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ATP6AP1-Congenital Disorder Of Glycosylation (ATP6AP1-CDG)

Also known as Congenital Disorder Of Glycosylation Type Iis

ATP6AP1-CDG is rare X-linked disorder affects primarily males. Currently, thirty individuals with ATP6AP1-CDG are reported in medical literature. The signs and symptoms typically develop during infancy and involve many body systems.

Symptoms

Affected individuals may have variable degree of liver dysfunction and impaired immune system (immunodeficiency) with recurrent infections. Neurological involvement include developmental delay, hearing loss, seizure and abnormal body movement (dystonia). Loose skin is common and can be detected in early infancy and usually improve with age. Gastrointestinal issues such as pancreatic insufficiency and slow weight gain (failure to thrive) have been noted. Hematological abnormalities including anemia and reduced counts of white blood cells (leukopenia) and platelet (thrombocytopenia) can occur in some ATP6AP1-CDG patients. Urinary and genital defects can present and include Inguinal hernia and abnormal opening of urethra (hypospadias). Abnormal difference in facial features (dysmorphism) and congenital heart defects are less frequent. Some patients develop diaphragmatic hernia.

Laboratory abnormalities include elevated liver enzymes, abnormal coagulation factor activities, high blood cholesterol and low levels of blood copper and/or ceruloplasmin.

Diagnosis

Common screening test relies on testing the appropriate glycosylation of common proteins (one commonly used glycoprotein is transferrin). This can be tested by different methods in blood. The ultimate diagnosis is genetic testing in blood. Individuals with ATP6AP1-CDG have one faulty copy of the ATP6AP1 gene, which is located on the X chromosome. Some affected individuals have new genetic mutation not inherited from the mothers.

Treatment and Prognosis

There are no specific treatments for ATP6AP1-CDG. Liver transplantation has been successful in several ATP6AP1-CDG patients with severe liver failure. Patients with immunological involvement are managed with regular immunoglobulin infusions. Supplementations with fat soluble vitamins is used for pancreatic insufficiency. Physical, occupational and speech therapy is recommended for patients with developmental delay. There are ATP6AP1-CDG patients who died in early infancy or childhood due to liver failure, but there are patients who have lived into adulthood. The oldest patient reported in 67 years old.