Biochemistry · Carbohydrate Metabolism (Glycolysis, Gluconeogenesis, Glycogen, HMP Shunt)

A newborn presents with lactic acidosis, hypoglycemia, hepatomegaly, and elevated blood lactate after feeding. Erythrocyte transketolase and glucose tolerance test are normal. Liver biopsy shows glycogen accumulation. The enzyme defect is MOST likely in:

  • A Glucose-6-phosphatase (Von Gierke disease, GSD type Ia)
  • B Glycogen debranching enzyme (Cori's disease, GSD type III)
  • C Liver phosphorylase (Hers disease, GSD type VI)
  • D Glycogen branching enzyme (Andersen disease, GSD type IV)
Correct answer: A. Glucose-6-phosphatase (Von Gierke disease, GSD type Ia)

Explanation

Von Gierke disease (GSD type Ia) presents in infancy with severe fasting hypoglycemia, lactic acidosis (lactate is used for gluconeogenesis that is also blocked), hyperuricemia, and hyperlipidemia, with marked hepatomegaly from glycogen and fat accumulation. The absence of glucose-6-phosphatase prevents release of free glucose from both glycogenolysis and gluconeogenesis (both produce G6P which cannot be hydrolyzed). Lactate accumulates because gluconeogenesis is blocked. GSD III causes milder hypoglycemia with elevated transaminases. GSD VI causes mild hypoglycemia without lactic acidosis. GSD IV causes progressive cirrhosis with abnormal glycogen.

Reference: Harper's Illustrated Biochemistry, 32nd ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

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