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Lesch-Nyhan syndrome

Reviewed December 2007

What is Lesch-Nyhan syndrome?

Lesch-Nyhan syndrome is a condition characterized by the overproduction and accumulation of uric acid, a waste product of normal chemical processes that is found in blood and urine. The overproduction of uric acid can cause gouty arthritis (arthritis caused by an accumulation of uric acid in the joints), kidney stones, and bladder stones. Problems with the nervous system and behavioral disturbances are also characteristic of this disorder. Abnormal involuntary muscle movements such as flexing, jerking, and flailing are often displayed by people affected with this disorder. People with Lesch-Nyhan syndrome usually cannot walk, require assistance sitting, and are generally wheelchair-bound. Self-injury, including biting and head banging, is the most common and distinctive behavioral problem in those with Lesch-Nyhan syndrome.

How common is Lesch-Nyhan syndrome?

The prevalence of Lesch-Nyhan syndrome is approximately 1 in 380,000 individuals. This condition occurs with a similar frequency in all populations.

What genes are related to Lesch-Nyhan syndrome?

Mutations in the HPRT1 gene cause Lesch-Nyhan syndrome.

Mutations in the HPRT1 gene cause a severe deficiency of the enzyme hypoxanthine phosphoribosyltransferase 1. This enzyme is responsible for recycling purines, a type of building block of DNA and its chemical cousin RNA. When this enzyme is lacking, the breakdown of purines results in abnormally high levels of uric acid in the body. It is unclear how a shortage of this enzyme causes the neurological and behavioral problems characteristic of Lesch-Nyhan syndrome.

Related Gene(s)

Changes in this gene are associated with Lesch-Nyhan syndrome.

  • HPRT1

How do people inherit Lesch-Nyhan syndrome?

This condition is inherited in an X-linked recessive pattern. The gene associated with this condition is located on the X chromosome, which is one of the two sex chromosomes. In males (who have only one X chromosome), one altered copy of the gene in each cell is sufficient to cause the condition. In females (who have two X chromosomes), a mutation would have to occur in both copies of the gene to cause the disorder. Because it is unlikely that females will have two altered copies of this gene, males are affected by X-linked recessive disorders much more frequently than females. A characteristic of X-linked inheritance is that fathers cannot pass X-linked traits to their sons.

Where can I find information about diagnosis or management of Lesch-Nyhan syndrome?

These resources address the diagnosis or management of Lesch-Nyhan syndrome and may include treatment providers.

  • Gene Review: Lesch-Nyhan Syndrome (http://www.ncbi.nlm.nih.gov/bookshelf/br.fcgi?book=gene&part=lns)
  • Gene Tests: Lesch-Nyhan Syndrome (http://www.ncbi.nlm.nih.gov/sites/GeneTests/lab/clinical_disease_id/2356)
  • MedlinePlus Encyclopedia: Lesch-Nyhan Syndrome (http://www.nlm.nih.gov/medlineplus/ency/article/001655.htm)
  • MedlinePlus Encyclopedia: Uric Acid Crystals (http://www.nlm.nih.gov/medlineplus/ency/imagepages/1222.htm)

You might also find information on the diagnosis or management of Lesch-Nyhan syndrome in Educational resources (http://ghr.nlm.nih.gov/condition/lesch-nyhan-syndrome/show/Educational+resources) and Patient support (http://ghr.nlm.nih.gov/condition/lesch-nyhan-syndrome/show/Patient+support).

To locate a healthcare provider, see How can I find a genetics professional in my area? (http://ghr.nlm.nih.gov/handbook/consult/findingprofessional) in the Handbook.

Where can I find additional information about Lesch-Nyhan syndrome?

You may find the following resources about Lesch-Nyhan syndrome helpful. These materials are written for the general public.

  • MedlinePlus - Health information

    • Encyclopedia: Lesch-Nyhan Syndrome (http://www.nlm.nih.gov/medlineplus/ency/article/001655.htm)
    • Encyclopedia: Uric Acid Crystals (http://www.nlm.nih.gov/medlineplus/ency/imagepages/1222.htm)
    • Health Topic: Genetic Brain Disorders (http://www.nlm.nih.gov/medlineplus/geneticbraindisorders.html)
    • Health Topic: Gout (http://www.nlm.nih.gov/medlineplus/gout.html)
    • Health Topic: Neurologic Diseases (http://www.nlm.nih.gov/medlineplus/neurologicdiseases.html)

