Glycogen storage disease type 3

Glycogen debranching enzyme (GDE) deficiency, or glycogenosis type 3 (GSD-3), is a glycogen storage disease characterized by severe muscle weakness and liver disease.

The disease is caused by mutations in the AGL gene, resulting in a deficit of GDE. The GDE enzyme acts together with the enzyme glycogen phosphorylase during the breakdown of glycogen (a substance our body uses to store glucose). The deficiency can affect the liver and muscles (subtype 3a) or only the liver (subtype 3b).

Its prevalence is estimated at approximately 1 case per 100,000 births (may be higher among North Africans).

GSD-3a is the most common subtype (85% of cases), usually develops in childhood and causes hepatomegaly or liver enlargement, growth retardation (short stature) and occasional seizures associated with low blood sugar levels. Hepatomegaly may disappear with adulthood. Muscle weakness appears slowly and progressively, affects both skeletal and cardiac muscle, and sometimes results in hypertrophic cardiomyopathy.

If the disease is not controlled in the long term, patients may develop complications such as type 2 diabetes, liver failure and hepatocellular carcinoma.

Treatment consists of a specific diet rich in protein and complex carbohydrates, with continued nasogastric tube feeding in case of hypoglycemia or frequent meals and raw starch supplementation. In addition, in patients with cardiomyopathy and myopathy, there may be potential benefits in the use of medium-chain triglycerides and/or ketogenic supplements, with or without a high-protein diet. Patients are often supplemented with vitamin D and calcium to prevent osteoporosis.