A child who was normal at bih develops chronic liver failure and muscle weakness at 3 months of age. On investigations, serum glucose is low, along with ketoacidosis and decreased pH. ALT and AST are raised. Blood lactate and uric acid levels are normal. Intravenous glucagon given after meals raises the blood glucose levels, but does not raise glucose when given after an overnight fast. Liver biopsy shows increased glycogen in liver. Which is the enzyme likely to be defective in this child?
(A) Glucose-6-phosphatase (B) Muscle phosphorylase (C) Branching enzyme (D) Debranching enzyme
(D) Ans: D: Debranching enzyme(Ref: Nelson 20/e p717-720; Harrison 19/e p433 e-2, 18Ie p3200, 3201)In this child, a combination of liver and muscle involvement with ketoacidosis and raised liver enzymes points towards Type III glycogen storage disease, i.e. Cori's disease caused by deficiency of debranching enzyme.Type IIIa Glycogen Storage Disease or Cori's Disease or Forbes Disease:Due to deficiency ofglycogen debranching enzyme activity.Debranching enzyme, together with phosphorylase, is responsible for complete degradation of glycogen. When debranching enzyme is defective, glycogen breakdown is incomplete and an abnormal glycogen with sho outer branch chains and resembling limit dextrin accumulates.Deficiency of glycogen debranching enzyme causes hepatomegaly, hypoglycemia, sho stature, variable skeletal myopathy & variable eardiomyopathy.