Lesch-Nyhan syndrome

X‑linked recessive HGPRT enzyme deficiency that blocks purine salvage, causing hyperuricemia (↑uric acid) with early-onset gout, neurologic disability, and compulsive self‑mutilation.

• Classic inborn error linking metabolism and neurology – a high-yield example of how a single enzyme defect (HGPRT) leads to gout in a child with severe neurobehavioral issues (self-harm). Often tested on exams as a biochemistry-genetics tie-in.

• Almost exclusively in infant boys (X-linked): hypotonia and developmental delay in infancy; by toddler age, they exhibit self-biting (fingers, lips) and other self-injury (e.g., head banging).
• Neurologic: dystonia, choreoathetosis, spasticity, and intellectual disability. They usually cannot walk (wheelchair-bound); speech is often impaired.
• Uric acid overproduction: causes orange "sand" (sodium urate crystals) in diapers during infancy, early kidney stones or hematuria, and pediatric gouty arthritis or tophi.

1. Suspect LNS in a male child with the triad of hyperuricemia, neurologic dysfunction, and self-injurious behavior. Check serum/urine uric acid levels (typically very high).
2. Confirm diagnosis via HPRT1 gene mutation testing or an HGPRT enzyme assay (near-absence of HGPRT activity <2% is diagnostic).
3. Differentiate from partial HGPRT deficiency (Kelley-Seegmiller syndrome) which causes hyperuricemia and early gout but no neurologic symptoms or self-mutilation.
4. Screen for complications: renal ultrasound for uric acid stones if flank pain or hematuria; evaluate joints for gouty tophi or arthritis.

1. No cure – supportive care only. For hyperuricemia: allopurinol (or febuxostat) to reduce uric acid and prevent gout/stone complications; also low-purine diet and hydration.
2. Self-mutilation: use protective gear (padded restraints, mouth guards) and behavioral interventions; severe cases may need tooth extraction. Medications (e.g., benzodiazepines, baclofen) can be tried for neurologic symptoms.
3. Manage spasticity/dystonia with therapy and meds for comfort. Provide multidisciplinary support (neurology, rehab, nutrition) to improve quality of life.

• Mnemonic: HGPRT features → Hyperuricemia, Gout, P (aggressive self-harm), R (intellectual disability), T (dysTonia).
• Remember orange crystals in diaper = urate (think Lesch-Nyhan in a baby boy).
• A young child with gout or kidney stones ("juvenile gout") is a big clue – consider HGPRT deficiency.

• Severe self-injury (deep bites) causing bleeding or infection risk – may require urgent intervention (sedation or tooth removal).
• Any hematuria or renal colic in LNS → suspect uric acid stones (need prompt management to avoid kidney damage).

1. Male infant with neurodevelopmental delays + self-harm → suspect Lesch-Nyhan (especially if orange crystals in diapers).
2. Check uric acid; if elevated, confirm with HPRT1 genetic test or enzyme assay.
3. Start allopurinol to control uric acid; counsel family on X-linked inheritance.
4. Ensure safety: protective measures or dental extractions to prevent self-mutilation.
5. Monitor long-term for kidney stones and gout complications; provide supportive neuro care.

• Toddler boy with developmental delay who bites his fingers and lips, has spastic movements, and signs of gout (swollen toe or kidney stone) → Lesch-Nyhan syndrome.
• Biochemistry question: absent HGPRT → can't salvage hypoxanthine/guanine → excess uric acid + ↑de novo purine synthesis (↑PRPP amidotransferase). Often answer to "boy with self-mutilation + gout".