IgG V Regions in Myasthenia Gravis Disease Subtypes. J Immunol. 2021 Oct 15;207(8):2005-2014. doi: 10.4049/jimmunol.2100225. Epub 2021 Sep 20.
Guidon AC, Muppidi S, Nowak RJ, Guptill JT, Hehir MK, Ruzhansky K, Burton LB, Post D, Cutter G, Conwit R, Mejia NI, Kaminski HJ, Howard JF Jr. Telemedicine visits in myasthenia gravis: Expert guidance and the Myasthenia Gravis Core Exam (MG-CE). Muscle Nerve. 2021 Sep;64(3):270-276. doi: 10.1002/mus.27260. Epub 2021 Jul 7.
Fichtner ML, Vieni C, Redler RL, Kolich L, Jiang R, Takata K, Stathopoulos P, Suarez PA, Nowak RJ, Burden SJ, Ekiert DC, O'Connor KC. Affinity maturation is required for pathogenic monovalent IgG4 autoantibody development in myasthenia gravis. J Exp Med. 2020 Dec 7;217(12):e20200513. doi: 10.1084/jem.20200513.
Alabbad S, AlGaeed M, Sikorski P, Kaminski HJ. Monoclonal Antibody-Based Therapies for Myasthenia Gravis. BioDrugs. 2020 Oct;34(5):557-566. doi: 10.1007/s40259-020-00443-w.
Green JD, Barohn RJ, Bartoccion E, Benatar M, Blackmore D, Chaudhry V, Chopra M, Corse A, Dimachkie MM, Evoli A, Florence J, Freimer M, Howard JF, Jiwa T, Kaminski HJ, Kissel JT, Koopman WJ, Lipscomb B, Maestri M, Marino M, Massey JM, McVey A, Mezei MM, Muppidi S, Nicolle MW, Oger J, Pascuzzi RM, Pasnoor M, Pestronk A, Provenzano C, Ricciardi R, Richman DP, Rowin J, Sanders DB, Siddiqi Z, Soloway A, Wolfe GI, Wulf C, Drachman DB, Traynor BJ. Epidemiological evidence for a hereditary contribution to myasthenia gravis: a retrospective cohort study of patients from North America. BMJ Open. 2020 Sep 18;10(9):e037909. doi: 10.1136/bmjopen-2020-037909.
Jiang R, Fichtner ML, Hoehn KB, Pham MC, Stathopoulos P, Nowak RJ, Kleinstein SH, O'Connor KC. Single-cell repertoire tracing identifies rituximab refractory B cells during myasthenia gravis relapses. JCI Insight. 2020 Jul 23;5(14):e136471. doi: 10.1172/jci.insight.136471. PMID: 32573488; PMCID: PMC7453893.
Albazli K, Kaminski HJ, Howard JF Jr. Complement Inhibitor Therapy for Myasthenia Gravis. Front Immunol. 2020 Jun 3;11:917. doi: 10.3389/fimmu.2020.00917. eCollection 2020.
Fichtner ML, Jiang R, Bourke A, Nowak RJ, O'Connor KC. Autoimmune Pathology in Myasthenia Gravis Disease Subtypes Is Governed by Divergent Mechanisms of Immunopathology. Front Immunol. 2020 May 27;11:776. doi: 10.3389/fimmu.2020.00776. eCollection 2020.
Meffre E, O'Connor KC. Impaired B-cell tolerance checkpoints promote the development of autoimmune diseases and pathogenic autoantibodies. Immunol Rev. 2019 Nov;292(1):90-101. doi: 10.1111/imr.12821. Epub 2019 Nov 12.
Roy B, Chen J, Khani-Habibabadi F, McLaren N, Soliven BC, Juel VC, O'Connor KC, Nowak RJ, Kusner LL, Kaminski HJ. A Distinct Immunological Signature in Late-Onset Myasthenia Gravis: Insights from an Exploratory Proteomics Study. Ann Neurol. 2025 Sep 6. doi: 10.1002/ana.78017. Epub ahead of print. PMID: 40913424.
Myasthenia gravis (MG) is a neuromuscular disorder caused by an autoimmune response which blocks or damages acetylcholine receptors in muscles, causing disabling weakness. Patients with early-onset MG develop symptoms before age 50, while patients with late-onset MG develop symptoms after age 50. Not much is known about how early-onset and late-onset MG affect the body differently.
Utilizing sera (the liquid part of blood that remains after coagulation) from the NIH-sponsored BeatMG clinical trial and MGNet, researchers performed proteomics analysis of 768 inflammatory proteins and uncovered a distinct immunological signature that differentiates late-onset from early-onset myasthenia gravis.
Pathways linked to leukocyte differentiation and myeloid cell migration were enriched in late-onset disease. Seven proteins were further replicated in the UK Biobank, and IL18R1, CXCL17, and CCL11 were validated in an independent cohort that were specific to late-onset MG. Investigators note that further studies are needed to confirm the use of these proteins as biomarkers of late-onset MG, as well as their use for improving therapeutic precision and patient outcomes.
Fernández AC, Estrella J, Oglesbee D, Larson AA, Van Hove JLK. The clinical utility in hospital-wide use of growth differentiation factor 15 as a biomarker for mitochondrial DNA-related disorders. J Inherit Metab Dis. 2024 Nov 24. doi: 10.1002/jimd.12821. Epub ahead of print. PMID: 39582258.
Primary mitochondrial disorders (PMD) are chronic, multisystemic disorders involving dysfunction of the mitochondria caused by mutations in the mitochondrial DNA (mtDNA) or nuclear DNA (nDNA). Due to the clinical and genetic diversity of PMD, recognition of these disorders in a clinical setting is often difficult.
In this study, researchers explored the clinical utility of growth differentiation factor 15 (GDF15) as a biomarker for PMD. First, the team reviewed medical records from 418 cases where GDF15 levels were obtained by clinicians at a tertiary care hospital. Next, they classified each case as PMD due to mtDNA-related defects (mtDNA deletions, mtDNA depletion, tRNA variants), PMD due to structural defects or other nuclear causes, and non-mitochondrial disease. Patients with liver disease or systemic critical illness were excluded. Finally, GDF15 was assayed in a clinical laboratory.
Results show that in a real-life clinical setting—after excluding abnormal liver function and critical illness—GDF15 had good clinical utility of increasing the odds at predicting mtDNA-related primary mitochondrial disorders by 14-fold. An elevated GDF15 had 40.8% odds of identifying an mtDNA-related mitochondrial disorder versus 2.7% if not elevated. However, GDF15 did not show good clinical utility as a biomarker for structural or other nuclear-encoded primary mitochondrial disorders.
Grady LO, Zoltick ES, Zouk H, He W, Perez E, Clarke L, Gold J, Strong A, Sahai I, Yeo J, Green RC, Karaa A, Gold NB. Long-Term Health Outcomes of Individuals With Pseudodeficiency Alleles in IDUA May Inform Newborn Screening Practices for Mucopolysaccharidosis Type I. Am J Med Genet A. 2024 Nov 19:e63940. doi: 10.1002/ajmg.a.63940. Epub ahead of print. PMID: 39559959.
Starosta RT, Larson AA, Meeks NJL, Gracie S, Friederich MW, Gaughan SM, Baker PR 2nd, Knupp KG, Michel CR, Reisdorph R, Hock DH, Stroud DA, Wood T, Van Hove JLK. An integrated multi-omics approach allowed ultra-rapid diagnosis of a deep intronic pathogenic variant in PDHX and precision treatment in a neonate critically ill with lactic acidosis. Mitochondrion. 2024 Oct 15;79:101973. doi: 10.1016/j.mito.2024.101973. Epub ahead of print. PMID: 39413893.
Pyruvate dehydrogenase complex (PDH) deficiency is a mitochondrial disease that limits the breakdown of carbohydrates for energy production, leading to high levels of lactic acid, which can be life-threatening. Diagnosing mitochondrial diseases like PDH is often complex, with limited options for additional tests after a negative rapid whole-genome sequencing result.
In this study, researchers used a proteomics-based approach for ultra-rapid diagnosis of PDH deficiency. The study included a neonatal patient presenting with severe lactic acidosis on the second day of life and a negative initial ultra-rapid genome sequencing report. With multi-omics techniques, the team identified PDHX from absence of peptides in the cells, leading to the discovery of a pathogenic variant in the PDHX gene. Subsequent testing in the following months confirmed a diagnosis of PDH deficiency, and the patient was successfully treated for lactic acidosis with dichloroacetate.
Results highlight the power of rapid proteomics in guiding genomic analysis. Authors also note that these results identify dichloroacetate as a promising potential therapy for lactic acidosis in PDH deficiency.
Hidalgo-Gutierrez A, Shintaku J, Ramon J, Barriocanal-Casado E, Pesini A, Saneto RP, Garrabou G, Milisenda JC, Matas-Garcia A, Gort L, Ugarteburu O, Gu Y, Koganti L, Wang T, Tadesse S, Meneri M, Sciacco M, Wang S, Tanji K, Horwitz MS, Dorschner MO, Mansukhani M, Comi GP, Ronchi D, Marti R, Ribes A, Tort F, Hirano M. Guanylate Kinase 1 Deficiency: A Novel and Potentially Treatable Mitochondrial DNA Depletion/Deletions Disease. Ann Neurol. 2024 Sep 4. doi: 10.1002/ana.27071. Epub ahead of print. PMID: 39230499.
Mitochondrial DNA depletion/deletions syndrome (MDDS) is a group of disorders in which copies of the DNA within mitochondria (specialized cell structures that produce energy) are severely reduced in number. MDDS results in impaired energy production required for proper functioning of the body tissues and organs, affecting the brain, liver, digestive system, nerves, and skeletal muscles.
In this study, researchers identified a new and potentially treatable cause of MDDS. The team performed whole exome sequencing to investigate pathogenic variants in four patients who presented with MDDS symptoms, but did not have a known genetic cause.
Results revealed pathogenic variants in the GUK1 gene in all four patients and that the GUK1 protein has a long mitochondrial isoform and a short cytosolic isoform. The team also identified effective in vitro therapeutic strategies to restore mitochondrial DNA levels, highlighting potential treatments for this disorder. Authors note that GUK1 deficiency is the first example of impaired nucleotide monophosphate kinase causing MDDS.
Nakai R, Varnum S, Field RL, Shi H, Giwa R, Jia W, Krysa SJ, Cohen EF, Borcherding N, Saneto RP, Tsai RC, Suganuma M, Ohta H, Yokota T, Brestoff JR. Mitochondria transfer-based therapies reduce the morbidity and mortality of Leigh syndrome. Nat Metab. 2024 Sep 2. doi: 10.1038/s42255-024-01125-5. Online ahead of print.
Van Hove JLK, Friederich MW, Hock DH, Stroud DA, Caruana NJ, Christians U, Schniedewind B, Michel CR, Reisdorph R, Lopez Gonzalez EDJ, Brenner C, Donovan TE, Lee JC, Chatfield KC, Larson AA, Baker PR 2nd, McCandless SE, Moore Burk MF. ACAD9 treatment with bezafibrate and nicotinamide riboside temporarily stabilizes cardiomyopathy and lactic acidosis. Mitochondrion. 2024 Sep;78:101905. doi: 10.1016/j.mito.2024.101905. Epub 2024 May 24.
Komulainen-Ebrahim J, Kangas SM, López-Martín E, Feyma T, Scaglia F, Martínez-Delgado B, Kuismin O, Suo-Palosaari M, Carr L, Hinttala R, Kurian MA, Uusimaa J. Hyperkinetic Movement Disorder Caused by the Recurrent c.892C>T NACC1 Variant. Mov Disord Clin Pract. 2024 Jun;11(6):708-715. doi: 10.1002/mdc3.14051. Epub 2024 May 2.
Kelly C, Junker A, Englestad K, Hirano M, Trumpff C, Picard M. Perceived association of mood and symptom severity in adults with mitochondrial diseases. medRxiv. 2024 Feb 4:2024.02.02.24302076. doi: 10.1101/2024.02.02.24302076.
Verma A, Lehman AN, Gokcan H, Cropcho L, Black D, Dobrowolski SF, Vockley J, Bedoyan JK. Amino acid ratio combinations as biomarkers for discriminating patients with pyruvate dehydrogenase complex deficiency from other inborn errors of metabolism. Mol Genet Genomic Med. 2023 Sep 8:e2283. doi: 10.1002/mgg3.2283. Epub ahead of print. PMID: 37688338.
Solis EM, Good LB, Vázquez RG, Patnaik S, Hernandez-Reynoso AG, Ma Q, Angulo G, Dobariya A, Cogan SF, Pancrazio JJ, Pascual JM, Jakkamsetti V. Isolation of the murine Glut1 deficient thalamocortical circuit: wavelet characterization and reverse glucose dependence of low and gamma frequency oscillations. bioRxiv. 2023 Aug 20:2023.06.05.543611. doi: 10.1101/2023.06.05.543611. Preprint.
Karaa A, Bertini E, Carelli V, Cohen BH, Enns GM, Falk MJ, Goldstein A, Gorman GS, Haas R, Hirano M, Klopstock T, Koenig MK, Kornblum C, Lamperti C, Lehman A, Longo N, Molnar MJ, Parikh S, Phan H, Pitceathly RDS, Saneto R, Scaglia F, Servidei S, Tarnopolsky M, Toscano A, Van Hove JLK, Vissing J, Vockley J, Finman JS, Brown DA, Shiffer JA, Mancuso M; MMPOWER-3 Trial Investigators. Efficacy and Safety of Elamipretide in Individuals With Primary Mitochondrial Myopathy: The MMPOWER-3 Randomized Clinical Trial. Neurology. 2023 Jul 18;101(3):e238-e252. doi: 10.1212/WNL.0000000000207402. Epub 2023 Jun 2.
Lareau CA, Dubois SM, Buquicchio FA, Hsieh YH, Garg K, Kautz P, Nitsch L, Praktiknjo SD, Maschmeyer P, Verboon JM, Gutierrez JC, Yin Y, Fiskin E, Luo W, Mimitou EP, Muus C, Malhotra R, Parikh S, Fleming MD, Oevermann L, Schulte J, Eckert C, Kundaje A, Smibert P, Vardhana SA, Satpathy AT, Regev A, Sankaran VG, Agarwal S, Ludwig LS. Single-cell multi-omics of mitochondrial DNA disorders reveals dynamics of purifying selection across human immune cells. Nat Genet. 2023 Jul;55(7):1198-1209. doi: 10.1038/s41588-023-01433-8. Epub 2023 Jun 29. PMID: 37386249
Mitochondrial diseases are multisystemic, genetic disorders involving dysfunction of the mitochondria (specialized cell structures that produce energy), which affects cellular metabolism. Diverse mitochondrial DNA (mtDNA) mutations are associated with diverse phenotypes (observable characteristics), suggesting that metabolic vulnerabilities may be specific to organ and cell types.
In this study, researchers developed a multi-omics approach to investigate the properties of mitochondrial genetics. In single cells derived from six patients with mitochondrial diseases, the team quantified deletions in mtDNA alongside cell state features.
Results reveal the dynamics of pathogenic (disease-causing) mtDNA heteroplasmy (multiple variants within a cell) in individual blood and immune cells. Authors note that these findings demonstrate the power of single-cell multi-omics to reveal fundamental properties of mitochondrial genetics.
Thompson JLP, Karaa A, Pham H, Yeske P, Krischer J, Xiao Y, Long Y, Kramer A, Dimmock D, Holbert A, Gorski C, Engelstad KM, Buchsbaum R, Rosales XQ, Hirano M. The evolution of the mitochondrial disease diagnostic odyssey. Orphanet J Rare Dis. 2023 Jun 22;18(1):157. doi: 10.1186/s13023-023-02754-x.
Duque Lasio LM, Leshinski AC, Ducich NH, Flore LA, Lehman A, Shur N, Jayakar PB, Hainline BE, Basinger AA, Wilson WG, Diaz GA, Erbe RW, Koeberl DD, Vockley J, Bedoyan JK. Clinical, biochemical and molecular characterization of 12 patients with pyruvate carboxylase deficiency treated with triheptanoin. Mol Genet Metab. 2023 Jun;139(2):107605. doi: 10.1016/j.ymgme.2023.107605. Epub 2023 May 9. PMID: 37207470; PMCID: PMC10330474.
Vogel GF, Mozer-Glassberg Y, Landau YE, Schlieben LD, Prokisch H, Feichtinger RG, Mayr JA, Brennenstuhl H, Schröter J, Pechlaner A, Alkuraya FS, Baker JJ, Barcia G, Baric I, Braverman N, Burnyte B, Christodoulou J, Ciara E, Coman D, Das AM, Darin N, Della Marina A, Distelmaier F, Eklund EA, Ersoy M, Fang W, Gaignard P, Ganetzky RD, Gonzales E, Howard C, Hughes J, Konstantopoulou V, Kose M, Kerr M, Khan A, Lenz D, McFarland R, Margolis MG, Morrison K, Müller T, Murayama K, Nicastro E, Pennisi A, Peters H, Piekutowska-Abramczuk D, Rötig A, Santer R, Scaglia F, Schiff M, Shagrani M, Sharrard M, Soler-Alfonso C, Staufner C, Storey I, Stormon M, Taylor RW, Thorburn DR, Teles EL, Wang JS, Weghuber D, Wortmann S. Genotypic and phenotypic spectrum of infantile liver failure due to pathogenic TRMU variants. Genet Med. 2023 Jun;25(6):100314. doi: 10.1016/j.gim.2022.09.015. Epub 2022 Oct 29.
Hirano M, Pitceathly RDS. Progressive external ophthalmoplegia. Handb Clin Neurol. 2023;194:9-21. doi: 10.1016/B978-0-12-821751-1.00018-X.
Ju Wang JD, Chen M, Zhang C, Parker J, Saneto R, Ramirez JM. Sleep and Breathing Disturbances in Children With Leigh Syndrome: A Comparative Study. Pediatr Neurol. 2022 Nov;136:56-63. doi: 10.1016/j.pediatrneurol.2022.08.006. Epub 2022 Aug 29.
Almannai M, El-Hattab AW, Azamian MS, Ali M, Scaglia F. Mitochondrial DNA maintenance defects: potential therapeutic strategies. Mol Genet Metab. 2022 Sep-Oct;137(1-2):40-48. doi: 10.1016/j.ymgme.2022.07.003. Epub 2022 Jul 6. PMID: 35914366.
Mitochondrial DNA maintenance defects (MDMDs) are a group of disorders characterized by mitochondrial DNA (mtDNA) depletions and/or multiple deletions. These disorders most often affect the brain, liver, skeletal muscle, peripheral nerves, and gastrointestinal tract. As with other mitochondrial disorders, treatment options for MDMDs are currently limited. Recent progress in MDMD research includes the development of model organisms, improved understanding of their pathophysiology, and a better knowledge of their natural history. This progress has led to an increasing number of preclinical studies, as well as existing and planned clinical trials. In this review paper, researchers discuss current studies and trials, including potential new therapeutic options for MDMDs.
Gokcan H, Bedoyan JK, Isayev O. Simulations of Pathogenic E1α Variants: Allostery and Impact on Pyruvate Dehydrogenase Complex-E1 Structure and Function. J Chem Inf Model. 2022 Jul 25;62(14):3463-3475. doi: 10.1021/acs.jcim.2c00630. Epub 2022 Jul 7.
Pernice WM, Eyaid W, Gc JB, Brown ZP, Juanola-Falgarona M, Torres-Torronteras J, Sommerville EW, Hellebrekers DM, Blakely EL, Donaldson A, van de Laar I, Leu CS, Marti R, Frank J, Tanji K, Koolen DA, Rodenburg RJ, Chinnery PF, Smeets HJM, Gorman GS, Bonnen PE, Taylor RW, Hirano M. RRM1 variants cause a mitochondrial DNA maintenance disorder via impaired de novo nucleotide synthesis. J Clin Invest.. 2022 Jul 1;132(13):e145660. doi: 10.1172/JCI145660. PMID: 35617047; PMCID: PMC9246377.
