Glycogen Storage Disease Due To Glycogen Debranching Enzyme Deficiency
Glycogen debranching enzyme (GDE) deficiency, or glycogen storage disease type 3 (GSD 3), is a form of glycogen storage disease characterized by severe muscle weakness and hepatopathy.
Epidemiology
Estimated prevalence is approximately 1/100,000 births (it may be higher among North Africans).
Clinical description
GSD 3 commonly occurs in early childhood. Children present with hepatomegaly, growth retardation and occasional seizures related to hypoglycemia. Hepatomegaly may disappear with adulthood. Muscle weakness is slowly progressive. Other frequently associated signs include muscular hypotonia and hypertrophic cardiomyopathy. Symptoms often improve at puberty, except in the few cases where cirrhosis or myopathy appears. Biological findings include hypoglycemia without acidosis, hypertriglyceridemia, and hypertransaminasemia during childhood.
Etiology
The disease is caused by mutations in the AGL gene (1p21), leading to a deficiency in the GDE that works with the glycogen phosphorylase to catabolize glycogen. The deficiency may occur in the liver and muscle (GSD 3a) or only in the liver (GSD 3b).
Diagnostic methods
The diagnosis is based on the evidence of enzymatic deficiency in fresh leukocytes, fibroblasts, or on a liver or a muscle biopsy. Unlike GSD type 1 (see this term), there is a response to glucagon after meals.
Differential diagnosis
Differential diagnoses include the other forms of glycogen storage diseases (see these terms).
Antenatal diagnosis
Prenatal diagnosis is possible by enzyme assay and/or DNA analysis.
Genetic counseling
Transmission is autosomal recessive.
Management and treatment
Treatment is based on a specific diet, with enteral nasogastric drip feeding at night in case of hypoglycemia, frequent meals, and uncooked starch supplements. For patients with myopathy, a high protein diet is also recommended.
Prognosis
Rarely, patients may develop complications such as hepatic failure or hepatocellular carcinoma.