What are the symptoms? Infants with Lesch Nyhan syndrome appear normal at birth but motor delay and low-muscle tone become obvious within the first few months of life. Dystonia and choreoathetosis (involuntary jerky movement of the body) usually develop towards the end of the first year of life. Dystonia is a disorder of muscle tone producing typical contractile spasms or fixed postures, which interfere with movement and speech development. Feeding difficulties and hiatus hernia (where part of the stomach pushes its way through a hole/tear in the diaphragm) are common. Most affected individuals have moderate or severe learning difficulties (see entry Learning Disability), although some have low-average intellectual abilities. A build up of uric acid in the blood and urine results in kidney damage and the production of kidney stones. Some infants have severe kidney problems and may go develop kidney failure. Self-injurious behaviour is reported in the majority of cases. Biting of the lips, inside of the mouth and tongue or of the fingers is common. This behaviour fluctuates and may be associated with aggressive outbursts towards carers and anxiety and depression in boys. What are the causes? Affected males inherit a gene mutation on the long arm of the X chromosome (Xq26.1) that results in HPRT deficiency. Females can carry the mutation, but show no symptoms of the condition (are carriers). Sometimes the condition can occur as a result of a new mutation in a family (sporadic). How is it diagnosed? Diagnosis should be carried out in a specialist centre as it depends on a careful examination of HPRT activity in the blood. Uric acid levels will usually be raised in blood and urine, but levels may be misleading causing missed diagnosis. Nowadays, specific gene testing is carried out to confirm any suspected case. How is it treated? Allopurinol is a drug used to reduce uric acid production, but the dose must be carefully monitored as too much can produce xanthine, and will cause kidney damage and stones. It is vital to drink plenty of water as well to reduce the possibility of creating kidney stones. Normally this is given with a weak amount of potassium citrate which reduces the risk even further. Dietary advice to reduce the amounts of purine is also vital. The effectiveness of medication in treating the self-injurious behaviour has been variable, the anticonvulsant gabapentin is felt to be the medicine with greatest potential at present. Behaviour modification techniques can also be helpful in some cases. Stress reduction is viewed as a useful and effective method to help improve behaviour. In younger children, aids may be used to restrict the amount of self-injury that can occur. Management of muscle tone focuses on oral treatments with baclofen or anti-dystonic agents such as trihexyphenidyl. Treatment with botulinum toxin A injections can also be helpful. There are a few centres in the UK and internationally that are looking at using deep brain stimulation treatment in young people with Lesch Nyhan syndrome. This involves placing small wire implants into the deep part of the brain that works to control the fluidity of movement – the globus pallidus. Sadly, life expectancy is reduced, but some men are living beyond forty years of age. Inheritance patterns and prenatal diagnosis Inheritance patternsThe condition is inherited in an X-linked recessive manner. Testing to detect carriers can occur, but is not always accurate. Affected families should be referred to their regional genetics centre for investigation, advice and support. Prenatal diagnosisGenetic screening and detection of HPRT deficiency is possible in the first 12 weeks of pregnancy from a sample of cells from the developing baby. Genetic screening can also be provided within a family. Is there support? Information and support in the UK for Lesch Nyhan syndrome is provided by PUMPA (see entry Purine and Pyrimidine Metabolic diseases) and Climb (see entry Inherited Metabolic diseases).