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Lesch-Nyhan Syndrome
Sunday, 31 August 2003
Monday, 12 January 2004
Hypoxanthine-Guanine Phosphoribosyl Transferase Deficiency


Lesch-Nyhan syndrome (LNS) is a hereditary condition in which there is overproduction of a substance called uric acid in the body, as well as neurologic and behavior problems. Enzymes are involved in getting rid of uric acid in the blood. One of these enzymes is called "hypoxanthine-guanine phosphoribosyl transferase (HPRT)". When there is a deficiency of HPRT, uric acid accumulates and causes the symptoms of LNS.


This rare condition affects about 1 in 380,000 individuals. LNS almost always occurs in males. This condition occurs in most ethnicities and races around the world.

Signs and Symptoms

Symptoms usually begin between the ages of 3-6 months in these boys. The infant’s diapers may have orange-colored crystal-like deposits (“orange sand”), and the urine may be pink or reddish in color (hematuria). He may go on to develop kidney stones (nephrolithiasis) or kidney failure. As he develops, he may be slow to learn how to roll over, sit, or crawl and may never learn to walk. This motor delay is due to muscle weakness (hypotonia). Weak muscles also affect the ability to eat and swallow such that difficulty swallowing (dysphagia) can lead to aspirating food into the lungs causing aspiration pneumonia. Behavior problems can include abnormal involuntary movements, self-mutilation (such as chewing on his own fingers, lips, and tongue), and/or other compulsive behaviors. He may have irritability and uncontrolled aggressive behavior. Many of these behavior problems are associated with limited cognitive ability which most boys will have to some degree. He may develop pain and swelling of the joints (gout). Some individuals with LNS pass away suddenly and unexpectedly due to unknown causes.

Possible Causes

All of us have genetic material that makes us who we are. The genetic material is referred to as “chromosomes”. The gene for LNS has been found on the "X chromosome" called the HPRT1 gene. Mistakes in this gene cause LNS. Males have one X chromosome (designated in the medical literature as XY) and females have two X chromosomes (designated as XX). LNS is an X-linked recessive condition. This means that the mother has one abnormal gene on one X chromosome and one normal gene on the other X chromosome. Because she has one normal gene, she does not have LNS. However, if she passes down the abnormal gene to her son, he will be affected. Since he only has one X chromosome, he will have LNS because he does not have a second X chromosome with a normal gene to balance it out. The HPRT enzyme helps the body to get rid of uric acid. Because patients with LNS do not have enough or any HPRT enzyme, uric acid builds up in the body (hyperuricemia). When there is too much uric acid, it becomes solid (precipitates) and forms crystals. These crystals build up different parts of the body such as the joints (which causes gout) and kidneys (which causes kidney stones). The cause(s) of the neurologic and behavioral problems associated with this condition are not completely understood. However, individuals with LNS have abnormalities in an area of the brain called the basal ganglia, which may explain some of the neurologic symptoms.


LNS can be diagnosed by the symptoms described above along with blood or urine tests to look for high levels of uric acid. Confirmation is possible by genetic testing.


This condition is usually treated with a medication called allopurinol. Allopurinol combined with hydration helps prevent the overproduction of uric acid. By doing this, it decreases symptoms such as gout, kidney stones, pink or reddish colored urine, and “orange sand”; but it does not improve the neurologic and behavioral symptoms. Neurologic symptoms may be treated with anti-anxiety medications and anti-spasticity medications. Behavioral symptoms are best managed with behavior modification, which can be augmented with medications. Often, restraints to keep the child from biting him/herself or surgical extraction of teeth may be necessary to prevent self-biting.


With good medical care individuals with LNS may live into their 30’s or 40’s. Symptoms often worsen over time, however, which can lead to severe disability, complications, and sudden death.

Connect with other parents

In the spirit of community and support, Madisons Foundation offers the unique service of connecting parents of children with rare diseases. If you would like to be connected to other parents of children with this disease, please fill out this brief form.


National Institute of Neurological Disorders and Stroke
Provides a nice overview of LNS with links to other resources of information for families, as well as ongoing clinical trials.

Medline plus
Useful information about LNS for patients, families, and healthcare professionals.

Family Village
A great weblink with information about the syndrome as well as links to other web resources and support groups.

Google Search for Lesch-Nyhan Syndrome

References and Sources

Harrison’s Online Gene Clinics