Lesch-Nyhan syndrome was first described in 1964 by Dr. Michael Lesch and Dr. William Nyhan. Males with Lesch-Nyhan syndrome develop neurological 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 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. Women carriers usually do not have any symptoms. Women carriers can occasionally develop inflammation of the joints (gout) as they get older.
Causes and symptoms
The syndrome is caused by a severe change (mutation) in the HPRT gene. Since the HPRT gene is located on the X chromosome, Lesch-Nyhan syndrome is considered an X-linked disorder and therefore only affects males.
The HPRT gene is responsible for the production of the enzyme called hypoxanthine-guanine phosphoribosyltransferase (HPRT). HPRT catalyzes a reaction that is necessary to prevent the buildup of uric acid. 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.
At birth, males with Lesch-Nyhan syndrome appear completely normal. Development is usually normal for the first few months. Symptoms develop between three to six months of age. Sand-like crystals of uric acid in the diapers may be one of the first symptoms of the disease. The baby may be unusually irritable. Typically, the first sign of nervous system impairment is the inability to lift their
head or sit up at an appropriate age. Many patients with Lesch-Nyhan will never learn to walk. By the end of the first year, writhing motions (athetosis), and spasmodic movements of the limbs and facial muscles (chorea) are clear evidence of defective motor development.
The compulsive self-injury associated with Lesch-Nyhan syndrome begins, on average, at three years. The self-injury begins with biting of the lips and tongue. As the disease progresses, affected individuals frequently develop finger biting and head banging. The self-injury can increase during times of stress.
Males with Lesch-Nyhan disease may also develop kidney damage due to kidney stones. Swollen and tender joints (gout) is another common problem.
Holly Ann Ishmael MS, CGC, Rosalyn Carson-DeWitt MD, The Gale Group Inc., Gale, Detroit,