Von Gierke disease (GSD type 1a) is due to glucose-6-phosphatase deficiency. Which hepatic metabolic consequences are DIRECTLY attributable to the accumulation of glucose-6-phosphate?

• A Increased glycolysis → excess acetyl-CoA → fatty liver and hypertriglyceridaemia; increased HMP shunt → excess NADPH → increased cholesterol and fatty acid synthesis; hyperuricaemia from excess PRPP ✓
• B Decreased glycolysis → impaired ATP production → hepatocyte necrosis; increased gluconeogenesis → hyperglycaemia
• C Increased glycogen synthesis only → hepatomegaly without metabolic derangements
• D Decreased HMP shunt → decreased NADPH → oxidative stress and haemolysis

Explanation

In GSD 1a, glucose-6-phosphate cannot be converted to free glucose for export. It accumulates and is shunted to glycolysis (producing excess pyruvate/acetyl-CoA → fatty acid and triglyceride synthesis → hepatic steatosis and hypertriglyceridaemia) and to the HMP shunt (producing NADPH → further lipogenesis and cholesterol synthesis). Excess fructose-6-phosphate and glyceraldehyde-3-phosphate enter glycolysis generating excess lactate (lactic acidosis). Excess glucose-6-phosphate → ribose-5-phosphate via HMP shunt → PRPP → purine synthesis → hyperuricaemia and gout. Clinical triad: hypoglycaemia, lactic acidosis, hypertriglyceridaemia, hyperuricaemia, hepatomegaly.

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

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

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