A 6-month-old infant presents with hypotonia, seizures, high-pitched cry, and failure to thrive. On examination there is self-mutilation behavior, choreoathetosis, and hyperuricemia. Serum uric acid is grossly elevated. The enzyme deficiency is in the salvage pathway of purine metabolism. What enzyme is deficient in this condition?
- A Adenosine deaminase (ADA)
- B Purine nucleoside phosphorylase (PNP)
- C Xanthine oxidase
- D Hypoxanthine-guanine phosphoribosyltransferase (HGPRT) ✓
Explanation
Lesch-Nyhan syndrome is caused by complete deficiency of hypoxanthine-guanine phosphoribosyltransferase (HGPRT), an enzyme of the purine salvage pathway. Without HGPRT, hypoxanthine and guanine are not salvaged, leading to their catabolism to uric acid via xanthine oxidase. The hallmarks are severe hyperuricemia (gout, nephrolithiasis), neurological dysfunction (hypotonia evolving to dystonia and spasticity), intellectual disability, and the characteristic pathological self-mutilatory behavior (compulsive biting of fingers and lips). It is X-linked recessive. Adenosine deaminase deficiency causes SCID. Xanthine oxidase deficiency causes xanthinuria, paradoxically lowering uric acid.
Reference: Ghai Essential Pediatrics, 10th ed.
High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP
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