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Environ Health Perspect. 2000 June; 108(Suppl 3): 409–411.
PMCID: PMC1637829
Research Article

Dopamine function in Lesch-Nyhan disease.


Lesch-Nyhan disease is a disorder of purine metabolism resulting from mutations in the gene for hypoxanthine guanine phosphoribosyl transferase on the X chromosome. It is characterized by hyperuricemia and all of its consequences, as in gout; but in addition, patients have impressive disease of the central nervous system. This includes spasticity, involuntary movements, and retardation of motor development. The behavioral phenotype is best remembered by self-injurious biting behavior with attendant destruction of tissue. The connection between aberrant metabolism of purines and these neurologic and behavioral features of the disease is not clear. Increasing evidence points to imbalance of neurotransmitters. There is increased excretion of the serotonin metabolite 5-hydroxyindoleacetic acid in the urine. There are decreased quantities and activities of a number of dopaminergic functions. Positron emission tomography scanning has indicated deficiency in the dopamine transporter.

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Selected References

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  • Nyhan WL, Johnson HG, Kaufman IA, Jones KL. Serotonergic approaches to the modification of behavior in the Lesch-Nyhan Syndrome. Appl Res Ment Retard. 1980;1(1-2):25–40. [PubMed]
  • 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):1568–1572. [PubMed]
  • Lloyd KG, Hornykiewicz O, Davidson L, Shannak K, Farley I, Goldstein M, Shibuya M, Kelley WN, Fox IH. Biochemical evidence of dysfunction of brain neurotransmitters in the Lesch-Nyhan syndrome. N Engl J Med. 1981 Nov 5;305(19):1106–1111. [PubMed]
  • Castells S, Chakrabarti C, Winsberg BG, Hurwic M, Perel JM, Nyhan WL. Effects of L-5-hydroxytryptophan on monoamine and amino acids turnover in the Lesch-Nyhan syndrome. J Autism Dev Disord. 1979 Mar;9(1):95–103. [PubMed]
  • Silverstein FS, Johnston MV, Hutchinson RJ, Edwards NL. Lesch-Nyhan syndrome: CSF neurotransmitter abnormalities. Neurology. 1985 Jun;35(6):907–911. [PubMed]
  • Haas RH, Marsden DL, Capistrano-Estrada S, Hamilton R, Grafe MR, Wong W, Nyhan WL. Acute basal ganglia infarction in propionic acidemia. J Child Neurol. 1995 Jan;10(1):18–22. [PubMed]
  • Nyhan WL, Bay C, Beyer EW, Mazi M. Neurologic nonmetabolic presentation of propionic acidemia. Arch Neurol. 1999 Sep;56(9):1143–1147. [PubMed]
  • Furukawa Y, Kish SJ, Bebin EM, Jacobson RD, Fryburg JS, Wilson WG, Shimadzu M, Hyland K, Trugman JM. Dystonia with motor delay in compound heterozygotes for GTP-cyclohydrolase I gene mutations. Ann Neurol. 1998 Jul;44(1):10–16. [PubMed]
  • Niznik HB. Dopamine receptors: molecular structure and function. Mol Cell Endocrinol. 1987 Nov;54(1):1–22. [PubMed]
  • Freissmuth M, Casey PJ, Gilman AG. G proteins control diverse pathways of transmembrane signaling. FASEB J. 1989 Aug;3(10):2125–2131. [PubMed]
  • Neer EJ. Heterotrimeric G proteins: organizers of transmembrane signals. Cell. 1995 Jan 27;80(2):249–257. [PubMed]

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