[Durgical](https://durgical.com/en/) › [DurgiPedia](https://durgical.com/en/durgipedia/) › [Conditions](https://durgical.com/en/conditions/) › Lesch-Nyhan syndrome [Conditions](https://durgical.com/en/conditions/) · [Metabolism: purines and pyrimidines](https://durgical.com/en/conditions/) # Lesch-Nyhan syndrome An inherited disorder of boys caused by missing HGPRT: excess uric acid, movement problems and self-injuring behaviour. Updated 2026-11-01 ## Structures involved Tap one to see what it is and open it in 3D. - [Caudate nucleus](https://durgical.com/en/anatomy/caudate-nucleus/) - [Putamen](https://durgical.com/en/anatomy/putamen/) - [Kidneys](https://durgical.com/en/anatomy/kidney/) - [Globus pallidus](https://durgical.com/en/anatomy/globus-pallidus/) - [Substantia nigra](https://durgical.com/en/anatomy/substantia-nigra/) - [Ureters](https://durgical.com/en/anatomy/ureter/) - [Urinary bladder](https://durgical.com/en/anatomy/urinary-bladder/) ## In biochemistry - [Glutamine-PRPP amidotransferase](https://durgical.com/en/biochemistry/enzymes/glutamine-prpp-amidotransferase/) - [Hypoxanthine-guanine phosphoribosyltransferase (HGPRT)](https://durgical.com/en/biochemistry/enzymes/hypoxanthine-guanine-phosphoribosyltransferase/) - [PRPP (phosphoribosyl pyrophosphate)](https://durgical.com/en/biochemistry/molecules/prpp/) - [IMP (inosine monophosphate)](https://durgical.com/en/biochemistry/molecules/imp/) - [Uric acid](https://durgical.com/en/biochemistry/molecules/uric-acid/) - [Hypoxanthine](https://durgical.com/en/biochemistry/molecules/hypoxanthine/) ## What it is Complete deficiency of hypoxanthine-guanine phosphoribosyltransferase (HPRT1 gene, X-linked) that causes uric acid overproduction and a severe basal ganglia disorder. ## Who gets it Very rare: about 1 in 235,000 to 380,000 people, almost always males. There are no specific registries in Colombia; it is diagnosed in genetics and paediatric neurology centres. ## Causes - Pathogenic variants of the HPRT1 gene on the X chromosome - X-linked recessive inheritance: carrier mothers; about a third of cases are new mutations ## Risk factors - Male sex - Carrier mother or family history of affected males ## Pathophysiology Without HGPRT, hypoxanthine and guanine are not recycled and are degraded to uric acid; spare PRPP also speeds de novo purine synthesis. Urate production rises several-fold, with crystals in kidneys and joints. In the brain, loss of the enzyme disturbs the development of dopaminergic neurons of the basal ganglia; hence the dystonia and self-injury, which uric acid does not explain and which do not improve when it is lowered. ## Classification - Classic Lesch-Nyhan (almost no activity) - Intermediate variants with neurological disease without self-injury - Partial deficiency: HPRT-related hyperuricaemia (Kelley-Seegmiller), with gout and stones ## Symptoms and signs - Orange crystals («sand») in the nappy from the first months - Motor delay and hypotonia around 3–6 months, then dystonia and involuntary movements - Compulsive self-injury: biting lips, [tongue](https://durgical.com/en/anatomy/tongue/) and fingers, from age 2–3 - Mild to moderate intellectual disability and aggressive behaviour - Gout and kidney stones in adolescence or earlier - Difficulty swallowing and speaking ## Red flags - Haematuria, flank pain or reduced urine output (stones or obstruction) - Serious self-inflicted injuries or wound infection - Choking and coughing when eating (aspiration risk) ## Diagnosis **Clinical** A boy with motor delay, dystonia and self-injury, with urate crystals in the nappy or early gout. **Tests** High blood uric acid and urine uric acid/creatinine ratio; HGPRT activity in red cells or fibroblasts; HPRT1 genetic testing (also for carriers and prenatal diagnosis). **Imaging** Renal ultrasound to look for stones and nephrocalcinosis; brain MRI is usually normal or shows mild basal ganglia atrophy. ## Treatment **Medical** Allopurinol to lower uric acid and protect the [kidneys](https://durgical.com/en/anatomy/kidney/); it does not correct the neurological symptoms **Lifestyle** Plenty of fluids to keep urine dilute **Conservative** Protection against self-injury: splints, gloves, mouth guards and sometimes tooth extraction **Medical** Drugs for dystonia, spasticity and behaviour, case by case **Rehabilitation** Physical, occupational and speech therapy; behavioural support with positive reinforcement **Procedure** Deep brain stimulation in specialised centres for severe cases ## Complications - Chronic kidney disease from urate nephropathy - Xanthine stones during allopurinol treatment - Aspiration pneumonia - Mutilation from self-injury ## Prognosis Most patients survive into their second or third decade; the most frequent causes of death are aspiration pneumonia, kidney failure and sudden death. ## Prevention - Genetic counselling and carrier testing in affected families ## Test yourself Think of the answer, then tap the question to see it. ## Which enzyme is missing in Lesch-Nyhan syndrome, and how is it inherited? HGPRT (HPRT1 gene); X-linked recessive inheritance, which is why it affects boys. ## Why does allopurinol not improve self-injury in Lesch-Nyhan syndrome? The neurological symptoms come from dopaminergic dysfunction of the basal ganglia, not from uric acid. ## Which early sign may the family notice in the nappy? Orange urate crystals («sand»). [Add to my cards (3)](https://durgical.app/estudiar/?add=/en/conditions/lesch-nyhan-syndrome/) ## Related conditions - [Hereditary xanthinuria](https://durgical.com/en/conditions/hereditary-xanthinuria/) - [Gout](https://durgical.com/en/conditions/gout/) - [Kidney stones (urolithiasis)](https://durgical.com/en/conditions/kidney-stones/) - [Chronic kidney disease](https://durgical.com/en/conditions/chronic-kidney-disease/) Educational information, not medical advice. For any symptom, see a health professional. Sources: [Lesch-Nyhan syndrome: MedlinePlus Genetics](https://medlineplus.gov/genetics/condition/lesch-nyhan-syndrome/) (MedlinePlus, US National Library of Medicine, 2026); [HPRT1 gene: MedlinePlus Genetics](https://medlineplus.gov/genetics/gene/hprt1/) (MedlinePlus, US National Library of Medicine, 2026); Textbook of Biochemistry for Medical Students, 6th ed. (Jaypee Brothers Medical Publishers (Vasudevan DM, Sreekumari S, Vaidyanathan K), 2011). [← All conditions](https://durgical.com/en/conditions/) ## **Spotted a mistake?** We are always improving for the community. Tell us what is wrong and our team will review it. Report a mistake Representative model, for educational purposes only. --- Source: https://durgical.com/en/conditions/lesch-nyhan-syndrome/ License: CC BY 4.0 (https://creativecommons.org/licenses/by/4.0/). Cite as: DurgiPedia (durgical.com), https://durgical.com/en/conditions/lesch-nyhan-syndrome/