Congenital Disorders of N-linked Glycosylation

The congenital disorders of glycosylation (CDG) are a family of anabolic diseases with variable multisystem manifestations. Most of these disorders have multisystem manifestations, in addition to a wide variety of neurologic phenotypes. The most frequent type is PMM2-CDG (phosphomannomutase deficiency), which is associated with severe cerebellar atrophy, intellectual disability, stroke-like episodes and seizures, and progressive pigmentary retinopathy and demyelinating neuropathy in classic cases. Other phenotypes have considerable overlap, and with few exceptions, are accompanied by varying systemic manifestations that may include coagulopathies, gastrointestinal disease, lipodystrophy, skeletal deformities, cardiac, renal, and eye disease. CDG should be suspected in any patient with multisystem disease and neurologic manifestations, and can be efficiently screened for in most cases using carbohydrate deficient transferrin. Enzyme analysis is clinically available for the more common disorders, and molecular diagnosis is rapidly improving for all forms of CDG. Specific therapy is available for MPI-CDG and SLC365C1-CDG.