Also known as Congenital Disorder of Glycosylation Type 1c
A rare, multisystemic, inherited condition, manifesting in infancy, caused by N-linked glycosylation disruption. Symptoms include failure to thrive, hypotonia (low muscle tone), developmental delay, intellectual disability, sleep, speech, and behavioral problems, seizures, ataxia (impaired balance or coordination), temporary paralysis, vision and hearing loss, liver disease, and heart muscle weakness.
Symptoms
ALG6-CDG is a very rare inherited condition that affects multiple parts of the body. It is the second most frequent congenital disorder of glycosylation (after PMM2-CDG). There are more than 98 ALG6-CDG patients published in medical literature. Affected individuals typically develop signs and symptoms of the condition during infancy. ALG6-CDG presents with a primarily neurologic phenotype: Frequent and characteristic symptoms are speech, developmental or intellectual disability, proximal muscle weakness, and hypotonia, which causes many of the affected children to be wheelchair dependent. The majority of patients also develop epilepsy, ataxia, nystagmus, and strabismus, and some develop microcephaly. Feeding difficulties and intestinal problems (such as protein-losing enteropathy (PLE)), are common in ALG6-CDG, which may lead to a failure to gain weight and grow slower than normal (failure to thrive). Several patients show behavioral problems, including autistic behavior, depressive features, episodes of aggressive behavior, as well as sleep disturbances. While limb anomalies are commonly seen, facial dysmorphism is rather rare. Other less frequently seen symptoms include cardiomyopathy, liver disease, and visual and hearing loss.
Severely affected patients may die in early childhood from complications of PLE, sepsis, or seizures. In contrast, more mildly affected patients may only present with hypotonia and seizures, or behavioral abnormalities and speech disability.
Laboratory anomalies include coagulation abnormalities (with or without a bleeding tendency), hypoalbuminemia, hypocholesterolemia, and endocrine abnormalities. Liver enzymes may be elevated or normal. Some patients develop anemia, which is usually due to malabsorption. Hypoglycemia and hyperinsulism have been described in only a few patients.
Brain imaging may show abnormalities, such as vermis hypoplasia or brain atrophy, but may also be normal.
Diagnosis
The primary screening tool for ALG6-CDG is testing of the appropriate glycosylation of common proteins (one commonly used glycoprotein is transferrin). This can be tested by different methods in blood. The metabolic diagnosis can be confirmed by lipid linked oligosaccharide analysis in fibroblasts. The ultimate diagnosis is genetic testing in blood. Individuals with ALG6-CDG have two faulty copies of the ALG6 gene.
Treatment and Prognosis
To date, there are no known specific treatment options for ALG6-CDG. Treatment is aimed at the management of symptoms and the prevention of complications. Most diagnosed ALG6-CDG patients are still young, which makes long-term prognosis difficult. Most of the older patients reached puberty, and a few of them reached adulthood. The oldest ALG6-CDG patient that has been described in medical literature has reached her 40s.