Lesch-Nyhan Syndrome

(Hypoxanthine-Guanine Phosphoribosyltransferase Deficiency or HPRT Deficiency; Lesch-Nyhan Disease)
  • Definition

    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, neurologic disability, and behavioral problems, including self-injury. This disease, which mainly affects men, is rare.
  • 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 the person's mother, who is a carrier.
  • Risk Factors

    Factors that increase your chances of developing Lesch-Nyhan syndrome include:
    • Sex: male
    • Having male family members on the mother's side of the family with Lesch-Nyhan syndrome
  • Symptoms

    The first symptom of Lesch-Nyhan syndrome may be 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:
      • 4 to 6 months—lack of muscle tone and inability to lift the head
      • 6 months—unusual arching of the back
      • 9 months—inability to crawl or stand
      • 12 months—inability to walk
      • 12+ months—spasms of the limbs and facial muscles
    • Blood in the urine
    • Pain and swelling of joints
    • Difficulty swallowing
    • Behavioral problems and self injury—occurs in all cases
    Uric Acid Deposits in Joint
    uric acid toe
    Copyright © Nucleus Medical Media, Inc.
    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, and loss of vision from eye rubbing, among others. 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. A physical exam will be done.
    Your bodily fluids may be tested. This can be done with blood tests.
  • Treatment

    There is no treatment to cure Lesch-Nyhan. However, good hydration and certain medications may help to alleviate some of its symptoms. For example:
    Medications
    The following medications may be used:
    • Allopurinol—to control excessive levels of uric acid in the body
    • Diazepam, haloperidol, or phenobarbital—to help reduce problem behaviors
    • Baclofen—to reduce muscle spasms
    Behavioral problems may also be managed with a combination of behavioral modification techniques and medication.
    S-adenosylmethionine—A single 2006 report suggests that administration of s-adenosylmethionine, a food supplement, may reduce self-mutilating behaviors in adults with this syndrome. This supplement, which is available in health food stores, is naturally synthesized by the human body and important for many bodily processes. Talk to your doctor before taking any supplements.
    With treatment, the average life expectancy is early- to mid-20s. There may be an increased risk of sudden death due to respiratory causes. However, many patients live longer with good medical and psychological care.
    With treatment, the average life expectancy is early- to mid-20s. 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 to have children.
  • RESOURCES

    National Organization of Rare Disorders http://www.rarediseases.org

    National Institute of Neurological Disorders and Stroke http://www.ninds.nih.gov

    CANADIAN RESOURCES

    AboutKidsHealth http://www.aboutkidshealth.ca

    Canadian Organization for Rare Disorders http://www.cord.ca

    References

    Glick N. Dramatic reduction in self-injury in Lesch-Nyhan disease following S-adenosylmethionine administration. J Inherit Metab Dis. 2006;29:687.

    Neychev VK, Jinnah H. Sudden death in Lesch-Nyhan disease. Dev Med Child Neurol. 2006;48:923-926.

    Torres RJ, Puig JG. Hypoxanthine-guanine phosphoribosyltransferase (HPRT) deficiency: Lesch-Nyhan syndrome. Orphanet J Rare Dis. 2007 Dec 8;2:48.

    What is Lesch-Nyhan syndrome? Genetics Home Reference website. Available at: http://ghr.nlm.nih.gov/condition/lesch-nyhan-syndrome. Published August 12, 2013. Accessed August 13, 2013.

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