Lesch-Nyhan syndrome (LNS) is a rare, inherited disorder caused by a deficiency of the enzyme hypoxanthine-guanine phosphoribosyltransferase (HPRT).

LNS is an X-linked recessive disease — the gene is carried by the mother and passed on to her son. However, one-third of all cases arise de novo (from new mutations) and do not have a family history. LNS is present at birth in baby boys. There are a few rare cases in the world of affected females. It affects about one in 380,000 live births.

The lack of HPRT causes a build-up of uric acid in all body fluids, and leads to the following symptoms which appear in the first year of life:

• Severe gout
• Poor muscle control
• Moderate retardation

A striking feature of LNS is self-mutilating behaviors – characterized by lip and finger biting – that begin in the second year of life. Abnormally high uric acid levels can cause sodium urate crystals to form in the joints, kidneys, central nervous system, and other tissues of the body, leading to gout-like swelling in the joints and severe kidney problems. Neurological symptoms include:

• Facial grimacing
• Involuntary writhing
• Repetitive movements of the arms and legs similar to those seen in Huntington’s disease

Because a lack of HPRT causes the body to poorly utilize vitamin B12, some boys may develop a rare disorder called megaloblastic anemia. Most, but not all, persons with this deficiency have severe mental and physical problems throughout life.

The prognosis for individuals with LNS is poor. Death is usually due to renal failure in the first or second decade of life.

Treatment for LNS is symptomatic. Gout can be treated with allopurinol to control excessive amounts of uric acid. Kidney stones may be treated with lithotripsy, a technique for breaking up kidney stones using shock waves or laser beams. There is no standard treatment for the neurological symptoms of LNS. Some may be relieved with the drugs carbidopa/levodopa, diazepam, phenobarbital, or haloperidol.