A 4-year-old boy with hepatomegaly, fasting hypoglycemia, lactic acidosis, and doll-like facies develops recurrent attacks of gouty arthritis beginning in early childhood. Which mechanism best explains his hyperuricemia?
- A Defective renal tubular secretion of urate caused by chronic tubular injury
- B Reduced activity of urate oxidase inherited along with the same chromosomal deletion
- C Excess glucose-6-phosphate shunted through the pentose phosphate pathway, raising ribose-5-phosphate and PRPP, which accelerates de novo purine synthesis ✓
- D Increased salvage of free purine bases because of compensatory overexpression of HGPRT
Correct answer: C. Excess glucose-6-phosphate shunted through the pentose phosphate pathway, raising ribose-5-phosphate and PRPP, which accelerates de novo purine synthesis
Explanation
This child has type I glycogen storage disease (von Gierke disease, glucose-6-phosphatase deficiency). Trapped glucose-6-phosphate is diverted into the pentose phosphate pathway, increasing ribose-5-phosphate and hence PRPP. Elevated PRPP drives glutamine-PRPP amidotransferase, accelerating de novo purine synthesis and uric acid production. Renal urate handling may contribute later, but the primary mechanism is substrate-driven purine overproduction, not secretion defects or altered urate oxidase.
Reference: Robbins and Cotran Pathologic Basis of Disease, 10th ed.
High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP
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