Also known as congenital disorder of glycosylation type Is
A rare, X-linked condition caused by new genetic (de novo) mutations affecting N-linked glycosylation. Symptoms manifest during infancy and include intractable seizures, extremity swelling, recurrent infections, bleeding problems, an enlarged liver, a small head, severe developmental delay, intellectual disability, and affected vision.
Symptoms
ALG13-CDG is an inherited condition that affects many parts of the body. Individuals with ALG13-CDG typically develop signs and symptoms of the condition during infancy. ALG13-CDG is an X-linked condition, so may affect males and females differently.
Affected males may have seizures, hepatomegaly, recurrent infections, increased bleeding tendency, microcephaly, nystagmus, and bilateral optic nerve atrophy. Laboratory abnormalities may include elevated liver enzymes, abnormal coagulation factor activities, and abnormal transferrin glycosylation, although it can also be normal. Those who are mildly affected may have isolated developmental delay and intellectual disability.
Affected females primarily have neurological symptoms, in particular seizures. In females, ALG13-CDG is typically caused by the same de novo genetic change, N107S. Individuals with the N107S variant are typically normal at birth, but develop early onset seizures, most typically starting as infantile spasms and subsequently developing into other mixed seizure types. Some patients develop abnormal movements. All individuals have severe developmental delays, intellectual disability, may have developmental regression and visual development is frequently affected. They may have feeding difficulties and require a G-tube. Individuals with the N107S variant typically have normal transferrin glycosylation and rarely can have abnormal coagulation profiles. There are more than 20 ALG13-CDG patients published in medical literature.
Diagnosis
Given the frequently normal glycosylation testing, diagnostic testing relies on genetic testing in blood. Individuals with ALG13-CDG have one faulty copy of the ALG13 gene, which is on the X chromosome. It is usually caused by a new genetic mutation in the affected individual and not inherited from a parent.
Treatment and Prognosis
Treatments for ALG13-CDG are primarily directed at seizure management. Most patients initially respond to ACTH, but then regain epileptic seizures which sometimes respond to medications or a ketogenic diet but can also not respond to any treatments. The rest of the treatment focuses on identifying treatable medical conditions and preventing complications (including physical therapy, occupational therapy, etc.).