부산대학교 도서관

BACKGROUND: Lesch-Nyhan disease is an inborn error of purine metabolism that results from deficiency of the activity of hypoxanthine phosphoribosyltransferase (HPRT). In the classic disease, the activity of the enzyme is completely deficient; the patient has mental retardation, spasticity, dystonia, and self-injurious behavior, as well as elevated concentrations of uric acid in blood and urine and its consequences of nephropathy, urinary tract calculi, and tophaceous gout. The HPRT gene is located on the X chromosome, and its expression is usually X-linked recessive. There are variant HPRT enzymes with some activity, and milder clinical expression, but the rule has been that each mutation produces a stereotypical pattern of clinical disease. OBJECTIVE: To document a family in which a single mutation has led to 3 different phenotypes in 5 individuals. DESIGN: Case reports. SETTINGS: A foundation devoted to the investigation and care of patients with rare diseases and a university-based biochemical genetics laboratory. MAIN OUTCOME MEASURES: Clinical and biochemical observations of predominantly 1 generation of a family. RESULTS: A mutation (IVS6 + 2) led to deletion of exon 6. In 1 patient, the phenotype was that of classic Lesch-Nyhan syndrome, while the patientʼs brother and uncle had a much milder disease, which was difficult to distinguish from good health; 2 cousins had an intermediate phenotype. CONCLUSION: It is no longer true that a given mutation in the HPRT gene will lead to a reproducible pattern of clinical expression.