GSD Type 3

Also known as Debrancher enzyme deficiency; Cori disease; Forbes disease

Defect: Deficiency of glycogen debrancher enzyme causing abnormal accumulation of glycogen in affected tissues.

  • Type IIIa – generalized defect involving both liver and muscle. Accounts for 85% of patients
  • Type IIIb – defect is limited to liver only.

Cause: Mutation in the debrancher gene, which is localized to chromosome 1p21.

Incidence: Approximately 1 in 100,000 live births.

Signs & symptoms – depend on tissue involvement

  • Patients with liver involvement may be indistinguishable in infancy from GSD I, and typically have enlarged liver and ketotic hypoglycemia however hypoglycemia improves with age.
  • Variable myopathy can occur, which is minimal in childhood, but can become prominent in adulthood.
  • Associated laboratory studies include profound elevation of serum transaminases (often worse than GSD I),
  • Elevated creatine kinase and hyperlipidemia.
  • Long term complications include short stature, idiopathic hypertrophic cardiomyopathy (enlarged weakened heart muscle) and hepatic adenomas (liver tumors).

Diagnosis

  • Fasting studies resulting in ketotic hypoglycemia (high ketones, high glucose) without the hyperlacticacidemia (high lactic acid).
  • No blood sugar response to glucagon during fasting but blood sugar rises after a carbohydrate-rich meal.
  • Liver and muscle biopsy

Treatment Standard Therapy – Continuous glucose delivery like GSD I. After infancy, uncooked cornstarch given every 6 hours will maintain normal blood sugar level, improve growth and improve laboratory abnormalities. Patients do not need to restrict fructose or galactose. A high protein may be beneficial.