Also known as congenital disorder of glycosylation type Ig
A rare, inherited condition caused by a dysfunctional enzyme that cannot add mannose to proteins or fats. Symptoms manifest during infancy or early childhood, including failure to thrive, decreased muscle tone, developmental delay, intellectual disability, seizures, skeletal abnormalities, unusual facial features, sensorineural hearing loss (hearing loss caused by damage to the inner ear or the nerve from the ear to the brain), and heart muscle weakness.
Symptoms
ALG12-CDG is a very rare inherited condition that affects multiple parts of the body. There are only 12 ALG12-CDG patients published in medical literature.
Individuals with ALG12-CDG typically develop signs and symptoms of the condition during infancy or early childhood. Affected infants may suffer from a severe multi-systemic disease, in severe cases ending in death during the neonatal or infant period.
Characteristic symptoms of ALG12-CDG are psychomotor delay, intellectual disability, microcephaly, hypotonia, facial dysmorphism and male genital hypoplasia. Another characteristic clinical feature is hypogammaglobulinemia, leading to recurrent respiratory infections. Feeding difficulties can lead to a failure to gain weight and grow slower than normal (failure to thrive). Ocular abnormalities, sensorineural hearing loss, cardiac abnormalities and skeletal dysplasias are possible.
Laboratory anomalies include hypogammaglobulinemia, coagulation abnormalities (without obvious bleeding predisposition) and in some cases recurrent hypoglycemia, decreased IGF-1 and IGF-binding protein, hypocholesterolemia and hypoalbuminemia. Liver enzymes may be elevated or normal.
Brain imaging may show several abnormalities, but can also be normal.
Individuals who are only mildly affected may present with isolated developmental delay, intellectual disability and coagulation abnormalities.
Diagnosis
The primary screening tool for ALG12-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. Measuring the activity of the deficient enzyme in blood and skin fibroblasts confirms the diagnosis. The ultimate diagnosis is genetic testing in blood. Individuals with ALG12-CDG have two faulty copies of the ALG12 gene.
Treatment and Prognosis
To date, there are no known specific treatment options for ALG12-CDG. Treatment is aimed at the management of symptoms and the prevention of complications. Some ALG12-CDG patients die within the first years of life. Mild cases, however, seem to have a good life expectancy. The oldest ALG12-CDG patient that has been described in medical literature is in his 40s.