Lesch-Nyhan syndrome

Lesch-Nyhan syndrome is a condition characterized by the overproduction and accumulation of uric acid, a waste product of normal chemical processes that is found in blood and urine. The overproduction of uric acid can cause gouty arthritis (arthritis caused by an accumulation of uric acid in the joints), kidney stones, and bladder stones. Problems with the nervous system and behavioral disturbances are also characteristic of this disorder. Abnormal involuntary muscle movements such as flexing, jerking, and flailing are often displayed by people affected with this disorder. People with Lesch-Nyhan syndrome usually cannot walk, require assistance sitting, and are generally wheelchair-bound. Self-injury, including biting and head banging, is the most common and distinctive behavioral problem in those with Lesch-Nyhan syndrome.

The prevalence of Lesch-Nyhan syndrome is approximately 1 in 380,000 individuals. This condition occurs with a similar frequency in all populations.

Mutations in the HPRT1 gene cause Lesch-Nyhan syndrome.

Mutations in the HPRT1 gene cause a severe deficiency of the enzyme hypoxanthine phosphoribosyltransferase 1. This enzyme is responsible for recycling purines, a type of building block of DNA and its chemical cousin RNA. When this enzyme is lacking, the breakdown of purines results in abnormally high levels of uric acid in the body. It is unclear how a shortage of this enzyme causes the neurological and behavioral problems characteristic of Lesch-Nyhan syndrome.

Read more about the HPRT1 gene.

This condition is inherited in an X-linked recessive pattern. The gene associated with this condition is located on the X chromosome, which is one of the two sex chromosomes. In males (who have only one X chromosome), one altered copy of the gene in each cell is sufficient to cause the condition. In females (who have two X chromosomes), a mutation would have to occur in both copies of the gene to cause the disorder. Because it is unlikely that females will have two altered copies of this gene, males are affected by X-linked recessive disorders much more frequently than females. A striking characteristic of X-linked inheritance is that fathers cannot pass X-linked traits to their sons.