Emmanuele V, Ganesh J, Vladutiu G, Haas R, Kerr D, Saneto RP, Cohen BH, Van Hove JLK, Scaglia F, Hoppel C, Rosales XQ, Barca E, Buchsbaum R, Thompson JL, DiMauro S, Hirano M; North American Mitochondrial Disease Consortium (NAMDC). Time to harmonize mitochondrial syndrome nomenclature and classification: A consensus from the North American Mitochondrial Disease Consortium (NAMDC). Mol Genet Metab. 2022 Jun;136(2):125-131. doi: 10.1016/j.ymgme.2022.05.001. Epub 2022 May 13.
Ganapathi M, Friocourt G, Gueguen N, Friederich MW, Le Gac G, Okur V, Loaëc N, Ludwig T, Ka C, Tanji K, Marcorelles P, Theodorou E, Lignelli-Dipple A, Voisset C, Walker MA, Briere LC, Bourhis A, Blondel M, LeDuc C, Hagen J, Cooper C, Muraresku C, Ferec C, Garenne A, Lelez-Soquet S, Rogers CA, Shen Y, Strode DK, Bizargity P, Iglesias A, Goldstein A, High FA, Network UD, Sweetser DA, Ganetzky R, Van Hove JLK, Procaccio V, Le Marechal C, Chung WK. A homozygous splice variant in ATP5PO, disrupts mitochondrial complex V function and causes Leigh syndrome in two unrelated families. J Inherit Metab Dis. 2022 May 27. doi: 10.1002/jimd.12526. Online ahead of print.
Karaa A, MacMullen LE, Campbell JC, Christodoulou J, Cohen BH, Klopstock T, Koga Y, Lamperti C, van Maanen R, McFarland R, Parikh S, Rahman S, Scaglia F, Sherman AV, Yeske P, Falk MJ. Community Consensus Guidelines to Support FAIR Data Standards in Clinical Research Studies in Primary Mitochondrial Disease. Adv Genet (Hoboken). 2022 Mar;3(1):2100047. doi: 10.1002/ggn2.202100047. Epub 2021 Dec 19.
Yang JH, Friederich MW, Ellsworth KA, Frederick A, Foreman E, Malicki D, Dimmock D, Lenberg J, Prasad C, Yu AC, Anthony Rupar C, Hegele RA, Manickam K, Koboldt DC, Crist E, Choi SS, Farhan SMK, Harvey H, Sattar S, Karp N, Wong T, Haas R, Van Hove JLK, Wigby K. Expanding the phenotypic and molecular spectrum of NFS1-related disorders that cause functional deficiencies in mitochondrial and cytosolic iron-sulfur cluster containing enzymes. Hum Mutat. 2022 Mar;43(3):305-315. doi: 10.1002/humu.24330. Epub 2022 Jan 19.
Carelli V, Hirano M, Enríquez JA, Chinnery PF. Implications of mitochondrial DNA mutations in human induced pluripotent stem cells. Nat Rev Genet. 2022 Feb;23(2):69-70. doi: 10.1038/s41576-021-00430-z.
Ducich NH, Mears JA, Bedoyan JK. Solvent accessibility of E1α and E1β residues with known missense mutations causing pyruvate dehydrogenase complex (PDC) deficiency: Impact on PDC-E1 structure and function. J Inherit Metab Dis. 2022 Jan 17. doi: 10.1002/jimd.12477. Online ahead of print.
Berardo A, Domínguez-González C, Engelstad K, Hirano M. Advances in Thymidine Kinase 2 Deficiency: Clinical Aspects, Translational Progress, and Emerging Therapies. J Neuromuscul Dis. 2022;9(2):225-235. doi: 10.3233/JND-210786.
Lopez-Gomez C, Sanchez-Quintero MJ, Lee EJ, Kleiner G, Tadesse S, Xie J, Akman HO, Gao G, Hirano M. Synergistic Deoxynucleoside and Gene Therapies for Thymidine Kinase 2 Deficiency. Ann Neurol. 2021 Oct;90(4):640-652. doi: 10.1002/ana.26185. Epub 2021 Aug 13.
Friederich MW, Geddes GC, Wortmann SB, Punnoose A, Wartchow E, Knight KM, Prokisch H, Creadon-Swindell G, Mayr JA, Van Hove JLK. Pathogenic variants in MRPL44 cause infantile cardiomyopathy due to a mitochondrial translation defect. Mol Genet Metab. 2021 Aug;133(4):362-371. doi: 10.1016/j.ymgme.2021.06.001. Epub 2021 Jun 10.
Saneto RP, Patrick KE, Perez FA. Homoplasmy of the m. 8993 T>G variant in a patient without MRI findings of Leigh syndrome, ataxia or retinal abnormalities. Mitochondrion. 2021 Jul;59:58-62. doi: 10.1016/j.mito.2021.04.010. Epub 2021 Apr 22.
Zolkipli-Cunningham Z, Naviaux JC, Nakayama T, Hirsch CM, Monk JM, Li K, Wang L, Le TP, Meinardi S, Blake DR, Naviaux RK. Metabolic and behavioral features of acute hyperpurinergia and the maternal immune activation mouse model of autism spectrum disorder. PLoS One. 2021 Mar 18;16(3):e0248771. doi: 10.1371/journal.pone.0248771. eCollection 2021.
Hirano M, Carelli V, De Giorgio R, Pironi L, Accarino A, Cenacchi G, D'Alessandro R, Filosto M, Martí R, Nonino F, Pinna AD, Baldin E, Bax BE, Bolletta A, Bolletta R, Boschetti E, Cescon M, D'Angelo R, Dotti MT, Giordano C, Gramegna LL, Levene M, Lodi R, Mandel H, Morelli MC, Musumeci O, Pugliese A, Scarpelli M, Siniscalchi A, Spinazzola A, Tal G, Torres-Torronteras J, Vignatelli L, Zaidman I, Zoller H, Rinaldi R, Zeviani M. Mitochondrial neurogastrointestinal encephalomyopathy (MNGIE): Position paper on diagnosis, prognosis, and treatment by the MNGIE International Network. J Inherit Metab Dis. 2021 Mar;44(2):376-387. doi: 10.1002/jimd.12300. Epub 2020 Sep 8.
Sen K, Grahame G, Bedoyan JK, Gropman AL. Novel presentations associated with a PDHA1 variant – Alternating hemiplegia in hemizygote proband and Guillain Barre Syndrome in heterozygote mother. Eur J Paediatr Neurol. 2021 Mar;31:27-30.
Hirano M, Berardo A, Barca E, Emmanuele V, Quinzii C, Simpson CV, Engelstad K, Rosales XQ, Thompson JLP. Regulatory environment for novel therapeutic development in mitochondrial diseases. J Inherit Metab Dis. 2021 Mar;44(2):292-300. doi: 10.1002/jimd.12353. Epub 2021 Jan 4.
Murali CN, Soler-Alfonso C, Loomes KM, Shah AA, Monteil D, Padilla CD, Scaglia F, Ganetzky R. TRMU deficiency: A broad clinical spectrum responsive to cysteine supplementation. Mol Genet Metab. 2021 Feb;132(2):146-153. doi: 10.1016/j.ymgme.2021.01.005. Epub 2021 Jan 14.
Kripps KA, Friederich MW, Chen T, Larson AA, Mirsky DM, Wang Y, Tanji K, Knight KM, Wong LJ, Van Hove JLK. A novel acceptor stem variant in mitochondrial tRNA(Tyr) impairs mitochondrial translation and is associated with a severe phenotype. Mol Genet Metab. 2020 Dec;131(4):398-404. doi: 10.1016/j.ymgme.2020.11.006. Epub 2020 Nov 24.
McCormick EM, Lott MT, Dulik MC, Shen L, Attimonelli M, Vitale O, Karaa A, Bai R, Pineda-Alvarez DE, Singh LN, Stanley CM, Wong S, Bhardwaj A, Merkurjev D, Mao R, Sondheimer N, Zhang S, Procaccio V, Wallace DC, Gai X, Falk MJ. Specifications of the ACMG/AMP standards and guidelines for mitochondrial DNA variant interpretation. Hum Mutat. 2020 Dec;41(12):2028-2057. doi: 10.1002/humu.24107. Epub 2020 Nov 10.
Knight KM, Shelkowitz E, Larson AA, Mirsky DM, Wang Y, Chen T, Wong LJ, Friederich MW, Van Hove JLK. The mitochondrial DNA variant m.9032T > C in MT-ATP6 encoding p.(Leu169Pro) causes a complex mitochondrial neurological syndrome. Mitochondrion. 2020 Nov;55:8-13. doi: 10.1016/j.mito.2020.08.009. Epub 2020 Sep 12.
Falkenberg M, Hirano M. Editing the Mitochondrial Genome. N Engl J Med. 2020 Oct 8;383(15):1489-1491. doi: 10.1056/NEJMcibr2025332.
Almannai M, El-Hattab AW, Ali M, Soler-Alfonso C, Scaglia F. Clinical trials in mitochondrial disorders, an update. Mol Genet Metab. 2020 Sep-Oct;131(1-2):1-13. doi: 10.1016/j.ymgme.2020.10.002. Epub 2020 Oct 6.
Bedoyan JK, Hage R, Shin HK, Linard S, Ferren E, Ducich N, Wilson K, Lehman A, Schillaci LA, Manickam K, Mori M, Bartholomew D, DeBrosse S, Cohen B, Parikh S, Kerr D. Utility of specific amino acid ratios in screening for pyruvate dehydrogenase complex deficiencies and other mitochondrial disorders associated with congenital lactic acidosis and newborn screening prospects. JIMD Rep. 2020 Aug 16;56(1):70-81. doi: 10.1002/jmd2.12153. eCollection 2020 Nov.
Karaa A, Haas R, Goldstein A, Vockley J, Cohen BH. A randomized crossover trial of elamipretide in adults with primary mitochondrial myopathy. J Cachexia Sarcopenia Muscle. 2020 Aug;11(4):909-918. doi: 10.1002/jcsm.12559. Epub 2020 Feb 25.
Dominguez-Gonzalez C, Badosa C, Madruga-Garrido M, Martí I, Paradas C, Ortez C, Diaz-Manera J, Berardo A, Alonso-Pérez J, Trifunov S, Cuadras D, Kalko SG, Blázquez-Bermejo C, Cámara Y, Martí R, Mavillard F, Martin MA, Montoya J, Ruiz-Pesini E, Villarroya J, Montero R, Villarroya F, Artuch R, Hirano M, Nascimento A, Jimenez-Mallebrera C. Growth Differentiation Factor 15 is a potential biomarker of therapeutic response for TK2 deficient myopathy. Sci Rep. 2020 Jun 22;10(1):10111. doi: 10.1038/s41598-020-66940-8.
Shen L, McCormick EM, Muraresku CC, Falk MJ, Gai X. Clinical Bioinformatics in Precise Diagnosis of Mitochondrial Disease. Clin Lab Med. 2020 Jun;40(2):149-161. doi: 10.1016/j.cll.2020.02.002.
Kripps K, Nakayuenyongsuk W, Shayota BJ, Berquist W, Gomez-Ospina N, Esquivel CO, Concepcion W, Sampson JB, Cristin DJ, Jackson WE, Gilliland S, Pomfret EA, Kueht ML, Pettit RW, Sherif YA, Emrick LT, Elsea SH, Himes R, Hirano M, Van Hove JLK, Scaglia F, Enns GM, Larson AA. Successful liver transplantation in mitochondrial neurogastrointestinal encephalomyopathy (MNGIE). Mol Genet Metab. 2020 May;130(1):58-64. doi: 10.1016/j.ymgme.2020.03.001. Epub 2020 Mar 6.
Barca E, Long Y, Cooley V, Schoenaker R, Emmanuele V, DiMauro S, Cohen BH, Karaa A, Vladutiu GD, Haas R, Van Hove JLK, Scaglia F, Parikh S, Bedoyan JK, DeBrosse SD, Gavrilova RH, Saneto RP, Enns GM, Stacpoole PW, Ganesh J, Larson A, Zolkipli-Cunningham Z, Falk MJ, Goldstein AC, Tarnopolsky M, Gropman A, Camp K, Krotoski D, Engelstad K, Rosales XQ, Kriger J, Grier J, Buchsbaum R, Thompson JLP, Hirano M. Mitochondrial diseases in North America: An analysis of the NAMDC Registry. Neurol Genet. 2020 Mar 2;6(2):e402. doi: 10.1212/NXG.0000000000000402. eCollection 2020 Apr.
Berardo A, Emmanuele V, Vargas W, Tanji K, Naini A, Hirano M. Leber hereditary optic neuropathy plus dystonia, and transverse myelitis due to double mutations in MT-ND4 and MT-ND6. J Neurol. 2020 Mar;267(3):823-829. doi: 10.1007/s00415-019-09619-z. Epub 2019 Nov 27.
Friederich MW, Perez FA, Knight KM, Van Hove RA, Yang SP, Saneto RP, Van Hove JLK. Pathogenic variants in NUBPL result in failure to assemble the matrix arm of complex I and cause a complex leukoencephalopathy with thalamic involvement. Mol Genet Metab. 2020 Mar;129(3):236-242. doi: 10.1016/j.ymgme.2019.12.013. Epub 2019 Dec 30.
Saneto RP. Mitochondrial diseases: expanding the diagnosis in the era of genetic testing. J Transl Genet Genom. 2020;4:384-428. doi: 10.20517/jtgg.2020.40. Epub 2020 Sep 29.
Rosales XQ, Thompson JLP, Haas R, Van Hove JLK, Karaa A, Krotoski D, Engelstad K, Buchsbaum R, DiMauro S, Hirano M; North American Mitochondrial Disease Consortium. The North American mitochondrial disease registry. J Transl Genet Genom. 2020;4:81-90. doi: 10.20517/jtgg.2020.12. Epub 2020 Apr 28.
Rosenberg BJ, Hirano M, Quinzii CM, Colantuoni E, Needham DM, Lederer DJ, Baldwin MR. Growth differentiation factor-15 as a biomarker of strength and recovery in survivors of acute respiratory failure. Thorax. 2019 Nov;74(11):1099-1101. doi: 10.1136/thoraxjnl-2019-213621. Epub 2019 Sep 18.
de Barcelos IP, Emmanuele V, Hirano M. Advances in primary mitochondrial myopathies. Curr Opin Neurol. 2019 Oct;32(5):715-721. doi: 10.1097/WCO.0000000000000743.
Sturm G, Cardenas A, Bind MA, Horvath S, Wang S, Wang Y, Hägg S, Hirano M, Picard M. Human aging DNA methylation signatures are conserved but accelerated in cultured fibroblasts. Epigenetics. 2019 Oct;14(10):961-976. doi: 10.1080/15592294.2019.1626651. Epub 2019 Jun 12.
Lopez-Gomez C, Hewan H, Sierra C, Akman HO, Sanchez-Quintero MJ, Juanola-Falgarona M, Tadesse S, Tanji K, Konofagou EE, Hirano M. Bioavailability and cytosolic kinases modulate response to deoxynucleoside therapy in TK2 deficiency. EBioMedicine. 2019 Aug;46:356-367. doi: 10.1016/j.ebiom.2019.07.037. Epub 2019 Aug 2.
Domínguez-González C, Madruga-Garrido M, Mavillard F, Garone C, Aguirre-Rodríguez FJ, Donati MA, Kleinsteuber K, Martí I, Martín-Hernández E, Morealejo-Aycinena JP, Munell F, Nascimento A, Kalko SG, Sardina MD, Álvarez Del Vayo C, Serrano O, Long Y, Tu Y, Levin B, Thompson JLP, Engelstad K, Uddin J, Torres-Torronteras J, Jimenez-Mallebrera C, Martí R, Paradas C, Hirano M. Deoxynucleoside Therapy for Thymidine Kinase 2-Deficient Myopathy. Ann Neurol. 2019 Aug;86(2):293-303. doi: 10.1002/ana.25506. Epub 2019 Jun 17.
Bedoyan JK, Hecht L, Zhang S, Tarrant S, Bergin A, Demirabis D, Wang E, Shin H, Grahame GJ, DeBrosse SD, Hoppel CL, Kerr DS, Berry GT. A novel null mutation in the pyruvate dehydrogenase phosphatase catalytic subunit gene (PDP1) causing pyruvate dehydrogenase complex deficiency. JIMD Rep. 2019 Jun 17;48(1):26-35.
Haas RH. Mitochondrial Dysfunction in Aging and Diseases of Aging. Biology (Basel). 2019 Jun 17;8(2):48. doi: 10.3390/biology8020048.
Barcelos IP, Haas RH. CoQ10 and Aging. Biology (Basel). 2019 May 11;8(2):28. doi: 10.3390/biology8020028.
Domínguez-González C, Hernández-Laín A, Rivas E, Hernández-Voth A, Sayas Catalán J, Fernández-Torrón R, Fuiza-Luces C, García García J, Morís G, Olivé M, Miralles F, Díaz-Manera J, Caballero C, Méndez-Ferrer B, Martí R, García Arumi E, Badosa MC, Esteban J, Jimenez-Mallebrera C, Encinar AB, Arenas J, Hirano M, Martin MÁ, Paradas C. Late-onset thymidine kinase 2 deficiency: a review of 18 cases. Orphanet J Rare Dis. 2019 May 6;14(1):100. doi: 10.1186/s13023-019-1071-z.
Ganetzky RD, Stendel C, McCormick EM, Zolkipli-Cunningham Z, Goldstein AC, Klopstock T, Falk MJ. MT-ATP6 mitochondrial disease variants: Phenotypic and biochemical features analysis in 218 published cases and cohort of 14 new cases. Hum Mutat. 2019 May;40(5):499-515. doi: 10.1002/humu.23723. Epub 2019 Mar 4.
Triska P, Kaneva K, Merkurjev D, Sohail N, Falk MJ, Triche TJ Jr, Biegel JA, Gai X. Landscape of Germline and Somatic Mitochondrial DNA Mutations in Pediatric Malignancies. Cancer Res. 2019 Apr 1;79(7):1318-1330. doi: 10.1158/0008-5472.CAN-18-2220. Epub 2019 Feb 1.
Kubota A, Juanola-Falgarona M, Emmanuele V, Sanchez-Quintero MJ, Kariya S, Sera F, Homma S, Tanji K, Quinzii CM, Hirano M. Cardiomyopathy and altered integrin-actin signaling in Fhl1 mutant female mice. Hum Mol Genet. 2019 Jan 15;28(2):209-219. doi: 10.1093/hmg/ddy299.
Larson AA, Balasubramaniam S, Christodoulou J, Burrage LC, Marom R, Graham BH, Diaz GA, Glamuzina E, Hauser N, Heese B, Horvath G, Mattman A, van Karnebeek C, Lane Rutledge S, Williamson A, Estrella L, Van Hove JKL, Weisfeld-Adams JD. Biochemical signatures mimicking multiple carboxylase deficiency in children with mutations in MT-ATP6. Mitochondrion. 2019 Jan;44:58-64. doi: 10.1016/j.mito.2018.01.001. Epub 2018 Jan 4.
McCormick EM, Zolkipli-Cunningham Z, Falk MJ. Mitochondrial disease genetics update: recent insights into the molecular diagnosis and expanding phenotype of primary mitochondrial disease. Curr Opin Pediatr. 2018 Dec;30(6):714-724. doi: 10.1097/MOP.0000000000000686.
Kleiner G, Barca E, Ziosi M, Emmanuele V, Xu Y, Hidalgo-Gutierrez A, Qiao C, Tadesse S, Area-Gomez E, Lopez LC, Quinzii CM. CoQ(10) supplementation rescues nephrotic syndrome through normalization of H(2)S oxidation pathway. Biochim Biophys Acta Mol Basis Dis. 2018 Nov;1864(11):3708-3722. doi: 10.1016/j.bbadis.2018.09.002. Epub 2018 Sep 6.
Barca E, Ganetzky RD, Potluri P, Juanola-Falgarona M, Gai X, Li D, Jalas C, Hirsch Y, Emmanuele V, Tadesse S, Ziosi M, Akman HO, Chung WK, Tanji K, McCormick EM, Place E, Consugar M, Pierce EA, Hakonarson H, Wallace DC, Hirano M, Falk MJ. USMG5 Ashkenazi Jewish founder mutation impairs mitochondrial complex V dimerization and ATP synthesis. Hum Mol Genet. 2018 Oct 1;27(19):3305-3312. doi: 10.1093/hmg/ddy231.
