A neonate presents on day 3 with lethargy, poor feeding, and profound hypoglycemia. Liver biopsy reveals massive hepatomegaly with glycogen accumulation. Enzyme assay shows absent glucose-6-phosphatase activity. Which of the following best explains why glucagon administration fails to correct hypoglycemia in this infant?
- A Glucagon receptor is downregulated in hepatocytes
- B Glucose-6-phosphate cannot be dephosphorylated to release free glucose ✓
- C Phosphorylase kinase is absent, preventing glycogenolysis
- D GLUT2 transporter is absent from the hepatocyte membrane
Correct answer: B. Glucose-6-phosphate cannot be dephosphorylated to release free glucose
Explanation
In Glycogen Storage Disease type Ia (von Gierke disease), glucose-6-phosphatase is absent. Although glucagon activates glycogenolysis normally (via cAMP-PKA-phosphorylase pathway), the resulting glucose-6-phosphate cannot be converted to free glucose for export because the terminal step is blocked. Free glucose cannot be released into the blood, so hypoglycemia persists regardless of glucagon. GLUT2 and phosphorylase kinase are intact in GSD Ia.
Reference: Harper's Illustrated Biochemistry, 32nd ed.
High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP
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