Abstract
Lesch-Nyhan syndrome was first described over thirty years ago. The original patient was a 4-year-old boy with neurological abnormalities as well as haematuria. Crystals in his urine were identified and confirmed to be uric acid. The massive excretion of this purine led to metabolic studies using isotopically labelled uric acid to study turnover rates. Clues to the site of the enzyme defect resulted from studies with the immunosuppressive agent azathioprine, which normally causes uric acid concentrations to fall in blood and urine but was without effect in a Lesch-Nyhan patient. A deficiency of hypoxanthine phosphoribosyltransferase (HPRT) activity explained this observation in Lesch-Nyhan patients. Subsequent studies have indicated that the degree of HPRT deficiency appears to determine the severity of the disease. Molecular studies have shown that most families carry a unique mutation. Attempts are being made to correlate the type and site of a specific mutation with a particular phenotype.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
REFERENCES
Bakay B, Nissinen E, Sweetman L, Francke U, Nyhan WL (1979) Utilization of purines by an HPRT variant in an intelligent, nonmutilative patient with features of the Lesch-Nyhan syndrome. Pediatr Res 13: 1365–1370.
Catel VW, Schmidt J (1959) Uber familiar gichtische Diathese in Verbindung mit zerebralen und renalen Symptomen bei einem Kleinkind. Dtsch Med Wochenschr 84: 2145–2147.
Davidson BL, Tarle SA, Antwerp MV, et al (1991) Identification of 17 independent mutations responsible for human hypoxanthine-guanine phosphoribosyltransferase (HPRT) deficiency. Am J Hum Genet 48: 951–958.
Ehrlich M, Wang RY-H (1981) 5-Methylcytosine in eukaryotic DNA. Science 212: 1350–1370.
Jolly DJ, Okayama H, Berg P, Esty AC, Filpula D, Bohlen GG, et al (1983) Isolation and characterization of a full length, expressible cDNA for human hypoxanthine guanine phosphoribosyl transferase. Proc Natl Acad Sci USA 80 477–481.
Lesch M, Nyhan WL (1964) A familial disorder of uric acid metabolism and central nervous system function. Am J Med 36: 561–570.
Nieto LH, Nyhan WL, Page T, et al (1985) Sindrome de Lesch-Nyhan: neuva variante con actividad de hipoxantina-guanina fosforribosil transferasa (HPRT) superior a la de la enfermedad clasica y deteccion del rasgo heterocigoto en los hematies de la portadora. Medicina Clinica (Barc) 84: 68–71.
Nyhan WL, Pesek J, Sweetman L, Carpenter DG, Carter CH (1967) Genetics of an X-linked disorder of uric acid metabolism and cerebral function. Pediatr Res 1: 5–13.
Nyhan WL, Sweetman, Carpenter DG, Carter CH, Hoefnagel D (1968) Effects of azathioprine in a disorder of uric acid metabolism and cerebral function. J Pediatr 72: 111–118.
Page T, Nyhan WL (1989) The spectrum of HPRT deficiency: an update. In Mikanagi K, Nishioka K, Kelley WN, eds. Purine and Pyrimidine Metabolism in Man — VI, Part A. New York: Plenum 1989, 129–133.
Seegmiller JE, Rosenbloom FM, Kelley WN (1967) Enzyme defect associated with a sex-linked human neurological disorder and excessive purine synthesis. Science 155: 1682–1684.
Sege-Peterson K, Chambers J, Page T, Jones OW, Nyhan WL (1992a) Characterization of mutations in phenotypic variants in hypoxanthine phosphoribosyltransferase deficiency. Hum Mol Genet 1: 427–432.
Sege-Peterson K, Nyhan WL, Page T (1992b) Lesch-Nyhan disease and HPRT deficiency. In Rosenberg RN, Prusiner SB, DiMauro S, Barchi RL, Kunkel LM, eds. The Molecular and Genetic Basis of Neurological Disease. Stoneham, MA: Butterworth-Heineman, 241–259.
Shear CS, Nyhan WL, Kirman BH, Stern J (1971) Self-mutilative behavior as a feature of the De Lange syndrome. J Pediatr 78: 506–509.
Sweetman L, Nyhan WL (1974) Incorporation of glycine-13C into uric acid. In Mamer OA, Mitchell WK, Scriver CR, eds. Application of Gas Chromatography —Mass Spectrometry to the Investigation of Human Disease, Proceedings of a Workshop. Montreal: McGill University, Montreal Children's Hospital Research Institute, 179–180.
Yang TP, Patel PI, Stout JT, Jackson LG, Hildebrand BM, Caskey CT (1984) Molecular evidence for new mutations in the HPRT locus in Lesch-Nyhan patients. Nature 310: 412–414.
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Nyhan, W.L. The recognition of Lesch-Nyhan syndrome as an inborn error of purine metabolism. J Inherit Metab Dis 20, 171–178 (1997). https://doi.org/10.1023/A:1005348504512
Issue Date:
DOI: https://doi.org/10.1023/A:1005348504512