A 3-year-old boy exhibits self-mutilating behavior, choreoathetosis, intellectual disability, and elevated serum uric acid. His red blood cells show nearly absent HGPRT activity. Which salvage pathway substrate accumulates to drive hyperuricemia?

• A Adenosine
• B Xanthine alone
• C Orotic acid
• D Hypoxanthine and guanine, channeled to xanthine oxidase ✓

Explanation

HGPRT (hypoxanthine-guanine phosphoribosyltransferase) normally salvages hypoxanthine and guanine back to IMP and GMP using PRPP. In Lesch-Nyhan syndrome (X-linked HGPRT deficiency), hypoxanthine and guanine cannot be salvaged and are instead degraded by xanthine oxidase: hypoxanthine → xanthine → uric acid. Excess PRPP also drives de novo purine synthesis. Orotic acid accumulation occurs in pyrimidine synthesis defects (UMP synthase deficiency).

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

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

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