Learn About Lesch Nyhan Syndrome: Genetics, Clinical Features and Treatment Options

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What is Lesch Nyhan Syndrome Caused by ? - Mutations in HGPRT

  • HGPRT (hypoxanthine-guanine phosphoribosyl transferase) is encoded by a single structural gene and is essential for the metabolism of purines, a component of DNA.
  • More than 300 mutations have been identified in the HGPRT gene which give rise to lesch nyhan syndrome.
  • The disease is of X-linked recessive inheritance, thus boys are affected whereas girls are usually asymptomatic carriers.
  • Lesch Nyhan is rare, with an estimated occurrence of 1 in 380,000 live births in Canada and 1 in 235,000 in Spain.
  • Although the mutation can be passed from parent to child, many cases appear to be due to spontaneous (new) mutations.


  • Biochemical findings: high levels of uric acid in the blood and urine. Orange uric acid crystals may be noticed in diapers during the first weeks of life.
  • Enzymatic tests: determination of HGPRT activity in red blood cells or fibroblasts.
  • Clinical findings: children are often healthy at birth with diagnosis being made when psychomotor delay (e.g. failure to crawl) and dytonia (uncontrolled muscular movements) are noticed.
  • Molecular tests can confirm diagnosis of sufferers and allow the identification of carriers within families. Prenatal diagnosis can be performed from chorionic villous or amniotic cells. DNA analysis together with genetic counselling can help families make choices about future pregnancies.

Renal and Neurological Symptoms

  • Patients partially deficient in HGPRT show less severe symptoms, at its mildest the condition may be limited to gout.
  • HGPRT deficiency is associated with kidney disease and gout. Some patients show neonatal acute renal failure.
  • Neurological manifestations: e.g.cognitive deficit and self-destructive behaviour e.g. biting of fingers and lips. How the HGPRT deficiency causes this neuropathology is not totally clear.
  • The majority of patients have below average intelligence compared to the general population, but many achieve age appropriate reading levels.
  • Around half of lesch nyhan patients suffer occasional seizures.


The incomplete understanding of the pathology of lesch nyhan has hampered the development of adequate therapies. There is presently no cure, but some treatment options exist.

  • Uric acid overproduction can be treated with the drug allopurinol, but the dose must be carefully controlled
  • Dystonia (involuntary muscle spasms) can be managed with drugs such as diazepam and barbiturates.
  • Physiotherapy can be beneficial.
  • Self-injury can be managed by a combination of protective barriers e.g. lip guards and behavioural treatments e.g. minimising exposure to stressful stimuli.
  • Bone marrow transplantation may increase HGPRT levels in red blood cells, but this has little effect on neurological symptoms.
  • Gene Therapy: is being actively pursued for this condition and may offer hope for the future.

Further Information and Support

CLIMB (children living with inherited metabolic diseases) is a UK based organisation which aims to provide information and support as well as raise funding for medical research into inherited metabolic conditions.

Lesch-Nyhan International Study group. Provide a resource of information on everything from latest medical research to specialist care providers. www.lesch-nyhan.org


Nephrolithiasis Related to Inborn Metabolic Diseases. P.Cochat, V.Pichault, J.Bacchetta, L.Dubourg, J.Sabot, C.Saban, M.Daudon & A.Liutkus. Pediatric Nephrology, 2010, Vol 25, P415–424.

CLIMB website: www.climb.org.uk