A 2-year-old boy presents with self-mutilation (biting his fingers and lips to the point of tissue destruction), intellectual disability, choreoathetosis, and hyperuricemia. Serum uric acid is 11.4 mg/dL. What is the molecular defect responsible for this condition?

• A Deficiency of adenine phosphoribosyltransferase (APRT) — X-linked
• B Excess activity of phosphoribosyl pyrophosphate (PRPP) synthetase — autosomal dominant
• C Deficiency of hypoxanthine-guanine phosphoribosyltransferase (HGPRT) — X-linked recessive ✓
• D Deficiency of purine nucleoside phosphorylase (PNP) — autosomal recessive

Explanation

Lesch-Nyhan syndrome is caused by near-complete deficiency of HGPRT (encoded by HPRT1 gene on X chromosome, Xq26.2), an enzyme in the purine salvage pathway. HGPRT deficiency leads to failure of recycling hypoxanthine and guanine, causing massive uric acid overproduction via the de novo synthesis pathway. The neurological phenotype (choreoathetosis, spasticity, cognitive impairment, and the pathognomonic compulsive self-mutilation) is attributed to dopaminergic neurotransmitter dysfunction. APRT deficiency causes 2,8-dihydroxyadenine nephrolithiasis but no neurological disease. PNP deficiency causes combined immunodeficiency.

Reference: Ghai Essential Pediatrics, 10th ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.