A 3-month-old infant presents with hypoglycemia, hepatomegaly, and lactic acidosis that worsens after glucose administration. Liver biopsy shows glycogen accumulation. Enzyme assay reveals deficiency of glucose-6-phosphatase. Which gluconeogenic substrate would be LEAST helpful in managing hypoglycemia in this patient?
- A Fructose ✓
- B Galactose
- C Alanine
- D Glycerol
Explanation
In glucose-6-phosphatase deficiency (Type Ia GSD — von Gierke disease), all gluconeogenic substrates funnel into glucose-6-phosphate, which cannot be dephosphorylated to free glucose. Fructose is converted via fructose-1-phosphate to DHAP and glyceraldehyde-3-phosphate, eventually yielding glucose-6-phosphate that accumulates further, worsening lactic acidosis. Alanine, glycerol, and galactose similarly converge on glucose-6-phosphate. Fructose is particularly harmful because its initial metabolism bypasses the rate-limiting phosphofructokinase step, flooding the pathway rapidly. Cornstarch feeding (uncooked) that slowly releases glucose is the mainstay therapy to maintain normoglycemia.
Reference: Harper's Illustrated Biochemistry, 32nd ed.
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Written and medically reviewed by the StethoPrep medical team.