Lesch-Nyhan syndrome is a genetic disorder. It affects the metabolism of purines in the body. Purines are protein molecules that are important for the metabolism of RNA and DNA, which make up our genetic codes. Lesch-Nyhan syndrome is characterized by uric acid build-up and self-injury. It occurs mainly in males. This disease is rare; it occurs in 1 of every 100,000 males.
Causes
Lesch-Nyhan syndrome is caused by a mutation or change in a gene. This change results in the absence of the enzyme hypoxanthine-guanine phosphoribosyltransferase (HPRT). HPRT is needed to metabolize uric acid. Without this enzyme, uric acid builds up in the central nervous system, kidneys, and other areas of the body.
This gene mutation occurs on the X chromosome. It can either be a new mutation in the affected person or inherited from his mother, who is a carrier.
Risk Factors
A risk factor is something that increases your chances of getting a disease or condition. Risk factors for developing Lesch-Nyhan syndrome include:
Symptoms
The first symptom of Lesch-Nyhan syndrome is orange-colored crystal-like deposits in the diaper. This may occur in children as young as three months. These deposits are caused by increased uric acid in the urine. Other symptoms include:
-
Irritability
-
Nervous system impairment:
-
-
-
-
-
-
Kidney stones
-
Blood in the urine
-
Pain and swelling of joints
-
Difficulty swallowing (dysphagia)
-
Impaired kidney function
-
Self-injury
Self-Injury
Self-mutilating behavior is the hallmark of this disease. Children begin to bite their fingers, lips, and the insides of their mouths as early as two years old.
As children grow, self-injury becomes increasingly compulsive and severe. Eventually, mechanical physical restraints will be necessary to prevent head and leg banging, nose gouging, loss of fingers and lips from biting, loss of vision from eye rubbing, etc. In addition to self-injury, older children and teens will become physically and verbally aggressive.
The cause of these behaviors is not entirely understood. However, some experts believe it is related to abnormalities in brain chemicals called neurotransmitters. It should be stressed that the child does not want to hurt himself or others, but is incapable of preventing these behaviors. People with Lesch-Nyhan syndrome have been described as “doing the opposite” of what they really want.
Diagnosis
The doctor will ask about symptoms, behavior traits, and medical history, and perform a physical exam. Tests may include:
-
Measurement of HPRT enzyme activity–to confirm the diagnosis
-
Molecular genetic testing of the HPRT1 gene–to confirm the diagnosis and to detect if an unaffected female is a carrier of the gene mutation
Treatment
There is no treatment to cure Lesch-Nyhan. However, certain medications may help to alleviate some of its symptoms. For example:
With treatment, the average life expectancy is early- to mid-20s, and there may be an increased risk of sudden death due to respiratory causes. However, many patients live longer with good medical and psychological care.
Prevention
There are no guidelines to prevent Lesch-Nyhan syndrome. If you have a family history of this condition, you can talk to a genetic counselor when deciding whether or not to have children.
RESOURCES:
International Lesch-Nyhan Disease Association
11402 Ferndale St.
Philadelphia, PA 19116
Phone: 215-677-4206
Lesch-Nyhan Syndrome Children's Research Foundation
210 South Green Bay Road
.Lake Forest, IL 60045
Phone: 847-234-3154
The Matheny Institute for Research in Developmental Disabilities
http://www.matheny.org
National Institute of Neurological Disorders and Stroke
http://www.ninds.nih.gov
References:
Glick N. Dramatic reduction in self-injury in Lesch-Nyhan disease following S-adenosylmethionine administration. J Inherit Metab Dis. 2006 Oct;29(5):687.
Lesch-Nyhan Disease National Registry . New York University School of Medicine, Department of Psychiatry.
Lesch-Nyhan syndrome. GeneTests, GeneClinics: Medical Genetics Information Resource (database online). University of Washington and Children's Health System, Seattle; 1993-2002 (updated weekly). Available at http://www.genetests.org. Accessed June 2002.
National Institute of Neurological Disorders and Stroke website. Available at: http://www.ninds.nih.gov.
The National Library of Medicine website. Available at: http://www.nlm.nih.gov.
New York University School of Medicine website. Available at: http://www.med.nyu.edu/.
Neychev VK, Jinnah H. Sudden death in Lesch-Nyhan disease. Dev Med Child Neurol. 2006 Nov;48(11):923-6.
The Purine Research Society website. Available at: http://www.purineresearchsociety.org/.
