Lesch–Nyhan syndrome is a rare inherited disorder in which there are high levels of uric acid. It presents with a wide range of neurological, renal, musculoskeletal and behavioural issues, the most common of which is self-mutilation (in 85% of affected children).

Lesch–Nyhan syndrome was first described by Doctors Michael Lesch and William Nyhan in 1964. This syndrome is also known by some other names including Lesch–Nyhan disease, Nyhan syndrome, juvenile gout, hypoxanthine-guanine phosphoribosyl transferase (HGPRT or HPRT) deficiency, X-linked hyperuricaemia, and choreoathetosis self-mutilation syndrome.

Lesch–Nyhan syndrome is rare, occurring in 1 out of every 100,000 to 380,000 live births. It presents almost exclusively in males whose mothers were carriers for mutations in the HPRT-1 gene (the Lesch–Nyhan gene), with female presentations being very rare. A mother with this gene has a 25% chance of producing a son who suffers from this disorder, a 25% chance of an unaffected son, a 25% of an unaffected daughter and a 25% chance of a carrier daughter.

Lesch–Nyhan syndrome is an X chromosome-linked recessive genetic disorder due to a lack or near-lack of the HGPRT enzyme. This enzyme is needed to break down purines, which are found in foods like meats and legumes. Purines are colourless crystalline compounds with basic properties that form uric acid on oxidation; they include the bases adenine and guanine, constituents of nucleic acids, as well as many alkaloids such as caffeine and theophylline. The accumulation of purines leads to a build-up of uric acid and affects multiple organs.

Lesch–Nyhan syndrome is characterised by:

The biting of fingers and lips, scratching of the face and gouging of the eyes resulting in:

Gouty tophi (nodular masses of monosodium urate crystals that develop and appear as firm lumps under the skin) form on the ears and over the joints of the fingers and toes.

The diagnosis of Lesch–Nyhan syndrome is based on careful patient history, physical examination findings, and blood tests to detect high levels of uric acid. Where available, genetic testing confirms the presence of an abnormal HPRT-1 gene.

The differential diagnosis for Lesch–Nyhan syndrome includes:

The treatment for Lesch–Nyhan syndrome depends on the individual patient’s symptoms, but may include:

No methods, to date, have been consistently found to reduce self-mutilating behaviour. Psychotherapy, restraints, a mouth/dental guard, and dental extraction have been used.

Death from Lesch–Nyhan syndrome usually occurs in the second or third decade of life due to infection or renal failure.