Chicago Center for Jewish Genetics Disorders - Sephardic Disorders: Glycogen Storage Disease, Type III

Sephardi Disorders

Gene: Glycogen Storage Disease, Type III is caused by mutations in the amylo-1,6-glucosidase gene, which is located at 1p21. This gene encodes for the glycogen debrancher enzyme involved in the breakdown of glycogen to glucose.

Mutations and testing: The two most common mutations, 3964delT and IVS32 A->G - 12 base pairs, account for only ~12% of mutant alleles in affected patients so far. Therefore, diagnosis usually requires measurement of enzyme activity in skin fibroblasts. Enzyme analysis on blood samples may be inaccurate and is not recommended.

Traits: Glycogen is the storage form of carbohydrate in the body and is found mainly in the liver and muscles. These stores act as back-up sources of glucose during times of fasting, and for the production of ATP in muscles during exercise. Debrancher deficiency prevents the efficient utilization of glycogen and leads to accumulation of glycogen in the liver and other tissues. Clinical symptoms are fasting hypoglycemia, growth retardation, hepatomegaly, myopathy, and cardiomegaly. Progressively severe myopathy and cardiomyopathy may begin during adolescence or during the early adult years. Clinical features are variable due to differences in tissue expression, which leads to 3 main subtypes:

IIIa patients lack debrancher enzyme activity in both muscle and liver and is found in 78% of cases
IIIb patients lack enzyme debrancher activity in the liver but not muscle and is found in 15% of cases
IIIc patients lack enzyme debrancher activity in muscle but not the liver and is rare

Treatment: Treatment is aimed at preventing hypoglycemia and reducing the breakdown of muscle protein for gluconeogenesis. This requires frequent feedings that are high in protein. Oral administration of uncooked cornstarch helps prevent fasting hypoglycemia. Patients show an increased tolerance to fasting with age.

Reviewed by Dr. Joel Charrow, Children's Memorial Hospital.
1/03

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This page last updated on January 10, 2003.