A 3-year-old boy demonstrates self-mutilation, choreoathetosis, intellectual disability, and hyperuricaemia. Enzyme assay shows absent HGPRT activity. Which statement about the biochemical consequences is MOST accurate?

• A HGPRT deficiency blocks de novo purine synthesis, causing accumulation of IMP
• B HGPRT deficiency causes adenosine deaminase deficiency and lymphopenia
• C Absent HGPRT leads to orotic aciduria due to pyrimidine pathway diversion
• D Failure of the purine salvage pathway floods de novo synthesis, overproducing uric acid via xanthine ✓

Explanation

Hypoxanthine-guanine phosphoribosyltransferase (HGPRT) normally recycles hypoxanthine and guanine back to IMP and GMP via PRPP. In Lesch-Nyhan syndrome (X-linked HGPRT deficiency), this salvage is lost, causing PRPP accumulation and unregulated upregulation of de novo purine synthesis. The excess purines are ultimately oxidised to uric acid via xanthine oxidase, causing severe hyperuricaemia. ADA deficiency is a separate cause of SCID and does not relate to HGPRT.

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

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

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