  • Additional NIH Resources - National Institutes of Health

    • National Center for Biotechnology Information: Genes and Disease (http://www.ncbi.nlm.nih.gov/books/bv.fcgi?call=bv.View..ShowSection&rid=gnd.section.298)
    • NINDS Lesch-Nyhan Syndrome Information Page (http://www.ninds.nih.gov/disorders/lesch_nyhan/lesch_nyhan.htm)

  • Educational resources - Information pages

    • Madisons Foundation (http://www.madisonsfoundation.org/index.php?option=com_mpower&task=disease&diseaseID=287)
    • Orphanet (http://www.orpha.net/consor/cgi-bin/OC_Exp.php?Lng=EN&Expert=510)

  • Patient support - For patients and families

    • Family Village (http://www.familyvillage.wisc.edu/lib_lnd.htm)
    • Lesch-Nyhan Disease International Study Group (http://www.lesch-nyhan.org/)
    • National Organization for Rare Disorders (http://www.rarediseases.org/rare-disease-information/rare-diseases/byID/255/viewAbstract)
    • Resource list from the University of Kansas Medical Center (http://www.kumc.edu/gec/support/lesch.html)

You may also be interested in these resources, which are designed for healthcare professionals and researchers.

  • Gene Reviews - Clinical summary (http://www.ncbi.nlm.nih.gov/bookshelf/br.fcgi?book=gene&part=lns)
  • Gene Tests - DNA tests ordered by healthcare professionals (http://www.ncbi.nlm.nih.gov/sites/GeneTests/lab/clinical_disease_id/2356)
  • ClinicalTrials.gov - Linking patients to medical research (http://clinicaltrials.gov/ct2/results?cond=%22lesch-nyhan%20syndrome%22)
  • PubMed - Recent literature (http://www.ncbi.nlm.nih.gov/pubmed?term=(Lesch-Nyhan%20Syndrome%5BMAJR%5D)%20AND%20(Lesch-Nyhan%20syndrome%5BTIAB%5D)%20AND%20english%5Bla%5D%20AND%20human%5Bmh%5D%20AND%20%22last%201800%20days%22%5Bdp%5D)
  • Online Books - Medical and science texts
    Scriver's Online Metabolic and Molecular Bases of Inherited Disease (OMMBID): Lesch-Nyhan Disease and Its Variants (http://books.mcgraw-hill.com/getommbid.php?isbn=0071459960&template=ommbid&c=107)

  • OMIM - Genetic disorder catalog

    • KELLEY-SEEGMILLER SYNDROME (http://omim.org/entry/300323)
    • LESCH-NYHAN SYNDROME (http://omim.org/entry/300322)

What other names do people use for Lesch-Nyhan syndrome?

  • Choreoathetosis self-mutilation syndrome
  • Complete HPRT deficiency
  • Complete hypoxanthine-guanine phosphoribosyltransferase deficiency
  • Deficiency of guanine phosphoribosyltransferase
  • Deficiency of hypoxanthine phosphoribosyltransferase
  • hypoxanthine-guanine phosphoribosyltransferase (HGPRT) deficiency
  • Juvenile gout, choreoathetosis, mental retardation syndrome
  • Juvenile hyperuricemia syndrome
  • Lesch-Nyhan Disease
  • LNS
  • Primary hyperuricemia syndrome
  • Total HPRT deficiency
  • Total hypoxanthine-guanine phosphoribosyl transferase deficiency
  • X-linked hyperuricemia
  • X-linked primary hyperuricemia
  • X-linked uric aciduria enzyme defect

For more information about naming genetic conditions, see the Genetics Home Reference Condition Naming Guidelines (http://ghr.nlm.nih.gov/ConditionNameGuide) and How are genetic conditions and genes named? (http://ghr.nlm.nih.gov/handbook/mutationsanddisorders/naming) in the Handbook.

What if I still have specific questions about Lesch-Nyhan syndrome?

Ask the Genetic and Rare Diseases Information Center (http://rarediseases.info.nih.gov/GARD/).

What glossary definitions help with understanding Lesch-Nyhan syndrome?

acids ; aciduria ; arthritis ; cell ; chromosome ; deficiency ; DNA ; enzyme ; gene ; gout ; guanine ; inheritance ; injury ; involuntary ; joint ; juvenile ; kidney ; kidney stones ; mental retardation ; mutation ; nervous system ; neurological ; population ; prevalence ; purines ; recessive ; RNA ; sex chromosomes ; stone ; syndrome ; trait ; transferase ; uric acid ; X-linked recessive

You may find definitions for these and many other terms in the Genetics Home Reference Glossary (http://ghr.nlm.nih.gov/glossary).