Siegmund SE, Grassucci R, Carter SD, Barca E, Farino ZJ, Juanola-Falgarona M, Zhang P, Tanji K, Hirano M, Schon EA, Frank J, Freyberg Z. Three-Dimensional Analysis of Mitochondrial Crista Ultrastructure in a Patient with Leigh Syndrome by In Situ Cryoelectron Tomography. iScience. 2018 Aug 31;6:83-91. doi: 10.1016/j.isci.2018.07.014. Epub 2018 Jul 20.
Hoff KE, DeBalsi KL, Sanchez-Quintero MJ, Longley MJ, Hirano M, Naini AB, Copeland WC. Characterization of the human homozygous R182W POLG2 mutation in mitochondrial DNA depletion syndrome. PLoS One. 2018 Aug 29;13(8):e0203198. doi: 10.1371/journal.pone.0203198. eCollection 2018.
Garone C, Taylor RW, Nascimento A, Poulton J, Fratter C, Domínguez-González C, Evans JC, Loos M, Isohanni P, Suomalainen A, Ram D, Hughes MI, McFarland R, Barca E, Lopez Gomez C, Jayawant S, Thomas ND, Manzur AY, Kleinsteuber K, Martin MA, Kerr T, Gorman GS, Sommerville EW, Chinnery PF, Hofer M, Karch C, Ralph J, Cámara Y, Madruga-Garrido M, Domínguez-Carral J, Ortez C, Emperador S, Montoya J, Chakrapani A, Kriger JF, Schoenaker R, Levin B, Thompson JLP, Long Y, Rahman S, Donati MA, DiMauro S, Hirano M. Retrospective natural history of thymidine kinase 2 deficiency. J Med Genet. 2018 Aug;55(8):515-521. doi: 10.1136/jmedgenet-2017-105012. Epub 2018 Mar 30.
Hirano M, Emmanuele V, Quinzii CM. Emerging therapies for mitochondrial diseases. Essays Biochem. 2018 Jul 20;62(3):467-481. doi: 10.1042/EBC20170114. Print 2018 Jul 20.
Torres-Torronteras J, Cabrera-Pérez R, Vila-Julià F, Viscomi C, Cámara Y, Hirano M, Zeviani M, Martí R. Long-Term Sustained Effect of Liver-Targeted Adeno-Associated Virus Gene Therapy for Mitochondrial Neurogastrointestinal Encephalomyopathy. Hum Gene Ther. 2018 Jun;29(6):708-718. doi: 10.1089/hum.2017.133. Epub 2018 Feb 26.
Shen L, Attimonelli M, Bai R, Lott MT, Wallace DC, Falk MJ, Gai X. MSeqDR mvTool: A mitochondrial DNA Web and API resource for comprehensive variant annotation, universal nomenclature collation, and reference genome conversion. Hum Mutat. 2018 Jun;39(6):806-810. doi: 10.1002/humu.23422. Epub 2018 Apr 6.
Zolkipli-Cunningham Z, Xiao R, Stoddart A, McCormick EM, Holberts A, Burrill N, McCormack S, Williams L, Wang X, Thompson JLP, Falk MJ. Mitochondrial disease patient motivations and barriers to participate in clinical trials. PLoS One. 2018 May 17;13(5):e0197513. doi: 10.1371/journal.pone.0197513. eCollection 2018.
Karaa A, Haas R, Goldstein A, Vockley J, Weaver WD, Cohen BH. Randomized dose-escalation trial of elamipretide in adults with primary mitochondrial myopathy. Neurology. 2018 Apr 3;90(14):e1212-e1221. doi: 10.1212/WNL.0000000000005255. Epub 2018 Mar 2.
Grier J, Hirano M, Karaa A, Shepard E, Thompson JLP. Diagnostic odyssey of patients with mitochondrial disease: Results of a survey. Neurol Genet. 2018 Mar 26;4(2):e230. doi: 10.1212/NXG.0000000000000230. PMID: 29600276; PMCID: PMC5873725.
Gramegna LL, Pisano A, Testa C, Manners DN, D'Angelo R, Boschetti E, Giancola F, Pironi L, Caporali L, Capristo M, Valentino ML, Plazzi G, Casali C, Dotti MT, Cenacchi G, Hirano M, Giordano C, Parchi P, Rinaldi R, De Giorgio R, Lodi R, Carelli V, Tonon C. Cerebral Mitochondrial Microangiopathy Leads to Leukoencephalopathy in Mitochondrial Neurogastrointestinal Encephalopathy. AJNR Am J Neuroradiol. 2018 Mar;39(3):427-434. doi: 10.3174/ajnr.A5507. Epub 2018 Jan 18.
Al-Gadi IS, Haas RH, Falk MJ, Goldstein A, McCormack SE. Endocrine Disorders in Primary Mitochondrial Disease. J Endocr Soc. 2018 Feb 19;2(4):361-373. doi: 10.1210/js.2017-00434. eCollection 2018 Apr 1.
Mancuso M, McFarland R, Klopstock T, Hirano M; consortium on Trial Readiness in Mitochondrial Myopathies. International Workshop: Outcome measures and clinical trial readiness in primary mitochondrial myopathies in children and adults. Consensus recommendations. 16-18 November 2016, Rome, Italy. Neuromuscul Disord. 2017 Dec;27(12):1126-1137. doi: 10.1016/j.nmd.2017.08.006. Epub 2017 Sep 8.
Shin HK, Grahame G, McCandless SE, Kerr DS, Bedoyan JK. Enzymatic testing sensitivity, variability and practical diagnostic algorithm for pyruvate dehydrogenase complex (PDC) deficiency. Mol Genet Metab. 2017 Nov;122(3):61-66. doi: 10.1016/j.ymgme.2017.09.001. Epub 2017 Sep 8.
Lopez-Gomez C, Levy RJ, Sanchez-Quintero MJ, Juanola-Falgarona M, Barca E, Garcia-Diaz B, Tadesse S, Garone C, Hirano M. Deoxycytidine and Deoxythymidine Treatment for Thymidine Kinase 2 Deficiency. Ann Neurol. 2017 May;81(5):641-652. doi: 10.1002/ana.24922. Epub 2017 May 4.
Bedoyan JK, Yang SP, Ferdinandusse S, Jack RM, Miron A, Grahame G, DeBrosse SD, Hoppel CL, Kerr DS, Wanders RJA. Lethal neonatal case and review of primary short-chain enoyl-CoA hydratase (SCEH) deficiency associated with secondary lymphocyte pyruvate dehydrogenase complex (PDC) deficiency. Mol Genet Metab. 2017 Apr;120(4):342-349. doi: 10.1016/j.ymgme.2017.02.002. Epub 2017 Feb 2.
Huang X, Bedoyan JK, Demirbas D, Harris DJ, Miron A, Edelheit S, Grahame G, DeBrosse SD, Wong LJ, Hoppel CL, Kerr DS, Anselm I, Berry GT. Succinyl-CoA synthetase (SUCLA2) deficiency in two siblings with impaired activity of other mitochondrial oxidative enzymes in skeletal muscle without mitochondrial DNA depletion. Mol Genet Metab. 2017 Mar;120(3):213-222. doi: 10.1016/j.ymgme.2016.11.005. Epub 2016 Nov 12.
Garone C, Gurgel-Giannetti J, Sanna-Cherchi S, Krishna S, Naini A, Quinzii CM, Hirano M. A Novel SUCLA2 Mutation Presenting as a Complex Childhood Movement Disorder. J Child Neurol. 2017 Feb;32(2):246-250. doi: 10.1177/0883073816666221. Epub 2016 Sep 28.
Kerr DS, Bedoyan JK. Disorders of pyruvate metabolism and the tricarboxylic acid cycle. In Sarafoglou K (ed) Essentials of Pediatric Endocrinology and Metabolism, 2nd Edition, McGraw Hill . 2017
Hirano M, Peters GJ. Advances in purine and pyrimidine metabolism in health and diseases. Nucleosides Nucleotides Nucleic Acids. 2016 Dec;35(10-12):495-501. doi: 10.1080/15257770.2016.1218022.
Al-Mehmadi S, Splitt M; For DDD Study group*, Ramesh V, DeBrosse S, Dessoffy K, Xia F, Yang Y, Rosenfeld JA, Cossette P, Michaud JL, Hamdan FF, Campeau PM, Minassian BA; For CENet Study group‡. FHF1 (FGF12) epileptic encephalopathy. Neurol Genet. 2016 Oct 28;2(6):e115. doi: 10.1212/NXG.0000000000000115. eCollection 2016 Dec.
Pavlakis SG, Hirano M. Mitochondrial Diseases: A Clinical and Molecular History. Pediatr Neurol. 2016 Oct;63:3-5. doi: 10.1016/j.pediatrneurol.2016.05.014. Epub 2016 Jun 2.
Perales-Clemente E, Cook AN, Evans JM, Roellinger S, Secreto F, Emmanuele V, Oglesbee D, Mootha VK, Hirano M, Schon EA, Terzic A, Nelson TJ. Natural underlying mtDNA heteroplasmy as a potential source of intra-person hiPSC variability. EMBO J. 2016 Sep 15;35(18):1979-90. doi: 10.15252/embj.201694892. Epub 2016 Jul 19.
Torres-Torronteras J, Cabrera-Pérez R, Barba I, Costa C, de Luna N, Andreu AL, Barquinero J, Hirano M, Cámara Y, Martí R. Long-Term Restoration of Thymidine Phosphorylase Function and Nucleoside Homeostasis Using Hematopoietic Gene Therapy in a Murine Model of Mitochondrial Neurogastrointestinal Encephalomyopathy. Hum Gene Ther. 2016 Sep;27(9):656-67. doi: 10.1089/hum.2015.160. Epub 2016 May 4.
Karaa A, Kriger J, Grier J, Holbert A, Thompson JL, Parikh S, Hirano M. Mitochondrial disease patients' perception of dietary supplements' use. Mol Genet Metab. 2016 Sep;119(1-2):100-8. doi: 10.1016/j.ymgme.2016.07.005. Epub 2016 Jul 16.
Picard M, Hirano M. Disentangling (Epi)Genetic and Environmental Contributions to the Mitochondrial 3243A>G Mutation Phenotype: Phenotypic Destiny in Mitochondrial Disease?. JAMA Neurol. 2016 Aug 1;73(8):923-5. doi: 10.1001/jamaneurol.2016.1676.
Barca E, Musumeci O, Montagnese F, Marino S, Granata F, Nunnari D, Peverelli L, DiMauro S, Quinzii CM, Toscano A. Cerebellar ataxia and severe muscle CoQ10 deficiency in a patient with a novel mutation in ADCK3. Clin Genet. 2016 Aug;90(2):156-60. doi: 10.1111/cge.12742. Epub 2016 Feb 16.
Saneto RP. Alpers-Huttenlocher syndrome: the role of a multidisciplinary health care team. J Multidiscip Healthc. 2016 Jul 26;9:323-33. doi: 10.2147/JMDH.S84900. eCollection 2016.
Yamada M, Emmanuele V, Sanchez-Quintero MJ, Sun B, Lallos G, Paull D, Zimmer M, Pagett S, Prosser RW, Sauer MV, Hirano M, Egli D. Genetic Drift Can Compromise Mitochondrial Replacement by Nuclear Transfer in Human Oocytes. Cell Stem Cell. 2016 Jun 2;18(6):749-754. doi: 10.1016/j.stem.2016.04.001. Epub 2016 May 19.
Shen L, Diroma MA, Gonzalez M, Navarro-Gomez D, Leipzig J, Lott MT, van Oven M, Wallace DC, Muraresku CC, Zolkipli-Cunningham Z, Chinnery PF, Attimonelli M, Zuchner S, Falk MJ, Gai X. MSeqDR: A Centralized Knowledge Repository and Bioinformatics Web Resource to Facilitate Genomic Investigations in Mitochondrial Disease. Hum Mutat. 2016 Jun;37(6):540-548. doi: 10.1002/humu.22974. Epub 2016 Mar 21.
Merkel PA, Manion M, Gopal-Srivastava R, Groft S, Jinnah HA, Robertson D, Krischer JP; Rare Diseases Clinical Research Network. The partnership of patient advocacy groups and clinical investigators in the rare diseases clinical research network. Orphanet J Rare Dis. 2016 May 18;11(1):66. doi: 10.1186/s13023-016-0445-8.
Engelstad K, Sklerov M, Kriger J, Sanford A, Grier J, Ash D, Egli D, DiMauro S, Thompson JL, Sauer MV, Hirano M. Attitudes toward prevention of mtDNA-related diseases through oocyte mitochondrial replacement therapy. Hum Reprod. 2016 May;31(5):1058-65. doi: 10.1093/humrep/dew033. Epub 2016 Mar 2.
Marin SE, Saneto RP. Neuropsychiatric Features in Primary Mitochondrial Disease. Neurol Clin. 2016 Feb;34(1):247-94. doi: 10.1016/j.ncl.2015.08.011.
Halter JP, Michael W, Schüpbach M, Mandel H, Casali C, Orchard K, Collin M, Valcarcel D, Rovelli A, Filosto M, Dotti MT, Marotta G, Pintos G, Barba P, Accarino A, Ferra C, Illa I, Beguin Y, Bakker JA, Boelens JJ, de Coo IF, Fay K, Sue CM, Nachbaur D, Zoller H, Sobreira C, Pinto Simoes B, Hammans SR, Savage D, Martí R, Chinnery PF, Elhasid R, Gratwohl A, Hirano M. Allogeneic haematopoietic stem cell transplantation for mitochondrial neurogastrointestinal encephalomyopathy. Brain. 2015 Oct;138(Pt 10):2847-58. doi: 10.1093/brain/awv226. Epub 2015 Aug 10.
Gonzalez M, Falk MJ, Gai X, Postrel R, Schüle R, Zuchner S. Innovative genomic collaboration using the GENESIS (GEM.app) platform. Hum Mutat. 2015 Oct;36(10):950-6. doi: 10.1002/humu.22836. Epub 2015 Aug 12.
Parikh S, Goldstein A, Koenig MK, Scaglia F, Enns GM, Saneto R, Anselm I, Cohen BH, Falk MJ, Greene C, Gropman AL, Haas R, Hirano M, Morgan P, Sims K, Tarnopolsky M, Van Hove JL, Wolfe L, DiMauro S. Diagnosis and management of mitochondrial disease: a consensus statement from the Mitochondrial Medicine Society. Genet Med. 2015 Sep;17(9):689-701. doi: 10.1038/gim.2014.177. Epub 2014 Dec 11.
Ferdinandusse S, Friederich MW, Burlina A, Ruiter J, Coughlin CR, Dishop MK, Gallagher RC, Bedoyan JK, Vaz FM, Waterham HR, Gowan K, Chatfield K, Bennett MJ, Elpeleg O, Van Hove JLK, Wanders RJA. Clinical and biochemical characterization of four patients with mutations in ECHS1. Orphanet J Rare Dis. 2015 Jun 18;10:79.
Navarro-Gomez D, Leipzig J, Shen L, Lott M, Stassen AP, Wallace DC, Wiggs JL, Falk MJ, van Oven M, Gai X. Phy-Mer: a novel alignment-free and reference-independent mitochondrial haplogroup classifier. Bioinformatics. 2015 Apr 15;31(8):1310-2. doi: 10.1093/bioinformatics/btu825. Epub 2014 Dec 12.
Falk MJ, Shen L, Gonzalez M, Leipzig J, Lott MT, Stassen AP, Diroma MA, Navarro-Gomez D, Yeske P, Bai R, Boles RG, Brilhante V, Ralph D, DaRe JT, Shelton R, Terry SF, Zhang Z, Copeland WC, van Oven M, Prokisch H, Wallace DC, Attimonelli M, Krotoski D, Zuchner S, Gai X; MSeqDR Consortium Participants; MSeqDR Consortium participants: Sherri Bale, Jirair Bedoyan, Doron Behar, Penelope Bonnen, Lisa Brooks, Claudia Calabrese, Sarah Calvo, Patrick Chinnery, John Christodoulou, Deanna Church,; Rosanna Clima, Bruce H Cohen, Richard G Cotton, IFM de Coo, Olga Derbenevoa, Johan T den Dunnen, David Dimmock, Gregory Enns, Giuseppe Gasparre,; Amy Goldstein, Iris Gonzalez, Katrina Gwinn, Sihoun Hahn, Richard H Haas, Hakon Hakonarson, Michio Hirano, Douglas Kerr, Dong Li, Maria Lvova, Finley Macrae, Donna Maglott, Elizabeth McCormick, Grant Mitchell, Vamsi K Mootha, Yasushi Okazaki,; Aurora Pujol, Melissa Parisi, Juan Carlos Perin, Eric A Pierce, Vincent Procaccio, Shamima Rahman, Honey Reddi, Heidi Rehm, Erin Riggs, Richard Rodenburg, Yaffa Rubinstein, Russell Saneto, Mariangela Santorsola, Curt Scharfe,; Claire Sheldon, Eric A Shoubridge, Domenico Simone, Bert Smeets, Jan A Smeitink, Christine Stanley, Anu Suomalainen, Mark Tarnopolsky, Isabelle Thiffault, David R Thorburn, Johan Van Hove, Lynne Wolfe, and Lee-Jun Wong. Mitochondrial Disease Sequence Data Resource (MSeqDR): a global grass-roots consortium to facilitate deposition, curation, annotation, and integrated analysis of genomic data for the mitochondrial disease clinical and research communities. Mol Genet Metab. 2015 Mar;114(3):388-96. doi: 10.1016/j.ymgme.2014.11.016. Epub 2014 Dec 4.
Ruhoy IS, Saneto RP. The genetics of Leigh syndrome and its implications for clinical practice and risk management. Appl Clin Genet. 2014 Nov 13;7:221-34. doi: 10.2147/TACG.S46176. eCollection 2014.
Balreira A, Boczonadi V, Barca E, Pyle A, Bansagi B, Appleton M, Graham C, Hargreaves IP, Rasic VM, Lochmüller H, Griffin H, Taylor RW, Naini A, Chinnery PF, Hirano M, Quinzii CM, Horvath R. ANO10 mutations cause ataxia and coenzyme Q₁₀ deficiency. J Neurol. 2014 Nov;261(11):2192-8. doi: 10.1007/s00415-014-7476-7. Epub 2014 Sep 3.
Deeb KK, Bedoyan JK, Wang R, Sremba L, Schroeder MC, Grahame GJ, Boyer M, McCandless SE, Kerr DS, Zhang S. Somatic mosaicism for a novel PDHA1 mutation in a male with severe pyruvate dehydrogenase complex deficiency. Mol Genet Metab. 2014 Aug 28;1:362-367.
Garone C, Garcia-Diaz B, Emmanuele V, Lopez LC, Tadesse S, Akman HO, Tanji K, Quinzii CM, Hirano M. Deoxypyrimidine monophosphate bypass therapy for thymidine kinase 2 deficiency. EMBO Mol Med. 2014 Aug;6(8):1016-27. doi: 10.15252/emmm.201404092.
Peverelli L, Gold CA, Naini AB, Tanji K, Akman HO, Hirano M, Dimauro S. Mitochondrial myopathy with dystrophic features due to a novel mutation in the MTTM gene. Muscle Nerve. 2014 Aug;50(2):292-5. doi: 10.1002/mus.24262.
Quinzii CM, Hirano M, DiMauro S. Mutant COQ2 in multiple-system atrophy. N Engl J Med. 2014 Jul 3;371(1):81-2. doi: 10.1056/NEJMc1311763.
Quinzii CM, Emmanuele V, Hirano M. Clinical presentations of coenzyme q10 deficiency syndrome. Mol Syndromol. 2014 Jul;5(3-4):141-6. doi: 10.1159/000360490.
