Lesch-Nyhan Syndrome

Overview :

Lesch-Nyhan syndrome was first described in 1964 by Drs. Michael Lesch and William Nyhan. The enzyme deficiency that causes the disorder was discovered in 1967 by a researcher named Seegmiller. The syndrome is caused by a severe change (mutation) in a gene that encodes an enzyme known as hypoxanthine-guanine phosphoribosyl transferase, or HPRT. This gene was identified and sequenced by Friedmann and colleagues in 1985. HPRT catalyzes a reaction that is necessary to prevent the buildup of uric acid, a nitrogenous waste product that is ordinarily excreted from the body through the kidneys. A severe mutation in the HPRT gene leads to an absence of HPRT enzyme activity which, in turn, leads to markedly elevated uric acid levels in the blood (hyperuricemia). This buildup of uric acid is toxic to the body and is related to the

symptoms associated with the disease. Absence of the HPRT enzyme activity is also thought to alter the chemistry of certain parts of the brain, such as the basal ganglia, affecting neurotransmitters (chemicals used for communication between nerve cells), acids, and other chemicals. This change in the nervous system is also related to the symptoms associated with Lesch-Nyhan syndrome.

Males with Lesch-Nyhan syndrome develop neurologic problems during infancy. Infants with Lesch-Nyhan syndrome have weak muscle tone (hypotonia) and are unable to develop normally. Affected males develop uncontrollable writhing movements (athetosis) and muscle stiffness (spasticity) over time. Lack of speech is also a common feature of Lesch-Nyhan syndrome. The most dramatic symptom of Lesch-Nyhan syndrome, however, is the compulsive self-injury seen in 85% of affected males. This self-injury involves the biting of their own lips, tongue, and finger tips, as well as head banging. This behavior leads to serious injury and scarring.

Lesch-Nyhan syndrome affects approximately one in 380,000 live births. It occurs evenly among races. Almost always, only male children are affected, although a few cases of the disorder in girls have been reported. Women carriers usually do not have any symptoms. Women carriers can occasionally develop inflammation of the joints (gout) as they get older.