References

  • Deutsch SI, Long KD, Rosse RB, Mastropaolo J, Eller J. Hypothesized deficiency of guanine-based purines may contribute to abnormalities of neurodevelopment, neuromodulation, and neurotransmission in Lesch-Nyhan syndrome. Clin Neuropharmacol. 2005 Jan-Feb;28(1):28-37. Review. (http://www.ncbi.nlm.nih.gov/pubmed/15711436?dopt=Abstract)
  • Ernst M, Zametkin AJ, Matochik JA, Pascualvaca D, Jons PH, Hardy K, Hankerson JG, Doudet DJ, Cohen RM. Presynaptic dopaminergic deficits in Lesch-Nyhan disease. N Engl J Med. 1996 Jun 13;334(24):1568-72. (http://www.ncbi.nlm.nih.gov/pubmed/8628337?dopt=Abstract)
  • Jinnah HA, De Gregorio L, Harris JC, Nyhan WL, O'Neill JP. The spectrum of inherited mutations causing HPRT deficiency: 75 new cases and a review of 196 previously reported cases. Mutat Res. 2000 Oct;463(3):309-26. Review. (http://www.ncbi.nlm.nih.gov/pubmed/11018746?dopt=Abstract)
  • Jinnah HA, Visser JE, Harris JC, Verdu A, Larovere L, Ceballos-Picot I, Gonzalez-Alegre P, Neychev V, Torres RJ, Dulac O, Desguerre I, Schretlen DJ, Robey KL, Barabas G, Bloem BR, Nyhan W, De Kremer R, Eddey GE, Puig JG, Reich SG; Lesch-Nyhan Disease International Study Group. Delineation of the motor disorder of Lesch-Nyhan disease. Brain. 2006 May;129(Pt 5):1201-17. Epub 2006 Mar 20. Review. (http://www.ncbi.nlm.nih.gov/pubmed/16549399?dopt=Abstract)
  • Nyhan WL, Wong DF. New approaches to understanding Lesch-Nyhan disease. N Engl J Med. 1996 Jun 13;334(24):1602-4. (http://www.ncbi.nlm.nih.gov/pubmed/8628345?dopt=Abstract)
  • Nyhan WL. Dopamine function in Lesch-Nyhan disease. Environ Health Perspect. 2000 Jun;108 Suppl 3:409-11. Review. (http://www.ncbi.nlm.nih.gov/pubmed/10852837?dopt=Abstract)
  • Nyhan WL. The recognition of Lesch-Nyhan syndrome as an inborn error of purine metabolism. J Inherit Metab Dis. 1997 Jun;20(2):171-8. Review. (http://www.ncbi.nlm.nih.gov/pubmed/9211189?dopt=Abstract)
  • OMIM: LESCH-NYHAN SYNDROME (http://omim.org/entry/300322)
  • Puig JG, Torres RJ, Mateos FA, Ramos TH, Arcas JM, Buño AS, O'Neill P. The spectrum of hypoxanthine-guanine phosphoribosyltransferase (HPRT) deficiency. Clinical experience based on 22 patients from 18 Spanish families. Medicine (Baltimore). 2001 Mar;80(2):102-12. (http://www.ncbi.nlm.nih.gov/pubmed/11307586?dopt=Abstract)
  • Saito Y, Takashima S. Neurotransmitter changes in the pathophysiology of Lesch-Nyhan syndrome. Brain Dev. 2000 Sep;22 Suppl 1:S122-31. Review. (http://www.ncbi.nlm.nih.gov/pubmed/10984673?dopt=Abstract)
  • Sculley DG, Dawson PA, Emmerson BT, Gordon RB. A review of the molecular basis of hypoxanthine-guanine phosphoribosyltransferase (HPRT) deficiency. Hum Genet. 1992 Nov;90(3):195-207. Review. (http://www.ncbi.nlm.nih.gov/pubmed/1487231?dopt=Abstract)
  • Visser JE, Bär PR, Jinnah HA. Lesch-Nyhan disease and the basal ganglia. Brain Res Brain Res Rev. 2000 Apr;32(2-3):449-75. Review. (http://www.ncbi.nlm.nih.gov/pubmed/10760551?dopt=Abstract)

 

The resources on this site should not be used as a substitute for professional medical care or advice. Users seeking information about a personal genetic disease, syndrome, or condition should consult with a qualified healthcare professional. See How can I find a genetics professional in my area? (http://ghr.nlm.nih.gov/handbook/consult/findingprofessional) in the Handbook.

 
Reviewed: December 2007
Published: May 21, 2012