Garcia-Diaz B, Garone C, Barca E, Mojahed H, Gutierrez P, Pizzorno G, Tanji K, Arias-Mendoza F, Quinzii CM, Hirano M. Deoxynucleoside stress exacerbates the phenotype of a mouse model of mitochondrial neurogastrointestinal encephalopathy. Brain. 2014 May;137(Pt 5):1337-49. doi: 10.1093/brain/awu068. Epub 2014 Apr 10.
Torres-Torronteras J, Viscomi C, Cabrera-Pérez R, Cámara Y, Di Meo I, Barquinero J, Auricchio A, Pizzorno G, Hirano M, Zeviani M, Martí R. Gene therapy using a liver-targeted AAV vector restores nucleoside and nucleotide homeostasis in a murine model of MNGIE. Mol Ther. 2014 May;22(5):901-7. doi: 10.1038/mt.2014.6. Epub 2014 Jan 22..
Hirano M. Weighing in on Leber hereditary optic neuropathy: effects of mitochondrial mass. Brain. 2014 Feb;137(Pt 2):308-9. doi: 10.1093/brain/awu005.
Paradas C, Akman HO, Ionete C, Lau H, Riskind PN, Jones DE, Smith TW, Hirano M, Dimauro S. Branching enzyme deficiency: expanding the clinical spectrum. JAMA Neurol. 2014 Jan;71(1):41-7. doi: 10.1001/jamaneurol.2013.4888.
Paradas C, Camaño P, Otaegui D, Oz O, Emmanuele V, DiMauro S, Hirano M. Longitudinal clinical follow-up of a large family with the R357P Twinkle mutation. JAMA Neurol. 2013 Nov;70(11):1425-8. doi: 10.1001/jamaneurol.2013.3185.
Pfeffer G, Horvath R, Klopstock T, Mootha VK, Suomalainen A, Koene S, Hirano M, Zeviani M, Bindoff LA, Yu-Wai-Man P, Hanna M, Carelli V, McFarland R, Majamaa K, Turnbull DM, Smeitink J, Chinnery PF. New treatments for mitochondrial disease-no time to drop our standards. Nat Rev Neurol. 2013 Aug;9(8):474-81. doi: 10.1038/nrneurol.2013.129. Epub 2013 Jul 2.
DiMauro S. Mitochondrial encephalomyopathies--fifty years on: the Robert Wartenberg Lecture. Neurology. 2013 Jul 16;81(3):281-91. doi: 10.1212/WNL.0b013e31829bfe89.
Melià MJ, Kubota A, Ortolano S, Vílchez JJ, Gámez J, Tanji K, Bonilla E, Palenzuela L, Fernández-Cadenas I, Pristoupilová A, García-Arumí E, Andreu AL, Navarro C, Hirano M, Martí R. Limb-girdle muscular dystrophy 1F is caused by a microdeletion in the transportin 3 gene. Brain. 2013 May;136(Pt 5):1508-17. doi: 10.1093/brain/awt074. Epub 2013 Mar 29.
Saneto RP, Sedensky MM. Mitochondrial disease in childhood: mtDNA encoded. Neurotherapeutics. 2013 Apr;10(2):199-211. doi: 10.1007/s13311-012-0167-0.
Saneto RP, Cohen BH, Copeland WC, Naviaux RK. Alpers-Huttenlocher syndrome. Pediatr Neurol. 2013 Mar;48(3):167-78. doi: 10.1016/j.pediatrneurol.2012.09.014.
Gurgel-Giannetti J, Oliveira G, Brasileiro Filho G, Martins P, Vainzof M, Hirano M. Mitochondrial cardioencephalomyopathy due to a novel SCO2 mutation in a Brazilian patient: case report and literature review. JAMA Neurol. 2013 Feb;70(2):258-61. doi: 10.1001/jamaneurol.2013.595.
Garone C, Rubio JC, Calvo SE, Naini A, Tanji K, Dimauro S, Mootha VK, Hirano M. MPV17 Mutations Causing Adult-Onset Multisystemic Disorder With Multiple Mitochondrial DNA Deletions. Arch Neurol. 2012 Dec;69(12):1648-51. doi: 10.1001/archneurol.2012.405.
Neeve VC, Samuels DC, Bindoff LA, van den Bosch B, Van Goethem G, Smeets H, Lombès A, Jardel C, Hirano M, Dimauro S, De Vries M, Smeitink J, Smits BW, de Coo IF, Saft C, Klopstock T, Keiling BC, Czermin B, Abicht A, Lochmüller H, Hudson G, Gorman GG, Turnbull DM, Taylor RW, Holinski-Feder E, Chinnery PF, Horvath R. What is influencing the phenotype of the common homozygous polymerase-γ mutation p.Ala467Thr?. Brain. 2012 Dec;135(Pt 12):3614-26. doi: 10.1093/brain/aws298.
Garcia-Diaz B, Barros MH, Sanna-Cherchi S, Emmanuele V, Akman HO, Ferreiro-Barros CC, Horvath R, Tadesse S, El Gharaby N, DiMauro S, De Vivo DC, Shokr A, Hirano M, Quinzii CM. Infantile encephaloneuromyopathy and defective mitochondrial translation are due to a homozygous RMND1 mutation. Am J Hum Genet. 2012 Oct 5;91(4):729-36. doi: 10.1016/j.ajhg.2012.08.019. Epub 2012 Sep 27.
Ash DB, Papadimitriou D, Hays AP, Dimauro S, Hirano M. A novel mutation in PNPLA2 leading to neutral lipid storage disease with myopathy. Arch Neurol. 2012 Sep;69(9):1190-2. doi: 10.1001/archneurol.2011.2600.
Gurgel-Giannetti J, Camargos ST, Cardoso F, Hirano M, DiMauro S. POLG1 Arg953Cys mutation: expanded phenotype and recessive inheritance in a Brazilian family. Muscle Nerve. 2012 Mar;45(3):453-4. doi: 10.1002/mus.22330.
Rahman S, Clarke CF, Hirano M. 176th ENMC International Workshop: diagnosis and treatment of coenzyme Q(1)(0) deficiency. Neuromuscul Disord. Jan 2012;22(1):76-86. PMID: 21723727, PMCID: PMC3222743.
Kurt B, Naini AB, Copeland WC, Lu J, Dimauro S, Hirano M. A novel POLG gene mutation in a patient with SANDO. J Exp Integr Med. 2012;2(2):10.5455/jeim.200312.cr.001. doi: 10.5455/jeim.200312.cr.001.
Marti R, Lopez LC, Hirano M. Assessment of thymidine phosphorylase function: measurement of plasma thymidine (and deoxyuridine) and thymidine phosphorylase activity. Methods Mol Biol. 2012;837:121-133. PMID: 22215544, PMCID: PMC4942128.
Martí R, Dorado B, Hirano M. Measurement of mitochondrial dNTP pools. Methods Mol Biol. 2012;837:135-48. doi: 10.1007/978-1-61779-504-6_9.
Kaufmann P, Engelstad K, Wei Y, Kulikova R, Oskoui M, Sproule DM, Battista V, Koenigsberger DY, Pascual JM, Shanske S, Sano M, Mao X, Hirano M, Shungu DC, Dimauro S, De Vivo DC. Natural history of MELAS associated with mitochondrial DNA m.3243A>G genotype. Neurology. 2011 Nov 29;77(22):1965-71. doi: 10.1212/WNL.0b013e31823a0c7f. Epub 2011 Nov 16.
Quinzii CM, Hirano M. Primary and secondary CoQ(10) deficiencies in humans. Biofactors. Sep 2011;37(5):361-365. PMID: 21990098, PMCID: PMC3258494.
Torres-Torronteras J, Gómez A, Eixarch H, Palenzuela L, Pizzorno G, Hirano M, Andreu AL, Barquinero J, Martí R. Hematopoietic gene therapy restores thymidine phosphorylase activity in a cell culture and a murine model of MNGIE. Gene Ther. 2011 Aug;18(8):795-806. doi: 10.1038/gt.2011.24. Epub 2011 Mar 31.
Villarroya J, Lara MC, Dorado B, Garrido M, García-Arumí E, Meseguer A, Hirano M, Vilà MR. Targeted impairment of thymidine kinase 2 expression in cells induces mitochondrial DNA depletion and reveals molecular mechanisms of compensation of mitochondrial respiratory activity. Biochem Biophys Res Commun. 2011 Apr 8;407(2):333-8. doi: 10.1016/j.bbrc.2011.03.018. Epub 2011 Mar 5.
Halter J, Schüpbach W, Casali C, Elhasid R, Fay K, Hammans S, Illa I, Kappeler L, Krähenbühl S, Lehmann T, Mandel H, Marti R, Mattle H, Orchard K, Savage D, Sue CM, Valcarcel D, Gratwohl A, Hirano M. Allogeneic hematopoietic SCT as treatment option for patients with mitochondrial neurogastrointestinal encephalomyopathy (MNGIE): a consensus conference proposal for a standardized approach. Bone Marrow Transplant. 2011 Mar;46(3):330-337. doi: 10.1038/bmt.2010.100. Epub 2010 May 3.
Dorado B, Area E, Akman HO, Hirano M. Onset and organ specificity of Tk2 deficiency depends on Tk1 down-regulation and transcriptional compensation. Hum Mol Genet. Jan 1 2011;20(1):155-164. PMID: 20940150, PMCID: PMC3000681.
Villarroya J, Dorado B, Vilà MR, Garcia-Arumí E, Domingo P, Giralt M, Hirano M, Villarroya F. Thymidine kinase 2 deficiency-induced mitochondrial DNA depletion causes abnormal development of adipose tissues and adipokine levels in mice. PLoS One. 2011;6(12):e29691. doi: 10.1371/journal.pone.0029691. Epub 2011 Dec 27.
Tanji K, Kaufmann P, Naini AB, Lu J, Parsons TC, Wang D, Willey JZ, Shanske S, Hirano M, Bonilla E, Khandji A, Dimauro S, Rowland LP. A novel tRNA(Val) mitochondrial DNA mutation causing MELAS. J Neurol Sci. 2008 Jul 15;270(1-2):23-7. doi: 10.1016/j.jns.2008.01.016. Epub 2008 Mar 7.
Holmes BM, Hollander S, Sacharow S. Perspectives and Insights Into Phenylketonuria: Patient Narratives About the Early Years Following Newborn Screening. Am J Med Genet C Semin Med Genet. 2024 Sep 17:e32110. doi: 10.1002/ajmg.c.32110. Epub ahead of print. PMID: 39285733.
Phenylketonuria (PKU) is a genetic metabolic disorder that increases the body's levels of the amino acid phenylalanine, which can build up to harmful levels if left untreated. Newborn screening for PKU began in 1963. Over the following decades, knowledge and treatment recommendations have evolved, with individual and family experiences varying widely.
In this essay, authors share patient stories about the early years following newborn screening for PKU. The team recorded interviews with patients born in the first 25 years after newborn screening for PKU began. While some of these patients were actively followed in the PKU clinic, others had been out of the clinic for many years.
The resulting stories describe different individual experiences, including diet discontinuation in childhood, changing treatment guidelines, and new treatments that have become available. Authors note that these stories highlight the challenges of the early years of newborn screening, when best practices were being discovered through trial and error.
Christ SE, Arnold G, Lichter-Konecki U, Berry GT, Grange DK, Harding CO, Jurecki E, Levy H, Longo N, Morotti H, Sacharow S, Thomas J, White DA. Initial results from the PHEFREE longitudinal natural history study: Cross-sectional observations in a cohort of individuals with phenylalanine hydroxylase (PAH) deficiency. Mol Genet Metab. 2024 Jul 22;143(1-2):108541. doi: 10.1016/j.ymgme.2024.108541. Epub ahead of print. PMID: 39059270.
Phenylalanine hydroxylase (PAH) deficiency, also known as phenylketonuria (PKU), is a genetic metabolic disorder that increases the body's levels of the amino acid phenylalanine. The last large-scale natural history study of individuals with PKU in the United States was conducted over 50 years ago. Since then, there have been significant changes in treatment recommendations and options.
In this study, researchers report initial data from the PHEFREE natural history study of individuals with PKU. The team describes the structure and methods of the study, including data from 73 participants.
Authors note that this study could help validate new neurocognitive tools for assessing individuals with PKU, as well as evaluating the long-term effects of changes in metabolic control on patient outcomes.
Martinez M, Harding CO, Schwank G, Thöny B. State-of-the-art 2023 on gene therapy for phenylketonuria. J Inherit Metab Dis. 2024 Jan;47(1):80-92. doi: 10.1002/jimd.12651. Epub 2023 Aug 3. PMID: 37401651; PMCID: PMC10764640
Phenylketonuria (PKU) is a genetic metabolic disorder that increases the body's levels of the amino acid phenylalanine, which can build up to harmful levels if left untreated. Patients with PKU are treated with dietary therapy. However, these dietary restrictions are complicated and often difficult to follow, highlighting the need for new therapies and ultimately a cure.
In this review paper, researchers summarize, compare, and evaluate state-of-the-art gene therapy approaches for PKU. Methods include recombinant viral and non-viral vector delivery; gene addition; genome, gene, or base editing; and gene insertion or replacement. A list of current and planned clinical trials for PKU gene therapy is also included.
Authors note that this review can help advance scientific understanding and efficacy testing, paving the way for safe and efficient therapies for patients with PKU.
van Spronsen FJ, Blau N, Harding C, Burlina A, Longo N, Bosch AM. Phenylketonuria. Nat Rev Dis Primers. 2021 May 20;7(1):36. doi: 10.1038/s41572-021-00267-0.
Phenylketonuria (PKU; also known as phenylalanine hydroxylase (PAH) deficiency) is an autosomal recessive disorder of phenylalanine metabolism, in which especially high phenylalanine concentrations cause brain dysfunction. If untreated, this brain dysfunction results in severe intellectual disability, epilepsy and behavioural problems. Even though PAH deficiency is the most common defect of amino acid metabolism in humans, brain dysfunction in individuals with PKU is still not well understood and further research is needed to facilitate development of pathophysiology-driven treatments.
Manzoni F, Salvatici E, Burlina A, Andrews A, Pasquali M, Longo N. Retrospective analysis of 19 patients with 6-Pyruvoyl Tetrahydropterin Synthase Deficiency: Prolactin levels inversely correlate with growth. Mol Genet Metab. 2020 Dec;131(4):380-389. doi: 10.1016/j.ymgme.2020.11.004. Epub 2020 Nov 18. PMID: 33234470; PMCID: PMC7749858.
Pyruvoyl Tetrahydropterin Synthase (PTPS) Deficiency is the most common form of BH4 (tetrahydrobiopterin) deficiency resulting in hyperphenylalaninemia. It can have variable clinical severity and there is limited information on the clinical presentation, natural history and effectiveness of newborn screening for this condition.
Harding CO. Prospects for Cell-Directed Curative Therapy of Phenylketonuria (PKU). Mol Front J. 2019 Dec;3(2):110-121. doi: 10.1142/s2529732519400145. Epub 2019 Dec 12. PMID: 32524084; PMCID: PMC7286632.
This review discusses the potential for and the limitations of permanently curative cell-directed treatment of PKU (phenylketonuria, also known as phenylalanine hydroxylase (PAH) deficiency), including liver-directed gene therapy and gene editing, if initiated during early infancy.
Breilyn MS, Simpson K, Elsbecker SA, Barber JR, Bryan K, Berry SA. Maternal Health Outcomes in Ornithine Transcarbamylase Deficiency: A Comparative Analysis of Pregnancies in Symptomatic and Asymptomatic Heterozygotes. Mol Genet Metab. Mol Genet Metab. 2025 April;144(4):109083. doi: 10.1016/j.ymgme.2025.109083
Zielonka M, Kölker S, Garbade SF, Gleich F, Nagamani SCS, Gropman AL, Druck AC, Ramdhouni N, Göde L, Hoffmann GF, Posset R. Severity-adjusted evaluation of initial dialysis on short-term health outcomes in urea cycle disorders.. Molecular Genetics and Metabolism. Zielonka M, Kölker S, Garbade SF, Gleich F, Nagamani SCS, Gropman AL, Druck AC, Ramdhouni N, Göde L, Hoffmann GF, Posset R; Urea Cycle Disorders Consortium (UCDC). Severity-adjusted evaluation of initial dialysis on short-term health outcomes in urea cycle disorders. Mol Genet Metab. 2024 Sep-Oct;143(1-2):108566. doi: 10.1016/j.ymgme.2024.108566. Epub 2024 Aug 19. PMID: 39299137.
Chanvanichtrakool M, Schreiber JM, Chen WL, Barber J, Zhang A, Ah Mew N, Schulze A, Wilkening G, Nagamani SCS, Gropman A; Urea Cycle Disease Consortium. Unraveling the Link: Seizure Characteristics and Ammonia Levels in Urea Cycle Disorder during Hyperammonemic Crises. Pediatr Neurol. 2024 Oct;159:48-55. doi: 10.1016/j.pediatrneurol.2024.06.013. Epub 2024 Jun 29. PMID: 39121557; PMCID: PMC11381174.
Urea cycle disorders (UCDs) are a group of inherited, metabolic disorders characterized by hyperammonemia (high blood ammonia levels). Individuals with UCDs may experience symptoms including developmental delays, buildup of fluid around the brain, and seizures.
In this study, researchers investigated the link between seizures and hyperammonemic crises in individuals with UCDs. Among 85 UCD patients, the team reviewed medical records for evidence of seizures during hyperammonemic crises as well as initial levels of ammonia and glutamine.
Results showed that 66% of UCD patients experienced hyperammonemic crises, with 13% of these patients experiencing seizures. Findings also revealed that initial ammonia and glutamine levels can help determine the risk of seizures. Authors note that this study highlights the utility of electroencephalogram monitoring during crises for patients who present with clinical seizures or who have encephalopathy (brain disease) with high ammonia levels.
Sen K, Izem R, Long Y, Jiang J, Konczal LL, McCarter RJ; Members of the Urea Cycle Disorders Consortium (UCDC); Gropman AL, Bedoyan JK. Are asymptomatic carriers of OTC deficiency always asymptomatic? A multicentric retrospective study of risk using the UCDC longitudinal study database. Mol Genet Geonomic Med. 2024 Apr;12(4):e2443. doi: 10.1002/mgg3.2443. PMID: 38634223; PMCID: PMC11024633.
Ornithine transcarbamylase deficiency (OTCD) is a type of urea cycle disorder characterized by hyperammonemia (high blood ammonia levels) due to deficiency or absence of an enzyme needed to convert nitrogen from protein into urea (a waste product). Because OTCD is caused by an X-linked mutation in the OTC gene, the majority of patients with severe presentation of OTC deficiency are male, as they have only one X chromosome. Although 80% of females with OTCD are typically thought to remain asymptomatic, not much is known about their clinical characteristics and long-term health vulnerabilities.
In this study, researchers explored the factors that might predict development of defined complications and serious illness in apparent asymptomatic females with OTCD. The team reviewed data from 302 females enrolled in the Urea Cycle Disorders Consortium (UCDC) longitudinal natural history study. Researchers also performed several types of neuroimaging studies in a female patient with OTCD.
Results show that these patients can experience neuropsychiatric and behavioral symptoms as well as an increased risk of hyperammonemia later in life, demonstrating that asymptomatic females with OTCD are not always asymptomatic. Authors note that these findings can aid in the development of a risk calculator and improve guidelines for management of these patients, paving the way for potential new therapies.
Posset R, Garbade SF, Gleich F, Nagamani SCS, Gropman AL, Epp F, Ramdhouni N, Druck AC, Hoffmann GF, Kölker S, Zielonka M; Urea Cycle Disorders Consortium (UCDC) and the European registry and network for Intoxication type Metabolic Diseases (E-IMD) consortia study group. Impact of supplementation with L-citrulline/arginine after liver transplantation in individuals with Urea Cycle Disorders. Mol Genet Metab. 2024 Mar;141(3):108112. doi: 10.1016/j.ymgme.2023.108112. Epub 2023 Dec 10. PMID: 38301530.
Urea cycle disorders (UCDs) are genetic disorders that result in a deficiency of one of the six enzymes in the urea cycle, causing hyperammonemia (high blood ammonia levels). When medical management is not enough to prevent hyperammonemia, patients with UCDs may undergo liver transplantation. Both before and after transplant, these patients often receive L-citrulline or L-arginine supplements to help their bodies eliminate ammonia. However, not much is known about the impact of long-term supplementation.
