A 2-year-old boy is evaluated for severe intellectual disability, self-injurious behavior (lip and finger biting causing mutilation), hyperuricemia, and gout-like arthropathy. Enzymatic assay reveals near-absent hypoxanthine-guanine phosphoribosyltransferase (HGPRT) activity. What is the inheritance pattern and primary metabolic consequence?
- A Autosomal recessive; accumulation of adenosine
- B X-linked recessive; overproduction of uric acid from de novo purine synthesis ✓
- C X-linked dominant; deficiency of adenosine deaminase
- D Autosomal dominant; deficiency of xanthine oxidase
Explanation
Lesch-Nyhan syndrome is X-linked recessive, caused by mutations in HPRT1 encoding HGPRT on chromosome Xq26. HGPRT normally recycles hypoxanthine and guanine via the salvage pathway; its absence causes these purines to be degraded via xanthine oxidase to uric acid, and simultaneously increases de novo purine synthesis (loss of negative feedback). This results in massive urate overproduction causing gout, renal stones, and renal failure. The neurological features (intellectual disability, dystonia, self-mutilation) are due to dopaminergic neuronal dysfunction, particularly in the basal ganglia. Allopurinol reduces uric acid but does not prevent neurological manifestations.
Reference: Ghai Essential Pediatrics, 10th ed.
High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP
Written and medically reviewed by the StethoPrep medical team.