A 4-month-old infant is brought to the clinic with severe hypoglycemia, lactic acidosis, hyperuricemia, and hepatomegaly with doll-like facies. Fasting blood glucose fails to rise after administration of glucagon. Which enzyme is deficient?

Answer and explanation

Correct answer: C. Glucose-6-phosphatase (Von Gierke disease / Type I GSD)

  1. Step 1: Analyze the clinical constellation: profound fasting hypoglycemia, severe lactic acidosis (due to shunting of glycolytic intermediates into lactate), hyperuricemia, and massive hepatomegaly are classic for Glycogen Storage Disease Type I (Von Gierke disease).
  2. Step 2: The defect lies in glucose-6-phosphatase (or the G6P translocase in Type Ib), the final shared step of both gluconeogenesis and glycogenolysis. Because glucose-6-phosphate cannot be dephosphorylated to free glucose in hepatocytes, glucagon administration cannot elevate blood glucose.
Answer
Glucose-6-phosphatase (Von Gierke disease / Type I GSD).
Why not the others: Lysosomal -1,4-glucosidase (Pompe disease / Type II GSD) presents primarily with cardiomegaly, hypotonia, and early death without severe hypoglycemia; Debranching enzyme (Cori disease / Type III GSD) features milder hypoglycemia, normal blood lactate levels, and accumulation of limit dextrin-like structures; Muscle glycogen phosphorylase (McArdle disease / Type V GSD) presents in adolescents or adults with exercise-induced muscle cramps and myoglobinuria.

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