An infant boy passes brick-red stained diapers, and workup reveals renal calculi composed of 2,8-dihydroxyadenine. Serum uric acid is normal. Enzyme assay of red cells shows absent activity of a phosphoribosyltransferase. Which enzyme is deficient and why are the stones formed?
- A Adenine phosphoribosyltransferase deficiency, allowing accumulated adenine to be oxidized by xanthine oxidase to insoluble 2,8-dihydroxyadenine ✓
- B HGPRT deficiency, causing excess hypoxanthine that precipitates as 2,8-dihydroxyadenine
- C Xanthine oxidase deficiency, causing adenine to crystallize directly in the tubules
- D UMPS deficiency, causing orotate to complex with adenine in the urine
Correct answer: A. Adenine phosphoribosyltransferase deficiency, allowing accumulated adenine to be oxidized by xanthine oxidase to insoluble 2,8-dihydroxyadenine
Explanation
APRT normally salvages free adenine to AMP using PRPP. When it is absent, adenine accumulates and is shunted to xanthine oxidase, which oxidizes it to 2,8-dihydroxyadenine, a compound far less soluble than uric acid that forms radiolucent stones. Serum uric acid remains normal, and HGPRT deficiency produces hypoxanthine and xanthine problems instead.
Reference: Williams Hematology, 10th ed.
High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP
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