In this pilot study, researchers investigated the effects of long-term L-citrulline or L-arginine supplementation in patients with UCDs who have undergone liver transplantation. The team used data collected from longitudinal observational studies to compare outcomes of 16 patients who received these supplements long-term with 36 patients who were not supplemented over the course of 4 or 5 years after transplant.
Results suggest that although supplementation with L-citrulline or L-arginine is often continued after transplant, in this pilot study, such supplementation was not associated with health-related outcomes or biochemical responses. Authors note that analyzing larger samples over longer observation periods will provide more insight into the usefulness of long-term supplementation.
Posset R, Garbade SF, Gleich F, Scharre S, Okun JG, Gropman AL, Nagamani SCS, Druck AC, Epp F, Hoffmann GF, Kölker S, Zielonka M; Urea Cycle Disorders Consortium (UCDC); European registry and network for Intoxication type Metabolic Diseases (E-IMD) Consortia Study Group. Severity-adjusted evaluation of liver transplantation on health outcomes in urea cycle disorders. Genet Med. 2023 Dec 3;26(4):101039. doi: 10.1016/j.gim.2023.101039. Epub ahead of print. PMID: 38054409.
Urea cycle disorders (UCDs) are a group of inherited, metabolic disorders characterized by hyperammonemia (high blood ammonia levels). Patients with UCD may undergo liver transplantation when medical management is not enough to prevent hyperammonemia. However, not much is known about how the effects of transplant compare to medical management alone.
In this study, researchers classified patients into “severe” and “attenuated” categories based on genetic information and a novel enzyme activity test. Then, using data collected from longitudinal observational studies, they compared the health-related outcomes in patients who underwent liver transplantation vs medical management.
Results show that liver transplantation led to greater metabolic stability without the need for protein restriction or nitrogen-scavenging therapy. However, while transplantation led to more favorable growth outcomes, it was not associated with improved neurocognitive outcomes compared to long-term medical management.
Lichter-Konecki U, Sanz JH; Urea Cycle Disorders Consortium; McCarter R. Relationship between longitudinal changes in neuropsychological outcome and disease biomarkers in urea cycle disorders. Pediatr Res. 2023 Dec;94(6):2005-2015. doi: 10.1038/s41390-023-02722-y. Epub 2023 Jul 15.
Glinton KE, Minard CG, Liu N, Sun Q, Elsea SH, Burrage LC, Nagamani SCS. Monitoring the treatment of urea cycle disorders using phenylbutyrate metabolite analyses: Still many lessons to learn. Mol Genet Metab. 2023 Nov;140(3):107699. doi: 10.1016/j.ymgme.2023.107699. Epub 2023 Sep 11.
Posset R, Zielonka M, Gleich F, Garbade SF, Hoffmann GF, Kölker S; Urea Cycle Disorders Consortium (UCDC) and European registry and network for Intoxication type Metabolic Diseases (E-IMD) Consortia Study Group. The challenge of understanding and predicting phenotypic diversity in urea cycle disorders. J Inherit Metab Dis. 2023 Nov;46(6):1007-1016. doi: 10.1002/jimd.12678. Epub 2023 Oct 10.
Murali CN, Barber JR, McCarter R, Zhang A, Gallant N, Simpson K, Dorrani N, Wilkening GN, Hays RD, Lichter-Konecki U; Members of the Urea Cycle Disorders Consortium; Burrage LC, Nagamani SCS. Health-related quality of life in a systematically assessed cohort of children and adults with urea cycle disorders. Mol Genet Metab. 2023 Sep 8;140(3):107696. doi: 10.1016/j.ymgme.2023.107696. Epub ahead of print. PMID: 37690181
Urea cycle disorders (UCDs) are a group of inherited, metabolic disorders characterized by hyperammonemia (high blood ammonia levels). Accumulation of ammonia is toxic to the nervous system, resulting in neurological symptoms that can impact health-related quality of life (HRQoL). However, only a few studies have systematically investigated the impact of UCDs on HRQoL.
In this study, researchers assessed HRQoL in a large cohort of children and adults with UCDs. The team reviewed HRQoL and clinical data from a Urea Cycle Disorders Consortium longitudinal study; compared to healthy individuals and those with PKU and diabetes; and assessed relationships between HRQoL, UCD diagnosis, and disease severity.
Results show that individuals with UCDs have worse HRQoL compared to healthy individuals and those with PKU and diabetes. Authors state that future work should focus on the impact of liver transplantation and other clinical variables on HRQoL in UCDs.
Ladha FA, Le Mons C, Craigen WJ, Magoulas PL, Marom R, Lewis AM. Barriers to a successful healthcare transition for individuals with urea cycle disorders. Mol Genet Metab. 2023 Jul;139(3):107609. doi: 10.1016/j.ymgme.2023.107609. Epub 2023 May 15.
Scharre S, Posset R, Garbade SF, Gleich F, Seidl MJ, Druck AC, Okun JG, Gropman AL, Nagamani SCS, Hoffmann GF, Kölker S, Zielonka M; Urea Cycle Disorders Consortium (UCDC) and the European registry and network for Intoxication type Metabolic Diseases (E-IMD) Consortia Study Group. Predicting the disease severity in male individuals with ornithine transcarbamylase deficiency. Ann Clin Transl Neurol. 2022 Oct 10. doi: 10.1002/acn3.51668. Epub ahead of print. PMID: 36217298.
Ornithine transcarbamylase deficiency (OTC-D) is an X-linked disorder and the most common type of urea cycle disorder. Patients with OTC-D can present with a variable spectrum of disease severity, ranging from no symptoms to lethal hyperammonemia (high blood ammonia levels). Therefore, predicting disease course at an early stage is important to personalize therapies for individual patients, which can include medical treatment or liver transplantation. In this study, researchers developed a new cell-based system to assess the residual enzyme activity associated with various disease-causing genetic changes in the OTC gene. Using this system, they were able to correlate residual enzymatic OTC activities with clinical and biochemical outcome parameters of 119 male individuals with OTC-D. Results show that residual enzymatic OTC activity can distinguish individuals with a severe form of OTC-D from those with milder forms of the disorder. As a reliable predictor of disease severity in OTC-D, this classification system could help guide therapeutic strategies and counseling of patients and parents.
Khaksari K, Chen WL, Gropman AL. Review of Applications of Near-Infrared Spectroscopy in Two Rare Disorders with Executive and Neurological Dysfunction: UCD and PKU. Genes (Basel). 2022 Sep 21;13(10):1690. doi: 10.3390/genes13101690. PMID: 36292574; PMCID: PMC9602148.
Urea cycle disorders (UCD) and phenylketonuria (PKU) are two types of genetic, metabolic disorders characterized by neurological symptoms. As with many rare diseases, small population size can make these disorders challenging to study. Tools such as functional neuroimaging are developed to help generate biomarkers, collect baseline data, and measure treatment effects in patients with neurological disorders. However, the cost and infrastructure requirements of these tools have limited their availability. To address this challenge, researchers and clinicians are developing new tools that are non-invasive, portable, and inexpensive. In this review article, researchers discuss the use of functional near-infrared spectroscopy (fNIRS)—a non-invasive, portable tool that uses blood oxygenation to view the brain—in patients with UCD and PKU. Authors consider the ability of fNIRS to obtain biomarkers for screening and monitoring these diseases.
Izem R, McCarter R. Randomized and non-randomized designs for causal inference with longitudinal data in rare disorders. Orphanet J Rare Dis. 2021 Nov 23;16(1):491. doi: 10.1186/s13023-021-02124-5. PMID: 34814939; PMCID: PMC8609847.
Lerner S, Eilam R, Adler L, Baruteau J, Kreiser T, Tsoory M, Brandis A, Mehlman T, Ryten M, Botia JA, Ruiz SG, Garcia AC, Dionisi-Vici C, Ranucci G, Spada M, Mazkereth R, McCarter R, Izem R, Balmat TJ, Richesson R; Members of the UCDC, Gazit E, Nagamani SCS, Erez A. ASL expression in ALDH1A1+ neurons in the substantia nigra metabolically contributes to neurodegenerative phenotype. Hum Genet. 2021 Oct;140(10):1471-1485. doi: 10.1007/s00439-021-02345-5. Epub 2021 Aug 21.
In the liver, the enzymes argininosuccinate lyase (ASL) and argininosuccinate synthase 1 (ASS1) are required to convert waste-nitrogen to urea. Loss of activity for either enzyme causes argininosuccinate lyase deficiency and citrullinemia type 1, respectively. These two disorders are a subset of the classical inborn errors of metabolism called urea cycle disorders (UCD), characterized by episodes of hyperammonemia. ASL deficiency can also result in impaired nitric oxide (NO) synthesis, decreased tyrosine hydroxylase (TH) activity, and low dopamine and norepinephrine levels in the neuronal cells. Both dopamine and norepinephrine are important neurotransmitters, and their deficiency has been associated with neurodegenerative disorders, including Parkinson's Disease. In this study, researchers used a mouse model with loss of ASL in catecholamine neurons to test the hypothesis that decreased activity of ASL and TH would contribute to neurodegeneration. They found that neuronal loss of ASL results in catecholamine deficiency, in accumulation and formation of tyrosine aggregates, in elevation of α-synuclein, and phenotypically in motor and cognitive deficits. Study authors say their data point to a potential metabolic link between accumulations of tyrosine and seeding of pathological aggregates in neurons as initiators for the pathological processes involved in neurodegeneration. They suggest that regulating NO levels may be beneficial for the treatment of catecholamine-related neurodegenerative disorders.
Liu N, Xiao J, Gijavanekar C, Pappan KL, Glinton KE, Shayota BJ, Kennedy AD, Sun Q, Sutton VR, Elsea SH. Comparison of Untargeted Metabolomic Profiling vs Traditional Metabolic Screening to Identify Inborn Errors of Metabolism. JAMA Netw Open. 2021 Jul 1;4(7):e2114155. doi: 10.1001/jamanetworkopen.2021.14155.
Sen K, Anderson AA, Whitehead MT, Gropman AL. Review of Multi-Modal Imaging in Urea Cycle Disorders: The Old, the New, the Borrowed, and the Blue. Front Neurol. 2021 Apr 28;12:632307. doi: 10.3389/fneur.2021.632307. eCollection 2021.
Nagamani SCS, Ali S, Izem R, Schady D, Masand P, Shneider BL, Leung DH, Burrage LC. Biomarkers for liver disease in urea cycle disorders. Mol Genet Metab. 2021 Apr 8:S1096-7192(21)00685-5. doi: 10.1016/j.ymgme.2021.04.001. Online ahead of print.
Stergachis AB, Krier JB, Merugumala SK, Berry GT, Lin AP. Clinical utility of brain MRS imaging of patients with adult-onset non-cirrhotic hyperammonemia. Mol Genet Metab Rep. 2021 Mar 13;27:100742. doi: 10.1016/j.ymgmr.2021.100742. eCollection 2021 Jun.
Sen K, Castillo Pinto C, Gropman AL. Expanding Role of Proton Magnetic Resonance Spectroscopy: Timely Diagnosis and Treatment Initiation in Partial Ornithine Transcarbamylase Deficiency. J Pediatr Genet. 2021 Mar;10(1):77-80. doi: 10.1055/s-0040-1709670. Epub 2020 Apr 23.
McGowan M, Ferreira C, Whitehead M, Basu SK, Chang T, Gropman A. The Application of Neurodiagnostic Studies to Inform the Acute Management of a Newborn Presenting With Sarbamoyl Shosphate Synthetase 1 Deficiency. Child Neurol Open. 2021 Jan 22;8:2329048X20985179. doi: 10.1177/2329048X20985179. eCollection 2021 Jan-Dec.
Sen K, Whitehead M, Castillo Pinto C, Caldovic L, Gropman A. Fifteen years of urea cycle disorders brain research: Looking back, looking forward. Anal Biochem. 2022 Jan 1;636:114343. doi: 10.1016/j.ab.2021.114343. Epub 2021 Oct 9. PMID: 34637785; PMCID: PMC8671367.
Posset R, Kölker S, Gleich F, Okun JG, Gropman AL, Nagamani SCS, Scharre S, Probst J, Walter ME, Hoffmann GF, Garbade SF, Zielonka M; Urea Cycle Disorders Consortium (UCDC) and the European registry and network for Intoxication type Metabolic Diseases (E-IMD) consortia study group. Severity-adjusted evaluation of newborn screening on the metabolic disease course in individuals with cytosolic urea cycle disorders. Mol Genet Metab. 2020 Dec;131(4):390-397. doi: 10.1016/j.ymgme.2020.10.013. Epub 2020 Nov 7.
Anderson AA, Gropman A, Le Mons C, Stratakis CA, Gandjbakhche AH. Hemodynamics of Prefrontal Cortex in Ornithine Transcarbamylase Deficiency: A Twin Case Study. Front Neurol. 2020 Aug 14;11:809. doi: 10.3389/fneur.2020.00809. PMID: 32922350; PMCID: PMC7456944.
Sen K, Whitehead MT, Gropman AL. Multimodal imaging in urea cycle-related neurological disease - What can imaging after hyperammonemia teach us. Transl Sci Rare Dis. 2020 Aug 3;5(1-2):87-95. doi: 10.3233/TRD-200048.
Posset R, Garbade SF, Gleich F, Gropman AL, de Lonlay P, Hoffmann GF, Garcia-Cazorla A, Nagamani SCS, Baumgartner MR, Schulze A, Dobbelaere D, Yudkoff M, Kölker S, Zielonka M; Urea Cycle Disorders Consortium (UCDC); European registry and network for Intoxication type Metabolic Diseases (E-IMD). Long-term effects of medical management on growth and weight in individuals with urea cycle disorders. Sci Rep. 2020 Jul 20;10(1):11948. doi: 10.1038/s41598-020-67496-3.
Imagawa E, Diaz GA, Oishi K. A novel Romani microdeletion variant in the promoter sequence of ASS1 causes citrullinemia type I. Imagawa E. 2020 Jun 29;24:100619. doi: 10.1016/j.ymgmr.2020.100619. PMID: 32637322; PMCID: PMC7330059.
Zielonka M, Garbade SF, Gleich F, Okun JG, Nagamani SCS, Gropman AL, Hoffmann GF, Kölker S, Posset R; Urea Cycle Disorders Consortium (UCDC) and the European registry and network for Intoxication type Metabolic Diseases (E-IMD) Consortia Study Group. From genotype to phenotype: Early prediction of disease severity in argininosuccinic aciduria. Hum Mutat. 2020 May;41(5):946-960. doi: 10.1002/humu.23983. Epub 2020 Jan 30.
Barkovich E, Gropman AL. Late Onset Ornithine Transcarbamylase Deficiency Triggered by an Acute Increase in Protein Intake: A Review of 10 Cases Reported in the Literature. Case Rep Genet. 2020 Apr 25;2020:7024735. doi: 10.1155/2020/7024735. PMID: 32373372; PMCID: PMC7197010.
Rech ME, McCarthy JM, Chen CA, Edmond JC, Shah VS, Bosch DGM, Berry GT, Williams L, Madan-Khetarpal S, Niyazov D, Shaw-Smith C, Kovar EM, Lupo PJ, Schaaf CP. Phenotypic expansion of Bosch-Boonstra-Schaaf optic atrophy syndrome and further evidence for genotype-phenotype correlations. Am J Med Genet A. 2020 Apr 10. doi: 10.1002/ajmg.a.61580. PMID: 32275123.
Anderson A, Gropman A, Le Mons C, Stratakis C, Gandjbakhche A. Evaluation of neurocognitive function of prefrontal cortex in ornithine transcarbamylase deficiency. Mol Genet Metab. 2020 Mar;129(3):207-212. doi: 10.1016/j.ymgme.2019.12.014. Epub 2020 Jan 10. PMID: 31952925. Full Text.
Burrage LC, Madan S, Li X, Ali S, Mohammad M, Stroup BM, Jiang MM, Cela R, Bertin T, Jin Z, Dai J, Guffey D, Finegold M; Members of the Urea Cycle Disorders Consortium (UCDC), Nagamani S, Minard CG, Marini J, Masand P, Schady D, Shneider BL, Leung DH, Bali D, Lee B. Chronic liver disease and impaired hepatic glycogen metabolism in argininosuccinate lyase deficiency. JCI Insight. 2020 Feb 27;5(4):e132342. doi: 10.1172/jci.insight.132342.
Berry SA, Coughlin CR 2nd, McCandless S, McCarter R, Seminara J, Yudkoff M, LeMons C. Developing interactions with industry in rare diseases: lessons learned and continuing challenges. Genet Med. 2020 Jan;22(1):219-226. doi: 10.1038/s41436-019-0616-9. Epub 2019 Jul 24.
Gropman AL, Anderson A. Novel imaging technologies for genetic diagnoses in the inborn errors of metabolism. J Transl Genet Genom. 2020;4:429-445. doi: 10.20517/jtgg.2020.09. Epub 2020 Nov 13.
Lerner S, Anderzhanova E, Verbitsky S, Eilam R, Kuperman Y, Tsoory M, Kuznetsov Y, Brandis A, Mehlman T, Mazkereth R; UCDC Neuropsychologists, McCarter R, Segal M, Nagamani SCS, Chen A, Erez A. ASL Metabolically Regulates Tyrosine Hydroxylase in the Nucleus Locus Coeruleus. Cell Rep. 2019 Nov 19;29(8):2144-2153.e7. doi: 10.1016/j.celrep.2019.10.043.
Liu XB, Haney JR, Cantero G, Lambert JR, Otero-Garcia M, Truong B, Gropman A, Cobos I, Cederbaum SD, Lipshutz GS. Hepatic arginase deficiency fosters dysmyelination during postnatal CNS development. JCI Insight. 2019 Sep 5;4(17):e130260. doi: 10.1172/jci.insight.130260.
Zielonka M, Kölker S, Gleich F, Stützenberger N, Nagamani SCS, Gropman AL, Hoffmann GF, Garbade SF, Posset R; Urea Cycle Disorders Consortium (UCDC) and the European Registry and Network for Intoxication type Metabolic Diseases (E-IMD) Consortia Study Group. Early prediction of phenotypic severity in Citrullinemia Type 1. Ann Clin Transl Neurol. 2019 Sep;6(9):1858-1871. doi: 10.1002/acn3.50886. Epub 2019 Aug 30.
Burrage LC, Thistlethwaite L, Stroup BM, Sun Q, Miller MJ, Nagamani SCS, Craigen W, Scaglia F, Sutton VR, Graham B, Kennedy AD; Members of the UCDC,, Milosavljevic A, Lee BH, Elsea SH. Untargeted metabolomic profiling reveals multiple pathway perturbations and new clinical biomarkers in urea cycle disorders. Genet Med. 2019 Sep;21(9):1977-1986. doi: 10.1038/s41436-019-0442-0. Epub 2019 Jan 23.
Diaz GA, Schulze A, Longo N, Rhead W, Feigenbaum A, Wong D, Merritt JL 2nd, Berquist W, Gallagher RC, Bartholomew D, McCandless SE, Smith WE, Harding CO, Zori R, Lichter-Konecki U, Vockley J, Canavan C, Vescio T, Holt RJ, Berry SA. Long-term safety and efficacy of glycerol phenylbutyrate for the management of urea cycle disorder patients. Mol Genet Metab. 2019 Jul 10. pii: S1096-7192(19)30323-3. PMID: 31326288. Full Text.
Waisbren SE, Stefanatos AK, Kok TMY, Ozturk-Hismi B. Neuropsychological attributes of urea cycle disorders: A systematic review of the literature. J Inherit Metab Dis. 2019 Jul 3. PMID: 31268178, Full Text.
