In glycogen storage disease type I (Von Gierke disease), which enzyme is deficient and directly explains fasting hypoglycemia and lactic acidosis?

Introduction / Context:Glycogen storage diseases (GSDs) are enzyme deficiencies affecting glycogen metabolism. Von Gierke disease (GSD I) is a prototypical disorder with severe fasting hypoglycemia due to failure to release free glucose from the liver and kidney.

Given Data / Assumptions:

• Patients present with hepatomegaly, fasting hypoglycemia, lactic acidosis, hyperuricemia, and hyperlipidemia.
• Defect lies in the terminal step of gluconeogenesis and glycogenolysis.

Concept / Approach:Glucose-6-phosphatase hydrolyzes glucose-6-phosphate to free glucose and inorganic phosphate in the endoplasmic reticulum of hepatocytes and renal cortex. Its deficiency traps glucose-6-phosphate, preventing glucose export, driving glycolysis and lactate production, and altering lipid and uric acid metabolism.

Step-by-Step Solution:

Verification / Alternative check:Biochemical testing shows elevated liver glycogen with normal structure; genetic testing finds G6PC or G6PT complex variants; metabolic profile matches GSD I.

Why Other Options Are Wrong:

• Glycogen phosphorylase deficiency (Hers disease) presents differently.
• PFK-1 deficiency affects glycolysis (Tarui disease), not classical GSD I features.
• Debranching enzyme deficiency is GSD III (Cori/Forbes disease).
• Fructose-1,6-bisphosphatase deficiency causes gluconeogenic failure but is a distinct disorder.

Common Pitfalls:Confusing GSD I with GSD III; overlooking the ER transport component (G6PT) that can phenocopy G6Pase deficiency.

Final Answer:Glucose-6-phosphatase