Posset R, Gropman AL, Nagamani SCS, Burrage LC, Bedoyan JK, Wong D, Berry GT, Baumgartner MR, Yudkoff M, Zielonka M, Hoffmann GF, Burgard P, Schulze A, McCandless SE, Garcia-Cazorla A, Seminara J, Garbade SF, Kölker S; Urea Cycle Disorders Consortium and the European Registry and Network for Intoxication Type Metabolic Diseases Consortia Study Group. Impact of Diagnosis and Therapy on Cognitive Function in Urea Cycle Disorders. Ann Neurol. 2019 Jul;86(1):116-128. doi: 10.1002/ana.25492. Epub 2019 May 13.
Uittenbogaard M, Brantner CA, Fang Z, Wong LJ, Gropman A, Chiaramello A. The m.11778 A > G variant associated with the coexistence of Leber's hereditary optic neuropathy and multiple sclerosis-like illness dysregulates the metabolic interplay between mitochondrial oxidative phosphorylation and glycolysis. Mitochondrion. 2019 May;46:187-194. doi: 10.1016/j.mito.2018.06.001. Epub 2018 Jun 8.
Buerger C, Garbade SF, Dietrich Alber F, Waisbren SE, McCarter R, Kölker S, Burgard P; Urea Cycle Disorders Consortium. Impairment of cognitive function in ornithine transcarbamylase deficiency is global rather than domain-specific and is associated with disease onset, sex, maximum ammonium, and number of hyperammonemic events. J Inherit Metab Dis. 2019 Mar;42(2):243-253. doi: 10.1002/jimd.12013. Epub 2019 Jan 22.
Posset R, Garbade SF, Boy N, Burlina AB, Dionisi-Vici C, Dobbelaere D, Garcia-Cazorla A, de Lonlay P, Teles EL, Vara R, Mew NA, Batshaw ML, Baumgartner MR, McCandless SE, Seminara J, Summar M, Hoffmann GF, Kölker S, Burgard P; Additional individual contributors of the UCDC and the E-IMD consortium. Transatlantic combined and comparative data analysis of 1095 patients with urea cycle disorders-A successful strategy for clinical research of rare diseases. J Inherit Metab Dis. 2019 Jan;42(1):93-106. doi: 10.1002/jimd.12031.
Ah Mew N, Cnaan A, McCarter R, Choi H, Glass P, Rice K, Scavo L, Gillespie CW, Diaz GA, Berry GT, Wong D, Konczal L, McCandless SE, Coughlin CR, II, Weisfeld-Adams JD, Ficicioglu C, Yudkoff M, Enns GM, Lichter-Konecki U, Gallagher R, Tuchman M. Conducting an investigator-initiated randomized double-blinded intervention trial in acute decompensation of inborn errors of metabolism: Lessons from the N-Carbamylglutamate Consortium. Transl Sci Rare Dis. 2018 Dec 20;3(3-4):157-170. doi: 10.3233/TRD-180031. PMID: 30613471; PMCID: PMC6311376.
Wiwattanadittakul N, Prust M, Gaillard WD, Massaro A, Vezina G, Tsuchida TN, Gropman AL. The utility of EEG monitoring in neonates with hyperammonemia due to inborn errors of metabolism. Mol Genet Metab. 2018 Nov;125(3):235-240. doi: 10.1016/j.ymgme.2018.08.011. Epub 2018 Aug 24.
Uittenbogaard M, Gropman A, Brantner CA, Chiaramello A. Novel metabolic signatures of compound heterozygous Szt2 variants in a case of early-onset of epileptic encephalopathy. Clin Case Rep. 2018 Oct 25;6(12):2376-2384. doi: 10.1002/ccr3.1868. eCollection 2018 Dec.
Kho J, Tian X, Wong WT, Bertin T, Jiang MM, Chen S, Jin Z, Shchelochkov OA, Burrage LC, Reddy AK, Jiang H, Abo-Zahrah R, Ma S, Zhang P, Bissig KD, Kim JJ, Devaraj S, Rodney GG, Erez A, Bryan NS, Nagamani SCS, Lee BH. Argininosuccinate Lyase Deficiency Causes an Endothelial-Dependent Form of Hypertension. Am J Hum Genet. 2018 Aug 2;103(2):276-287. doi: 10.1016/j.ajhg.2018.07.008.
Posset R, Garbade SF, Boy N, Burlina AB, Dionisi-Vici C, Dobbelaere D, Garcia-Cazorla A, de Lonlay P, Teles EL, Vara R, Ah Mew N, Batshaw ML, Baumgartner MR, McCandless SE, Seminara J, Summar ML, Hoffmann GF, Kölker S, Burgard P; on behalf of the UCDC and the E-IMD consortium. Transatlantic combined and comparative data analysis of 1095 patients with urea cycle disorders – a successful strategy for clinical research of rare diseases. J Inherit Metab Dis. 2018 Jul 4. PMID: 29974348.
The Urea Cycle Disorders Consortium (UCDC) and the European Registry and Network for Intoxication Type Metabolic Disorders (E-IMD) collaborated to compare the prevalence and characteristics of urea cycle disorders (UCDs) in North America and Europe. The UCDC Longitudinal Study data was used for North America. Combining registries from both consortia, researchers looked at the medical histories of over 1,000 patients with UCD for information such as UCD type, late disease onset (clinical symptoms at more than 28 days old) or early dis-ease onset (clinical symptoms at 28 days old or less), and age of diagnosis. In North America and Europe, Ornithine Transcarbamylase Deficiency (OTCD ) and late disease onset were the most common; however, the lack of early onset reports may have been caused by the voluntary nature of the registries, as the severe symptoms associated with early onset UCDs could make participation more difficult. The data also showed that the delay between age of clinical symptoms and age of diagnosis was shorter for early onset patients, which was likely due to the higher visibility of symptoms such as seizures.
Nagamani SCS, Agarwal U, Tam A, Azamian M, McMeans A, Didelija IC, Mohammad MA, Marini JC. A randomized trial to study the comparative efficacy of phenylbutyrate and benzoate on nitrogen excretion and ureagenesis in healthy volunteers. Genet Med. 2018 Jul;20(7):708-716. doi: 10.1038/gim.2017.167. Epub 2017 Oct 12.
Waisbren SE, Cuthbertson D, Burgard P, Holbert A, McCarter R, Cederbaum S; Members of the Urea Cycle Disorders Consortium. Biochemical markers and neuropsychological functioning in distal urea cycle disorders. J Inherit Metab Dis. 2018 Jul;41(4):657-667. doi: 10.1007/s10545-017-0132-5. Epub 2018 Feb 8.
Merritt JL 2nd, Brody LL, Pino G, Rinaldo P. Newborn screening for proximal urea cycle disorders: Current evidence supporting recommendations for newborn screening. Mol Genet Metab. 2018 Jun;124(2):109-113. doi: 10.1016/j.ymgme.2018.04.006. Epub 2018 Apr 20. PubMed PMID: 29703588.
Uittenbogaard M, Brantner CA, Fang Z, Wong LC, Gropman A, Chiaramello A. Novel insights into the functional metabolic impact of an apparent de novo m.8993T>G variant in the MT-ATP6 gene associated with maternally inherited form of Leigh Syndrome. Mol Genet Metab. 2018 May;124(1):71-81. doi: 10.1016/j.ymgme.2018.03.011. Epub 2018 Mar 27.
Uittenbogaard M, Brantner CA, Chiaramello A. Epigenetic modifiers promote mitochondrial biogenesis and oxidative metabolism leading to enhanced differentiation of neuroprogenitor cells. Cell Death Dis. 2018 Mar 2;9(3):360. doi: 10.1038/s41419-018-0396-1.
Sin YY, Ballantyne LL, Richmond CR, Funk CD. Transplantation of Gene-Edited Hepatocyte-like Cells Modestly Improves Survival of Arginase-1-Deficient Mice. Mol Ther Nucleic Acids. 2018 Mar 2;10:122-130. doi: 10.1016/j.omtn.2017.11.012. Epub 2017 Dec 1.
Jichlinski A, Clarke L, Whitehead MT, Gropman A. "Cerebral palsy" in a patient with arginase deficiency. Semin Pediatr Neurol. 2018;26:110-114. Full Text.
Meyburg J, Opladen T, Spiekerkötter U, Schlune A, Schenk JP, Schmidt J, Weitz J, Okun J, Bürger F, Omran TB, Abdoh G, Al Rifai H, Monavari A, Konstantopoulou V, Kölker S, Yudkoff M, Hoffmann GF. Human heterologous liver cells transiently improve hyperammonemia and ureagenesis in individuals with severe urea cycle disorders. J Inherit Metab Dis. 2018;41:81-90. PMID: 29027067.
*Lindsay C, Burrage, Brendan Lee, and Sandesh C, S Nagamani. Urea Cycle Disorders. Rudolph Pediatrics, Chapter 141, p 23rd Edition, McGraw Hill. 2018
Schrier Vergano SA, Le Mons C. Hyperammonemia in Neonates: Looking beyond sepsis. Neonatology Today. 2017 Dec, Vol 13/Issue 12, pp 15-16. Online Full Text.
Sin YY, Price PR, Ballantyne LL, Funk CD. Proof-of-Concept Gene Editing for the Murine Model of Inducible Arginase-1 Deficiency. Sci Rep. 2017 May 31;7(1):2585. doi: 10.1038/s41598-017-02927-2.
Shi D, Zhao G, Ah Mew N, Tuchman M. Precision medicine in rare disease: Mechanisms of disparate effects of N-carbamyl-l-glutamate on mutant CPS1 enzymes. Mol Genet Metab. 2017 Mar;120(3):198–206. PMID: 28007335, PMCID: PMC5346444.
Longo N , Holt RJ. Glycerol phenylbutyrate for the maintenance treatment of patients with deficiencies in enzymes of the urea cycle. Expert Opin. on Orphan Drugs. 5 (12) (2017), pp. 999-1010. Full Text.
Nettesheim S, Kölker S, Karall D, Häberle J, Posset R, Hoffmann GF, Heinrich B, Gleich F, Garbade SF; Arbeitsgemeinschaft für Pädiatrische Stoffwechselstörungen (APS); European registry and network for Intoxication type Metabolic Diseases (E-IMD); Erhebungseinheit für Seltene Pädiatrische Erkrankungen in Deutschland (ESPED); Austrian Metabolic Group; Swiss Paediatric Surveillance Unit (SPSU). Incidence, disease onset and short-term outcome in urea cycle disorders -cross-border surveillance in Germany, Austria and Switzerland. Orphanet J Rare Dis. 2017;12:111. PMID: 28619060, PMCID: PMC5472961.
Berry SA, Longo N, Diaz GA, McCandless SE, Smith WE, Harding CO, Zori R, Ficicioglu C, Lichter-Konecki U, Robinson B, Vockley J. Safety and efficacy of glycerol phenylbutyrate for management of urea cycle disorders in patients aged 2 months to 2 years. Mol Genet Metab. 2017;122(3):46-53. PMID: 28916119, Full Text.
Butler MG, Lee J, Cox DM, Manzardo AM, Gold JA, Miller JL, Roof E, Dykens E, Kimonis V, Driscoll DJ. Growth Charts for Prader-Willi Syndrome During Growth Hormone Treatment. Clin Pediatr (Phila). 2016 Sep;55(10):957-74. doi: 10.1177/0009922815617973. Epub 2016 Feb 3.
Shchelochkov OA ,Dickinson K , Scharschmidt BF , Lee B, Marino M, Le Mons C. Barriers to drug adherence in the treatment of urea cycle disorders: assessment of patient, caregiver and provider perspectives. Mol Genet Metab Rep. 2016 Jul 20:8:43-7. doi: 10.1016/j.ymgmr.2016.07.003. eCollection 2016 Sep.
Waisbren SE, Gropman AL; Members of the Urea Cycle Disorders Consortium (UCDC), Batshaw ML. Improving long term outcomes in urea cycle disorders-report from the Urea Cycle Disorders Consortium. J Inherit Metab Dis. 2016 Jul;39(4):573-84. doi: 10.1007/s10545-016-9942-0. Epub 2016 May 23.
Atwal PS, Medina CR, Burrage LC, Sutton VR. Nineteen-year follow-up of a patient with severe glutathione synthetase deficiency. J Hum Genet. 2016 Jul;61(7):669-72. doi: 10.1038/jhg.2016.20. Epub 2016 Mar 17.
Shapiro E, Bernstein J, Adams HR, Barbier AJ, Buracchio T, Como P, Delaney KA, Eichler F, Goldsmith JC, Hogan M, Kovacs S, Mink JW, Odenkirchen J, Parisi MA, Skrinar A, Waisbren SE, Mulberg AE. Neurocognitive clinical outcome assessments for inborn errors of metabolism and other rare conditions. Mol Genet Metab. 2016 Jun;118(2):65-9. doi: 10.1016/j.ymgme.2016.04.006. Epub 2016 Apr 14.
Merkel PA, Manion M, Gopal-Srivastava R, Groft S, Jinnah HA, Robertson D, Krischer JP; Rare Diseases Clinical Research Network. The partnership of patient advocacy groups and clinical investigators in the rare diseases clinical research network. Orphanet J Rare Dis. 2016 May 18;11(1):66. doi: 10.1186/s13023-016-0445-8.
Laemmle A, Gallagher RC, Keogh A, Stricker T, Gautschi M, Nuoffer JM, Baumgartner MR, Häberle J. Frequency and Pathophysiology of Acute Liver Failure in Ornithine Transcarbamylase Deficiency (OTCD). PLoS One. 2016 Apr 12;11(4):e0153358. doi: 10.1371/journal.pone.0153358. eCollection 2016.
Burrage LC, Miller MJ, Wong LJ, Kennedy AD, Sutton VR, Sun Q, Elsea SH, Graham BH. Elevations of C14:1 and C14:2 Plasma Acylcarnitines in Fasted Children: A Diagnostic Dilemma. J Pediatr. 2016 Feb;169:208-13.e2. doi: 10.1016/j.jpeds.2015.10.045. Epub 2015 Nov 18.
Lee B, Diaz GA, Rhead W, Lichter-Konecki U, Feigenbaum A, Berry SA, Le Mons C, Bartley J, Longo N, Nagamani SC, Berquist W, Gallagher RC, Harding CO, McCandless SE, Smith W, Schulze A, Marino M, Rowell R, Coakley DF, Mokhtarani M, Scharschmidt BF. Glutamine and hyperammonemic crises in patients with urea cycle disorders. Mol Genet Metab. 2016 Jan;117(1):27-32. doi: 10.1016/j.ymgme.2015.11.005. Epub 2015 Nov 11.
Opladen T, Lindner M, Das AM, Marquardt T, Khan A, Emre SH, Burton BK, Barshop BA, Böhm T, Meyburg J, Zangerl K, Mayorandan S, Burgard P, Dürr UH, Rosenkranz B, Rennecke J, Derbinski J, Yudkoff M, Hoffmann GF. In vivo monitoring of urea cycle activity with (13)C-acetate as a tracer of ureagenesis. Mol Genet Metab. 2016 Jan;117(1):19-26. doi: 10.1016/j.ymgme.2015.11.007. Epub 2015 Nov 14.
Posset R, Garcia-Cazorla A, Valayannopoulos V, Teles EL, Dionisi-Vici C, Brassier A, Burlina AB, Burgard P, Cortès-Saladelafont E, Dobbelaere D, Couce ML, Sykut-Cegielska J, Häberle J, Lund AM, Chakrapani A, Schiff M, Walter JH, Zeman J, Vara R, Kölker S, additional individual contributors of the E-IMD consortium. Age at disease onset and peak ammonium level rather than interventional variables predict the neurological outcome in urea cycle disorders. J Inherit Metab Dis. 2016;39:661-672. PMID: 27106216.
Jamiolkowski D, Kölker S, Glahn EM, Barić I, Zeman J, Baumgartner MR, Mühlhausen C, Garcia-Cazorla A, Gleich F, Haege G, Burgard P; E-IMD consortium. Behavioural and emotional problems, intellectual impairment and health-related quality of life in patients with organic acidurias and urea cycle disorders. J Inherit Metab Dis. 2016; 39: 231-41. PMID: 26310964.
Barkovich E, Robinson C, Gropman A. Brain biomarkers and neuroimaging to diagnose urea cycle disorders and assess prognosis. Expert Opinion on Orphan Drugs. 4:11, 1123-1132. Abstract.
Krivitzky LS, Walsh KS, Fisher EL, Berl MM. Executive functioning profiles from the BRIEF across pediatric medical disorders: Age and diagnosis factors. Child Neuropsychol. 2016;22(7):870-88. doi: 10.1080/09297049.2015.1054272. Epub 2015 Jul 6.
Burgard P, Kölker S, Haege G, Lindner M, Hoffmann GF. Neonatal mortality and outcome at the end of the first year of life in early onset urea cycle disorders - review and meta-analysis of observational studies published over more than 35 years. J Inherit Metab Dis. 2016;39:219-29. PMID: 26634836.
Heringer J, Valayannopoulos V, Lund AM, Wijburg FA, Freisinger P, Barić I, Baumgartner MR, Burgard P, Burlina AB, Chapman KA, I Saladelafont EC, Karall D, Mühlhausen C, Riches V, Schiff M, Sykut-Cegielska J, Walter JH, Zeman J, Chabrol B, Kölker S, additional individual contributors of the E-IMD consortium. Impact of age at onset and newborn screening on outcome in organic acidurias. J Inherit Metab Dis. 2015 Dec 21. PMID: 26689403, Full Text (with PubMed access).
Burrage LC, Charng WL, Eldomery MK, Willer JR, Davis EE, Lugtenberg D, Zhu W, Leduc MS, Akdemir ZC, Azamian M, Zapata G, Hernandez PP, Schoots J, de Munnik SA, Roepman R, Pearring JN, Jhangiani S, Katsanis N, Vissers LE, Brunner HG, Beaudet AL, Rosenfeld JA, Muzny DM, Gibbs RA, Eng CM, Xia F, Lalani SR, Lupski JR, Bongers EM, Yang Y. De Novo GMNN Mutations Cause Autosomal-Dominant Primordial Dwarfism Associated with Meier-Gorlin Syndrome. Am J Hum Genet. 2015 Dec 3;97(6):904-13. doi: 10.1016/j.ajhg.2015.11.006.
*Sin YY, Baron G, Schulze A, Funk CD. Arginase-1 deficiency. J Mol Med (Berl). 2015 Dec;93(12):1287-96. PMID: 26467175.
Burrage LC, Sun Q, Elsea SH, Jiang MM, Nagamani SC, Frankel AE, Stone E, Alters SE, Johnson DE, Rowlinson SW, Georgiou G; Members of Urea Cycle Disorders Consortium, Lee BH. Human recombinant arginase enzyme reduces plasma arginine in mouse models of arginase deficiency. Hum Mol Genet. 2015 Nov 15;24(22):6417-27. doi: 10.1093/hmg/ddv352. Epub 2015 Sep 10.
Miller MJ, Burrage LC, Gibson JB, Strenk ME, Lose EJ, Bick DP, Elsea SH, Sutton VR, Sun Q, Graham BH, Craigen WJ, Zhang VW, Wong LJ. Recurrent ACADVL molecular findings in individuals with a positive newborn screen for very long chain acyl-coA dehydrogenase (VLCAD) deficiency in the United States. Mol Genet Metab. 2015 Nov;116(3):139-45. doi: 10.1016/j.ymgme.2015.08.011. Epub 2015 Sep 2.
Kolker S, Garcia-Cazorla A, Valayannopoulos V, Lund AM, Burlina AB, Sykut-Cegielska J, Wijburg FA, Teles EL, Zeman J, Dionisi-Vici C, Barić I, Karall D, Augoustides-Savvopoulou P, Aksglaede L, Arnoux JB, Avram P, Baumgartner MR, Blasco-Alonso J, Chabrol B, Chakrapani A, Chapman K, I Saladelafont EC, Couce ML, de Meirleir L, Dobbelaere D, Dvorakova V, Furlan F, Gleich F, Gradowska W, Grünewald S, Jalan A, Häberle J, Haege G, Lachmann R, Laemmle A, Langereis E, de Lonlay P, Martinelli D, Matsumoto S, Mühlhausen C, de Baulny HO, Ortez C, Peña-Quintana L, Ramadža DP, Rodrigues E, Scholl-Bürgi S, Sokal E, Staufner C, Summar ML, Thompson N, Vara R, Pinera IV, Walter JH, Williams M, Burgard P. The phenotypic spectrum of organic acidurias and urea cycle disorders. Part 1: the initial presentation. J Inherit Metab Dis. 2015 Nov;38(6):1041-1057. PMID: 25875215, Full Text (with PubMed access).
Kolker S, Valayannopoulos V, Burlina AB, Sykut-Cegielska, Wijburg FA, Teles EL, Zeman J, Dionisi-Vici C, Barić I, Karall D, Arnoux JB, Avram P, Baumgartner MR, Blasco-Alonso J, Boy SP, Rasmussen MB, Burgard P, Chabrol B, Chakrapani A, Chapman K, Cortès I Saladelafont E, Couce ML, de Meirleir L, Dobbelaere D, Furlan F, Gleich F, González MJ, Gradowska W, Grünewald S, Honzik T, Hörster F, Ioannou H, Jalan A, Häberle J, Haege G, Langereis E, de Lonlay P, Martinelli D, Matsumoto S, Mühlhausen C, Murphy E, de Baulny HO, Ortez C, Pedrón CC, Pintos-Morell G, Pena-Quintana L, Ramadža DP, Rodrigues E, Scholl-Bürgi S, Sokal E, Summar ML, Thompson N, Vara R, Pinera IV, Walter JH, Williams M, Lund AM, Garcia-Cazorla A. The phenotypic spectrum of organic acidurias and urea cycle disorders. Part 2: the evolving clinical phenotype. J Inherit Metab Dis. 2015 Nov;38(6):1059-1074. PMID: 25875216, Full Text (with PubMed access).
Pferdehirt R, Jain M, Blazo MA, Lee B, Burrage LC. Catel-Manzke Syndrome: Further Delineation of the Phenotype Associated with Pathogenic Variants in TGDS. Mol Genet Metab Rep. 2015 Sep 1;4:89-91. doi: 10.1016/j.ymgmr.2015.08.003.
Nagamani SC, Diaz GA, Rhead W, Berry SA, Le Mons C, Lichter-Konecki U, Bartley J, Feigenbaum A, Schulze A, Longo N, Berquist W, Gallagher R, Bartholomew D, Harding CO, Korson MS, McCandless SE, Smith W, Vockley J, Kronn D, Zori R, Cederbaum S, Merritt JL 2nd, Wong D, Coakley DF, Scharschmidt BF, Dickinson K, Marino M, Lee BH, Mokhtarani M. Self-reported treatment-associated symptoms among patients with urea cycle disorders participating in glycerol phenylbutyrate clinical trials. Mol Genet Metab. 2015 Sep-Oct;116(1-2):29-34. doi: 10.1016/j.ymgme.2015.08.002. Epub 2015 Aug 5.
Shi D, Allewell NM, Tuchman M. From Genome to Structure and Back Again: A Family Portrait of the Transcarbamylases. Int J Mol Sci. 2015 Aug 12;16(8):18836-64. doi: 10.3390/ijms160818836.
Boyer SW, Barclay LJ, Burrage LC. Inherited Metabolic Disorders: Aspects of Chronic Nutrition Management. Nutr Clin Pract. 2015 Aug;30(4):502-10. doi: 10.1177/0884533615586201. Epub 2015 Jun 16.
Lee B, Diaz GA, Rhead W, Lichter-Konecki U, Feigenbaum A, Berry SA, Le Mons C, Bartley JA, Longo N, Nagamani SC, Berquist W, Gallagher R, Bartholomew D, Harding CO, Korson MS, McCandless SE, Smith W, Cederbaum S, Wong D, Merritt JL 2nd, Schulze A, Vockley J, Kronn D, Zori R, Summar M, Milikien DA, Marino M, Coakley DF, Mokhtarani M; UCD Consortium, Scharschmidt BF. Blood ammonia and glutamine as predictors of hyperammonemic crises in patients with urea cycle disorder. Genet Med. 2015 Jul;17(7):561-8. doi: 10.1038/gim.2014.148. Epub 2014 Dec 11.
Pacheco-Colón I, Washington SD, Sprouse C, Helman G, Gropman AL, VanMeter JW. Reduced Functional Connectivity of Default Mode and Set-Maintenance Networks in Ornithine Transcarbamylase Deficiency. PLoS One. 2015 Jun 11;10(6):e0129595. doi: 10.1371/journal.pone.0129595. eCollection 2015.
Shi D, Allewell NM, Tuchman M. The N-Acetylglutamate Synthase Family: Structures, Function and Mechanisms. Int J Mol Sci. 2015 Jun 9;16(6):13004-22. doi: 10.3390/ijms160613004.
Caldovic L, Abdikarim I, Narain S, Tuchman M, Morizono H. Genotype-Phenotype Correlations in Ornithine Transcarbamylase Deficiency: A Mutation Update. J Genet Genomics. 2015 May 20;42(5):181-94. doi: 10.1016/j.jgg.2015.04.003. Epub 2015 May 19.
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Chong JX, Burrage LC, Beck AE, Marvin CT, McMillin MJ, Shively KM, Harrell TM, Buckingham KJ, Bacino CA, Jain M, Alanay Y, Berry SA, Carey JC, Gibbs RA, Lee BH, Krakow D, Shendure J, Nickerson DA; University of Washington Center for Mendelian Genomics, Bamshad MJ. Autosomal-Dominant Multiple Pterygium Syndrome Is Caused by Mutations in MYH3. Am J Hum Genet. 2015 May 7;96(5):841-9. doi: 10.1016/j.ajhg.2015.04.004.
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Lichter-Konecki U, Nadkarni V, Moudgil A, Cook N, Poeschl J, Meyer MT, Dimmock D, Baumgart S. Feasibility of adjunct therapeutic hypothermia treatment for hyperammonemia and encephalopathy due to urea cycle disorders and organic acidemias. Mol Genet Metab. 2013 Aug;109(4):354-9. doi: 10.1016/j.ymgme.2013.05.014. Epub 2013 May 29.
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Monteleone JP, Mokhtarani M, Diaz GA, Rhead W, Lichter-Konecki U, Berry SA, Lemons C, Dickinson K, Coakley D, Lee B, Scharschmidt BF. Population pharmacokinetic modeling and dosing simulations of nitrogen-scavenging compounds: disposition of glycerol phenylbutyrate and sodium phenylbutyrate in adult and pediatric patients with urea cycle disorders. J Clin Pharmacol. 2013 Jul;53(7):699-710. doi: 10.1002/jcph.92. Epub 2013 Jun 15.
Diaz GA, Krivitzky LS, Mokhtarani M, Rhead W, Bartley J, Feigenbaum A, Longo N, Berquist W, Berry SA, Gallagher R, Lichter-Konecki U, Bartholomew D, Harding CO, Cederbaum S, McCandless SE, Smith W, Vockley G, Bart SA, Korson MS, Kronn D, Zori R, Merritt JL 2nd, C S Nagamani S, Mauney J, Lemons C, Dickinson K, Moors TL, Coakley DF, Scharschmidt BF, Lee B. Ammonia control and neurocognitive outcome among urea cycle disorder patients treated with glycerol phenylbutyrate. Hepatology. 2013 Jun;57(6):2171-9. doi: 10.1002/hep.26058. Epub 2013 Jan 3.
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Mitchell S, Welch-Burke T, Dumitrescu L, Lomenick JP, Murdock DG, Crawford DC, Summar M. Peptide tyrosine tyrosine levels are increased in patients with urea cycle disorders. Mol Genet Metab. 2012 May;106(1):39-42. doi: 10.1016/j.ymgme.2012.02.011. Epub 2012 Feb 22.
Wilson JM, Shchelochkov OA, Gallagher RC, Batshaw ML. Hepatocellular carcinoma in a research subject with ornithine transcarbamylase deficiency. Mol Genet Metab. 2012 Feb;105(2):263-5. doi: 10.1016/j.ymgme.2011.10.016. Epub 2011 Nov 7.
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Erez A, Nagamani SC, Shchelochkov OA, Premkumar MH, Campeau PM, Chen Y, Garg HK, Li L, Mian A, Bertin TK, Black JO, Zeng H, Tang Y, Reddy AK, Summar M, O'Brien WE, Harrison DG, Mitch WE, Marini JC, Aschner JL, Bryan NS, Lee B. Requirement of argininosuccinate lyase for systemic nitric oxide production. Nat Med. 2011 Nov 13;17(12):1619-26. doi: 10.1038/nm.2544.
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Ah Mew N, Caldovic L. N-acetylglutamate synthase deficiency: an insight into the genetics, epidemiology, pathophysiology, and treatment. Appl Clin Genet. 2011 Aug 24;4:127-35. doi: 10.2147/TACG.S12702. Print 2011.
Lichter-Konecki U, Diaz GA, Merritt JL 2nd, Feigenbaum A, Jomphe C, Marier JF, Beliveau M, Mauney J, Dickinson K, Martinez A, Mokhtarani M, Scharschmidt B, Rhead W. Ammonia control in children with urea cycle disorders (UCDs); phase 2 comparison of sodium phenylbutyrate and glycerol phenylbutyrate. Mol Genet Metab. 2011 Aug;103(4):323-9. doi: 10.1016/j.ymgme.2011.04.013. Epub 2011 May 5.
Klein CJ, Villavicencio SA, Schweitzer A, Bethepu JS, Hoffman HJ, Mirza NM. Energy prediction equations are inadequate for obese Hispanic youth. J Am Diet Assoc. 2011 Aug;111(8):1204-10. doi: 10.1016/j.jada.2011.05.010.
Nissim I, Horyn O, Nissim I, Daikhin Y, Caldovic L, Barcelona B, Cervera J, Tuchman M, Yudkoff M. Down-regulation of hepatic urea synthesis by oxypurines: xanthine and uric acid inhibit N-acetylglutamate synthase. J Biol Chem. 2011 Jun 24;286(25):22055-68. doi: 10.1074/jbc.M110.209023. Epub 2011 May 3.
Häberle J, Shchelochkov OA, Wang J, Katsonis P, Hall L, Reiss S, Eeds A, Willis A, Yadav M, Summar S; Urea Cycle Disorders Consortium, Lichtarge O, Rubio V, Wong LJ, Summar M. Molecular defects in human carbamoy phosphate synthetase I: mutational spectrum, diagnostic and protein structure considerations. Hum Mutat. 2011 Jun;32(6):579-89. doi: 10.1002/humu.21406. Epub 2011 May 5.
Marini JC, Lanpher BC, Scaglia F, O'Brien WE, Sun Q, Garlick PJ, Jahoor F, Lee B. Phenylbutyrate improves nitrogen disposal via an alternative pathway without eliciting an increase in protein breakdown and catabolism in control and ornithine transcarbamylase-deficient patients. Am J Clin Nutr. 2011 Jun;93(6):1248-54. doi: 10.3945/ajcn.110.009043. Epub 2011 Apr 13.
Morgan TM, Schlegel C, Edwards KM, Welch-Burke T, Zhu Y, Sparks R, Summar M; Urea Cycle Disorders Consortium. Vaccines are not associated with metabolic events in children with urea cycle disorders. Pediatrics. 2011 May;127(5):e1147-53. doi: 10.1542/peds.2010-1628. Epub 2011 Apr 11.
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Erez A, Shchelochkov OA, Plon SE, Scaglia F, Lee B. Insights into the pathogenesis and treatment of cancer from inborn errors of metabolism. Am J Hum Genet. 2011 Apr 8;88(4):402-21. doi: 10.1016/j.ajhg.2011.03.005.
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Erez A, Nagamani SC, Lee B. Argininosuccinate lyase deficiency-argininosuccinic aciduria and beyond. Am J Med Genet C Semin Med Genet. 2011 Feb 15;157C(1):45-53. doi: 10.1002/ajmg.c.30289. Epub 2011 Feb 10.
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Wang J, Shchelochkov OA, Zhan H, Li F, Chen LC, Brundage EK, Pursley AN, Schmitt ES, Häberle J, Wong LJ. Molecular characterization of CPS1 deletions by array CGH. Mol Genet Metab. 2011 Jan;102(1):103-6. doi: 10.1016/j.ymgme.2010.08.020. Epub 2010 Sep 19.
Vadivel A, Aschner JL, Rey-Parra GJ, Magarik J, Zeng H, Summar M, Eaton F, Thébaud B. L-citrulline attenuates arrested alveolar growth and pulmonary hypertension in oxygen-induced lung injury in newborn rats. Pediatr Res. 2010 Dec;68(6):519-25. doi: 10.1203/PDR.0b013e3181f90278.
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Gropman AL, Batshaw ML. Epigenetics, copy number variation, and other molecular mechanisms underlying neurodevelopmental disabilities: new insights and diagnostic approaches. J Dev Behav Pediatr. 2010 Sep;31(7):582-91. doi: 10.1097/DBP.0b013e3181ee384e.
Ah Mew N, McCarter R, Daikhin Y, Nissim I, Yudkoff M, Tuchman M. N-carbamylglutamate augments ureagenesis and reduces ammonia and glutamine in propionic acidemia. Pediatrics. 2010 Jul;126(1):e208-14. doi: 10.1542/peds.2010-0008. Epub 2010 Jun 21.
Lee B, Rhead W, Diaz GA, Scharschmidt BF, Mian A, Shchelochkov O, Marier JF, Beliveau M, Mauney J, Dickinson K, Martinez A, Gargosky S, Mokhtarani M, Berry SA. Phase 2 comparison of a novel ammonia scavenging agent with sodium phenylbutyrate in patients with urea cycle disorders: safety, pharmacokinetics and ammonia control. Mol Genet Metab. 2010 Jul;100(3):221-8. doi: 10.1016/j.ymgme.2010.03.014. Epub 2010 Mar 23.
Quintero-Rivera F, Deignan J, Peredo J, Grody W, Crandall B, Sims M, Cederbaum S. An exon 1 deletion in OTC identified using chromosomal microarray analyses in a mother and her two affected deceased newborns: implications for the prenatal diagnosis of ornithine transcarbamylase deficiency. Mol Genet Metab. 2010;101:413-416. PMID: 20817516, Full Text (with PubMed access).
Cunningham CK, Rudy BJ, Xu J, Bethel J, Kapogiannis BG, Ahmad S, Wilson CM, Flynn PM; Adolescent Medicine Trials Network for HIV/AIDS Interventions. Randomized trial to determine safety and immunogenicity of two strategies for hepatitis B vaccination in healthy urban adolescents in the United States. Pediatr Infect Dis J. 2010 Jun;29(6):530-4. doi: 10.1097/INF.0b013e3181d285c7.
Mehta N, Cunningham CK, Flynn P, Pepe J, Obaro S, Kapogiannis BG, Bethel J, Luzuriaga K; Adolescent Trials Network for HIV/AIDS Interventions. Impaired generation of hepatitis B virus-specific memory B cells in HIV infected individuals following vaccination. Vaccine. 2010 May 7;28(21):3672-8. doi: 10.1016/j.vaccine.2010.03.022. Epub 2010 Mar 28.
Gropman A. Brain imaging in urea cycle disorders. Mol Genet Metab. 2010;100 Suppl 1(Suppl 1):S20-30. doi: 10.1016/j.ymgme.2010.01.017. Epub 2010 Feb 13.
Oldham MS, VanMeter JW, Shattuck KF, Cederbaum SD, Gropman AL. Diffusion tensor imaging in arginase deficiency reveals damage to corticospinal tracts. Pediatr Neurol. 2010 Jan;42(1):49-52. doi: 10.1016/j.pediatrneurol.2009.07.017.
Uittenbogaard M, Baxter KK, Chiaramello A. NeuroD6 genomic signature bridging neuronal differentiation to survival via the molecular chaperone network. J Neurosci Res. 2010 Jan;88(1):33-54. doi: 10.1002/jnr.22182.
Campeau PM, Pivalizza PJ, Miller G, McBride K, Karpen S, Goss J, Lee BH. Early orthotopic liver transplantation in urea cycle defects: follow up of a developmental outcome study. Mol Genet Metab. 2010;100 Suppl 1(Suppl 1):S84-7. doi: 10.1016/j.ymgme.2010.02.012. Epub 2010 Feb 19.
Seminara J, Tuchman M, Krivitzky L, Krischer J, Lee HS, Lemons C, Baumgartner M, Cederbaum S, Diaz GA, Feigenbaum A, Gallagher RC, Harding CO, Kerr DS, Lanpher B, Lee B, Lichter-Konecki U, McCandless SE, Merritt JL, Oster-Granite ML, Seashore MR, Stricker T, Summar M, Waisbren S, Yudkoff M, Batshaw ML. Establishing a consortium for the study of rare diseases: The Urea Cycle Disorders Consortium. Mol Genet Metab. 2010;100 Suppl 1(Suppl 1):S97-105. doi: 10.1016/j.ymgme.2010.01.014. Epub 2010 Feb 10.
Deignan JL, De Deyn PP, Cederbaum SD, Fuchshuber A, Roth B, Gsell W, Marescau B. Guanidino compound levels in blood, cerebrospinal fluid, and postmortem brain material of patients with argininemia. Mol Genet Metab. 2010;100 (suppl):S31-S36. PMID: 20176499, Full Text (with PubMed access).
Yudkoff M, Ah Mew N, Daikhin Y, Horyn O, Nissim I, Nissim I, Payan I, Tuchman M. Measuring in vivo ureagenesis with stable isotopes. Mol Genet Metab. 2010;100 Suppl 1(Suppl 1):S37-41. doi: 10.1016/j.ymgme.2010.02.017. Epub 2010 Feb 26.
Caldovic L, Ah Mew N, Shi D, Morizono H, Yudkoff M, Tuchman M. N-acetylglutamate synthase: structure, function and defects. Mol Genet Metab. 2010;100 Suppl 1(Suppl 1):S13-9. doi: 10.1016/j.ymgme.2010.02.018. Epub 2010 Feb 26.
Yerys BE, Wallace GL, Sokoloff JL, Shook DA, James JD, Kenworthy L. Attention deficit/hyperactivity disorder symptoms moderate cognition and behavior in children with autism spectrum disorders. Autism Res. 2009 Dec;2(6):322-33. doi: 10.1002/aur.103.
Ah Mew N, Payan I, Daikhin Y, Nissim I, Nissim I, Tuchman M, Yudkoff M. Effects of a single dose of N-carbamylglutamate on the rate of ureagenesis. Mol Genet Metab. 2009 Dec;98(4):325-30. doi: 10.1016/j.ymgme.2009.07.010. Epub 2009 Jul 14.
Gropman AL, Sailasuta N, Harris KC, Abulseoud O, Ross BD. Ornithine transcarbamylase deficiency with persistent abnormality in cerebral glutamate metabolism in adults. Radiology. 2009 Sep;252(3):833-41. doi: 10.1148/radiol.2523081878. Epub 2009 Jun 30.
Mc Guire PJ, Parikh A, Diaz GA. Profiling of oxidative stress in patients with inborn errors of metabolism. Mol Genet Metab. 2009 Sep-Oct;98(1-2):173-180. PMID: 19604711, PMCID: PMC2915835.
Brunetti-Pierri N, Erez A, Shchelochkov O, Craigen W, Lee B. Systemic hypertension in two patients with ASL deficiency: a result of nitric oxide deficiency?. Mol Genet Metab. 2009 Sep-Oct;98(1-2):195-7. doi: 10.1016/j.ymgme.2009.06.006. Epub 2009 Jun 13.
Krivitzky L, Babikian T, Lee HS, Thomas NH, Burk-Paull KL, Batshaw ML. Intellectual, adaptive, and behavioral functioning in children with urea cycle disorders. Pediatr Res. 2009 Jul;66(1):96-101. doi: 10.1203/PDR.0b013e3181a27a16.
Venkateswaran L, Scaglia F, McLin V, Hertel P, Shchelochkov OA, Karpen S, Mahoney D Jr, Yee DL. Ornithine transcarbamylase deficiency: a possible risk factor for thrombosis. Pediatr Blood Cancer. 2009 Jul;53(1):100-2. doi: 10.1002/pbc.22016.
Neill MA, Aschner J, Barr F, Summar ML. Quantitative RT-PCR comparison of the urea and nitric oxide cycle gene transcripts in adult human tissues. Mol Genet Metab. 2009 Jun;97(2):121-7. doi: 10.1016/j.ymgme.2009.02.009. Epub 2009 Mar 3.
Richesson RL, Lee HS, Cuthbertson D, Lloyd J, Young K, Krischer JP. An automated communication system in a contact registry for persons with rare diseases: scalable tools for identifying and recruiting clinical research participants. Contemp Clin Trials. 2009 Jan;30(1):55-62. doi: 10.1016/j.cct.2008.09.002. Epub 2008 Sep 7.
Griggs RC, Batshaw M, Dunkle M, Gopal-Srivastava R, Kaye E, Krischer J, Nguyen T, Paulus K, Merkel PA; Rare Diseases Clinical Research Network. Clinical research for rare disease: opportunities, challenges, and solutions. Mol Genet Metab. 2009 Jan;96(1):20-6. doi: 10.1016/j.ymgme.2008.10.003. Epub 2008 Nov 13.
Wu X, Ghimbovschi S, Aujla PK, Rose MC, Peña MT. Expression profiling of inflammatory mediators in pediatric sinus mucosa. Arch Otolaryngol Head Neck Surg. 2009 Jan;135(1):65-72. doi: 10.1001/archoto.2008.505.
Mitchell S, Ellingson C, Coyne T, Hall L, Neill M, Christian N, Higham C, Dobrowolski SF, Tuchman M, Summar M; Urea Cycle Disorder Consortium. Genetic variation in the urea cycle: a model resource for investigating key candidate genes for common diseases. Hum Mutat. 2009 Jan;30(1):56-60. doi: 10.1002/humu.20813.
Shchelochkov OA, Li F, Geraghty MT, Gallagher RC, Van Hove JL, Lichter-Konecki U, Fernhoff PM, Copeland S, Reimschisel,T, Cederbaum S, Lee B, Chinault AC, Wong L. High-frequency detection of deletions and variable rearrangements at the ornithine transcarbamylase (OTC) locus by oligonucleotide Array CGH. Mol Genet Metab. 2009;96: 97-105. PMID: 19138872, Full Text (with PubMed access).
Sailasuta N, Robertson LW, Harris KC, Gropman AL, Allen PS, Ross BD. Clinical NOE 13C MRS for neuropsychiatric disorders of the frontal lobe. J Magn Reson. 2008 Dec;195(2):219-25. doi: 10.1016/j.jmr.2008.09.012. Epub 2008 Sep 17.
Dimmock DP, Trapane P, Feigenbaum A, Keegan CE, Thoene J, Cederbaum S, Gibson J, Gambello M, Muenzer J, Vaux K, O'Brien WO, Fang P. The role of molecular testing and enzyme analysis in the management of hypomorphic citrullinemia. Am J Med Genet A. 2008 Nov 15;146A(22):2885-90. doi: 10.1002/ajmg.a.32527. Erratum in: Am J Med Genet A. 2010 Apr;152A(4):1061. PMID: 18925679; PMCID: PMC2597641.
Patrick TB, Richesson R, Andrews JE, Folk LC. SNOMED CT coding variation and grouping for "other findings" in a longitudinal study on urea cycle disorders. AMIA Annu Symp Proc. 2008 Nov 6:2008:11-5.
Summar ML, Dobbelaere D, Brusilow S, Lee B. Diagnosis, symptoms, frequency and mortality of 260 patients with urea cycle disorders from a 21-year, multicentre study of acute hyperammonaemic episodes. Acta Paediatr. 2008 Oct;97(10):1420-5. doi: 10.1111/j.1651-2227.2008.00952.x. Epub 2008 Jul 17.
Gropman AL, Fricke ST, Seltzer RR, Hailu A, Adeyemo A, Sawyer A, van Meter J, Gaillard WD, McCarter R, Tuchman M, Batshaw M; Urea Cycle Disorders Consortium. 1H MRS identifies symptomatic and asymptomatic subjects with partial ornithine transcarbamylase deficiency. Mol Genet Metab. 2008 Sep-Oct;95(1-2):21-30. doi: 10.1016/j.ymgme.2008.06.003. Epub 2008 Jul 26.
Deardorff MA, Gaddipati H, Kaplan P, Sanchez-Lara PA, Sondheimer N, Spinner NB, Hakonarson H, Ficicioglu C, Ganesh J, Markello T, Loechelt B, Zand DJ, Yudkoff M, Lichter-Konecki U. Complex management of a patient with a contiguous Xp11.4 gene deletion involving ornithine transcarbamylase: a role for detailed molecular analysis in complex presentations of classical diseases. Mol Genet Metab. 2008 Aug;94(4):498-502. doi: 10.1016/j.ymgme.2008.04.011. Epub 2008 Jun 3.
Tuchman M, Lee B, Lichter-Konecki U, Summar ML, Yudkoff M, Cederbaum SD, Kerr DS, Diaz GA, Seashore MR, Lee HS, McCarter RJ, Krischer JP, Batshaw ML; Urea Cycle Disorders Consortium of the Rare Diseases Clinical Research Network. Cross-sectional multicenter study of patients with urea cycle disorders in the United States. Mol Genet Metab. 2008 Aug;94(4):397-402. doi: 10.1016/j.ymgme.2008.05.004. Epub 2008 Jun 17.
Tuchman M, Caldovic L, Daikhin Y, Horyn O, Nissim I, Nissim I, Korson M, Burton B, Yudkoff M. N-carbamylglutamate markedly enhances ureagenesis in N-acetylglutamate deficiency and propionic acidemia as measured by isotopic incorporation and blood biomarkers. Pediatr Res. 2008 Aug;64(2):213-7. doi: 10.1203/PDR.0b013e318179454b.
Brunetti-Pierri N, Clarke C, Mane V, Palmer DJ, Lanpher B, Sun Q, O'Brien W, Lee B. Phenotypic correction of ornithine transcarbamylase deficiency using low dose helper-dependent adenoviral vectors. J Gene Med. 2008 Aug;10(8):890-896. PMID: 18563850, PMCID: PMC2766563.
Lichter-Konecki U. Profiling of astrocyte properties in the hyperammonaemic brain: shedding new light on the pathophysiology of the brain damage in hyperammonaemia. J Inherit Metab Dis. 2008 Aug;31(4):492-502. doi: 10.1007/s10545-008-0834-9. Epub 2008 Aug 9.
Nissim I, Horyn O, Nissim I, Daikhin Y, Wehrli SL, Yudkoff M. 3-isobutylmethylxanthine inhibits hepatic urea synthesis: protection by agmatine. J Biol Chem. 2008 May 30;283(22):15063-71. doi: 10.1074/jbc.M800163200. Epub 2008 Mar 28.
Zhu Y, Wang Z, Miller DJ, Clarke R, Xuan J, Hoffman EP, Wang Y. A ground truth based comparative study on clustering of gene expression data. Front Biosci. 2008 May 1;13:3839-49. doi: 10.2741/2972.
Gropman AL, Seltzer RR, Yudkoff M, Sawyer A, VanMeter J, Fricke ST. 1H MRS allows brain phenotype differentiation in sisters with late onset ornithine transcarbamylase deficiency (OTCD) and discordant clinical presentations. Mol Genet Metab. 2008 May;94(1):52-60. doi: 10.1016/j.ymgme.2007.12.008. Epub 2008 Feb 11.
Lichter-Konecki U, Mangin JM, Gordish-Dressman H, Hoffman EP, Gallo V. Gene expression profiling of astrocytes from hyperammonemic mice reveals altered pathways for water and potassium homeostasis in vivo. Glia. 2008 Mar;56(4):365-77. doi: 10.1002/glia.20624.
*Gropman AL, Rigas A. Neurometabolic disorders: urea-cycle disorder, outcomes, development and treatment. Pediatric Health. 2008;2(6):701-713. Full Text.
Cotton RG, Auerbach AD, Beckmann JS, Blumenfeld OO, Brookes AJ, Brown AF, Carrera P, Cox DW, Gottlieb B, Greenblatt MS, Hilbert P, Lehvaslaiho H, Liang P, Marsh S, Nebert DW, Povey S, Rossetti S, Scriver CR, Summar M, Tolan DR, Verma IC, Vihinen M, den Dunnen JT. Recommendations for locusspecific databases and their curation. Hum Mutat. 2008;29(1):2-5. PMID: 18157828, PMCID: PMC2752432.
Gropman AL, Summar M, Leonard JV. Neurological implications of urea cycle disorders. J Inherit Metab Dis. 2007 Nov;30(6):865-79. doi: 10.1007/s10545-007-0709-5. Epub 2007 Nov 23.
Eeds AM, Mortlock D, Wade-Martins R, Summar ML. Assessing the functional characteristics of synonymous and nonsynonymous mutation candidates by use of large DNA constructs. Am J Hum Genet. 2007 Apr;80(4):740-50. doi: 10.1086/513287. Epub 2007 Mar 8.
Dimmock DP, Kobayashi K, Iijima M, Tabata A, Wong LJ, Lee B, Saheki T, Scaglia F. Citrin deficiency: A novel cause of failure to thrive that responds to a high protein, low carbohydrate diet. Pediatrics. 2007;119:e773-e777. PMID: 17332192, Full Text (with PubMed access).
Caldovic L, Morizono H, Tuchman M. Mutations and polymorphisms in the human N-acetylglutamate synthase gene. Hum Mutat. 2007;28:754-759. PMID: 17421020, Full Text.
*Marini JC, Lanpher B, Scaglia F, Carter S, Garlick PJ, Jahoor F, Lee B. Phenylbutyrate reduces plasma leucine concentrations without affecting the flux of leucine. FASEB Journal. 2007;21:A335. Abstract.
*Scaglia F, Lanpher B, Marini J, Lee B. Role of branched chain amino acids in patients with urea cycle disorders. In: Bachmann C, Haberle J, Leonard JV (eds). Pathophysiology and Management of Hyperammonemia. SPS Publications . 2007: p.65-75.
Dobrowolski SF, Ellingson C, Caldovic L, Tuchman M. Streamlined assessment of gene variants by high resolution melt profiling utilizing the ornithine transcarbamylase gene as a model system. Hum Mutat. 2007;28:1133-1140. PMID: 17565723.
Yudkoff M, Daikhin Y, Melø TM, Nissim I, Sonnewald U, Nissim I. The ketogenic diet and brain metabolism of amino acids: relationship to the anticonvulsant effect. Annu Rev Nutr. 2007;27:415-30. doi: 10.1146/annurev.nutr.27.061406.093722.
*EA Crombez, SD Cederbaum. Urea cycle disorders. In: Schapira AHV (ed) Neurology and Clinical Neuroscience. Mosby . 2007, chapter 110, pp1469-1476.
Eeds AM, Hall LD, Yadav M, Willis A, Summar S, Putnam A, Barr F, Summar ML. The frequent observation of evidence for nonsense-mediated decay in RNA from patients with carbamyl phosphate synthetase I deficiency. Mol Genet Metab. 2006 Sep-Oct;89(1-2):80-6. doi: 10.1016/j.ymgme.2006.04.006. Epub 2006 Jun 5.
Lanpher B, Brunetti-Pierri N, Lee B. Inborn errors of metabolism: the flux from Mendelian to complex diseases. Nat Rev Genet. 2006 Jun;7(6):449-60. doi: 10.1038/nrg1880.
Camacho JA, Mardach MR, Rioseco-Camacho N, Ruiz-Pesini E, Derbeneva O, Andrade D, Zaldivar F, Qu Y, Cederbaum SD. Clinical and functional characterization of a human ORNT1mutation (T32R) in the hyperornithinemia-hyperammonemia-homocitrullinuria (HHH) syndrome. Pediatr Res. 2006;60:423-429. PMID: 16940241, Full Text.
Yamaguchi S, Brailey LL, Morizono H, Lynch MG, Bale AE, Tuchman M. Mutations and polymorphisms in the human ornithine transcarbamylase gene. Hum Mutat. 2006;27:626-632. PMID: 11793468, Full Text.
Lee B, Singh RH, Rhead WJ, Sniderman King L, Smith W, Summar ML. Considerations in the difficult-to-manage urea cycle disorder patient. Crit Care Clin. 2005 Oct;21(4 Suppl):S19-25. doi: 10.1016/j.ccc.2005.05.001.
Sniderman King L, Singh RH, Rhead WJ, Smith W, Lee B, Summar ML. Genetic counseling issues in urea cycle disorders. Crit Care Clin. 2005 Oct;21(4 Suppl):S37-44. doi: 10.1016/j.ccc.2005.08.001.
Singh RH, Rhead WJ, Smith W, Lee B, Sniderman King L, Summar M. Nutritional management of urea cycle disorders. Crit Care Clin. 2005 Oct;21(4 Suppl):S27-35. doi: 10.1016/j.ccc.2005.08.003.
Summar ML, Barr F, Dawling S, Smith W, Lee B, Singh RH, Rhead WJ, Sniderman King L, Christman BW. Unmasked adult-onset urea cycle disorders in the critical care setting. Crit Care Clin. 2005 Oct;21(4 Suppl):S1-8. doi: 10.1016/j.ccc.2005.05.002.
Smith W, Kishnani PS, Lee B, Singh RH, Rhead WJ, Sniderman King L, Smith M, Summar M. Urea cycle disorders: clinical presentation outside the newborn period. Crit Care Clin. 2005 Oct;21(4 Suppl):S9-17. doi: 10.1016/j.ccc.2005.05.007.
Hulgan T, Haas DW, Haines JL, Ritchie MD, Robbins GK, Shafer RW, Clifford DB, Kallianpur AR, Summar M, Canter JA. Mitochondrial haplogroups and peripheral neuropathy during antiretroviral therapy: an adult AIDS clinical trials group study. AIDS. 2005 Sep 2;19(13):1341-9. doi: 10.1097/01.aids.0000180786.02930.a1.
Gropman AL. Expanding the diagnostic and research toolbox for inborn errors of metabolism: the role of magnetic resonance spectroscopy. Mol Genet Metab. 2005 Sep-Oct;86(1-2):2-9. PMID: 16276565.
Crombez EA, Cederbaum SD. Hyperargininemia due to liver arginase deficiency. Mol Genet Metab. 2005 Mar;84(3):243-51. doi: 10.1016/j.ymgme.2004.11.004. Epub 2004 Dec 19.
Ensenauer R, Tuchman M, El-Youssef M, Kotagal S, Ishitani MB, Matern D, Babovic-Vuksanovic D. Management and outcome of neonatal-onset ornithine transcarbamylase deficiency following liver transplantation at 60 days of life. Mol Genet Metab. 2005;84:363-366 PMID: 15781198, Full Text (with PubMed access).
Scaglia F, Brunetti-Pierri N, Kleppe S, Marini J, Carter S, Garlick P, Jahoor F, O'Brien W, Lee B. Clinical consequences of urea cycle enzyme deficiencies and potential links to arginine and nitric oxide metabolism. J Nutr. 2004 Oct;134(10 Suppl):2775S-2782S; discussion 2796S-2797S. doi: 10.1093/jn/134.10.2775S.
McBride KL, Miller G, Carter S, Karpen S, Goss J, Lee B. Developmental outcomes with early orthotopic liver transplantation for infants with neonatal-onset urea cycle defects and a female patient with late-onset ornithine transcarbamylase deficiency. Pediatrics. 2004 Oct;114(4):e523-6. doi: 10.1542/peds.2004-0198.
Caldovic L, Morizono H, Daikhin Y, Nissim I, McCarter RJ, Yudkoff M, Tuchman M. Restoration of ureagenesis in N-acetylglutamate synthase deficiency by N-carbamylglutamate. J Pediatr. 2004 Oct;145(4):552-4. doi: 10.1016/j.jpeds.2004.06.047.
Mian A, McCormack WM Jr, Mane V, Kleppe S, Ng P, Finegold M, O'Brien WE, Rodgers JR, Beaudet AL, Lee B. Long-term correction of ornithine transcarbamylase deficiency by WPRE-mediated overexpression using a helper-dependent adenovirus. Mol Ther. 2004 Sep;10(3):492-9. doi: 10.1016/j.ymthe.2004.05.036.
Gropman AL, Batshaw ML. Cognitive outcome in urea cycle disorders. Mol Genet Metab. 2004 Apr;81 Suppl 1:S58-62. doi: 10.1016/j.ymgme.2003.11.016.
Scaglia F, Carter S, O’Brien W, Lee B. Effect of alternative pathway therapy on branched chain amino acid metabolism in urea cycle disorder patients. Mol Genet Metab. 2004 Apr;81 Suppl 1:S79-85. doi: 10.1016/j.ymgme.2003.11.017. PMID: 15050979.
Summar ML, Hall LD, Christman B, Barr F, Smith H, Kallianpur A, Brown N, Yadav M, Willis A, Eeds A, Cermak E, Summar S, Wilson A, Arvin M, Putnam A, Wills M, Cunningham G. Environmentally determined genetic expression: clinical correlates with molecular variants of carbamyl phosphate synthetase I. Mol Genet Metab. 2004;81(Suppl 1):S12-S19. PMID: 15050969, Full Text (with PubMed access).
Rohininath T, Costello DJ, Lynch T, Monavari A, Tuchman M, Treacy EP. Fatal presentation of ornithine transcarbamylase deficiency in a 62-year-old man and family studies. J Inherit Metab Dis. 2004;27:285-288. PMID: 15243986.
Tuchman M. Hyperammonemia: are the burdens too grave? Case study. Ethics Intellect Disabil. 2004;8:1,3. PMID: 15835081.
Kasumov T, Brunengraber LL, Comte B, Puchowicz MA, Jobbins K, Thomas K, David F, Kinman R, Wehrli S, Dahms W, Kerr D, Nissim I, Brunengraber H. New secondary metabolites of phenylbutyrate in humans and rats. Drug Metab Dispos. 2004;32:10-19. PMID: 14709615, Full Text.
MacArthur RB, Altincatal A, Tuchman M. Pharmacokinetics of sodium phenylacetate and sodium benzoate following intravenous administration as both a bolus and continuous infusion to healthy adult volunteers. Mol Genet Metab. 2004;Suppl:67-73. PMID: 15050977, Full Text (with PubMed access).
Tuchman M. Urea cycle disorders workshop introduction. Mol Genet Metab. 2004;81(Suppl):3. Full Text.
Kleppe S, Mian A, Lee B. Urea Cycle Disorders. Curr Treat Options Neurol. 2003 Jul;5(4):309-319. doi: 10.1007/s11940-003-0037-5.
Takanashi JI, Barkovich AJ, Cheng SF, Weisiger K, Zlatunich CO, Mudge C, Rosenthal P, Tuchman M, Packman S. Brain MR imaging in neonatal hyperammonemic encephalopathy resulting from proximal urea cycle disorders. Am J Neuroradiol. 2003;24:1184-1187. PMID: 12812952, Full Text.
Summar ML, Hall LD, Eeds AM, Hutcheson HB, Kuo AN, Willis AS, Rubio V, Arvin MK, Schofield JP, Dawson EP. Characterization of genomic structure and polymorphisms in the human carbamyl phosphate synthetase I gene. Gene. 2003;311:51-57. PMID: 12853138, Full Text (with PubMed access).
Scaglia F, Rosenberger J, Henry J, Lee B, Reeds P. Differential utilization of systemic and enteral ammonia for urea synthesis in control subjects and carriers for ornithine transcarbamylase deficiency. Am J Clin Nutr. 2003;78:749-755. PMID: 14522733, Full Text.
Barr FE, Beverley H, VanHook K, Cermak E, Christian K, Drinkwater D, Dyer K, Raggio NT, Moore JH, Christman B, Summar M. Effect of cardiopulmonary bypass on urea cycle intermediates and nitric oxide levels after congenital heart surgery. J Pediatr. 2003;142(1):26-30. PMID: 12520250, Full Text (with PubMed access).
Caldovic L, Morizono M, Panglao M, Cheng SF, Packman S, Tuchman M. Null mutations in the Nacetylglutamate synthase gene associated with acute neonatal disease and hyperammonemia. Hum Genet. 2003;112:364-368. PMID: 12594532, Full Text (with PubMed access).