Abstract
Summary: The patient, H.Chr.B., was among the first reported with hyperuricemia and central nervous system symptoms. He has been found to have a variant of hypoxanthine guanine phosphoribosyl transferase (HPRT; E.C.2.4.2.8) distinct from the enzyme present in patients with the Lesch-Nyhan syndrome. The patient had choreoathetosis, spasticity, dysarthric speech, and hyperuricemia. However, his intelligence was normal and he had no evidence of self-mutilation. There was no activity of HPRT in the lysates of erythrocytes and cultured fibroblasts when analyzed in the usual manner. Using a newly developed method for the study of purine metabolism in intact cultured cells, this patient was found to metabolize some 9% of 8-14C-hypoxanthine, and 90% of the isotope utilized was converted to adenine and guanine nucleotides. In contrast, cells from patients with the Lesch-Nyhan syndrome were virtually completely unable to convert hypoxanthine to nucleotides. The patient's fibroblasts were even more efficient in the metabolism of 8-14C-guanine, which was utilized to the extent of 27%, over 80% of which was converted to guanine and adenine nucleotides. The growth of the cultured fibroblasts of this patient was intermediate in media containing hypoxanthine aminopterin thymidine (HAT), whereas the growth of Lesch-Nyhan cells was inhibited and normal cells grew normally. Similarly in 8-azaguanine, 6-thioguanine, and 8-azahypoxanthine, the growth of the patient's cells was intermediate between normal and Lesch-Nyhan cells. These observations provide further evidence for genetic heterogeneity among patients with disorders in purine metabolism involving the HPRT gene. They document that this famous patient did not have the Lesch-Nyhan syndrome.
Speculation: Self-mutilation is a uniform feature of the Lesch-Nyhan syndrome, and the phenotype includes a variant HPRT that has virtually no activity under any conditions of assay. Inherited variation of the gene that codes for the synthesis of HPRT may be considerable. Different variants may produce clinically distinct phenotypes.
Similar content being viewed by others
Article PDF
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Bakay, B., Nissinen, E., Sweetman, L. et al. Utilization of Purines by an HPRT Variant in an Intelligent, Nonmutilative Patient with Features of the Lesch-Nyhan Syndrome. Pediatr Res 13, 1365–1370 (1979). https://doi.org/10.1203/00006450-197912000-00013
Issue Date:
DOI: https://doi.org/10.1203/00006450-197912000-00013
Keywords
This article is cited by
-
Update on the Phenotypic Spectrum of Lesch-Nyhan Disease and its Attenuated Variants
Current Rheumatology Reports (2012)
-
Mechanisms for phenotypic variation in Lesch–Nyhan disease and its variants
Human Genetics (2011)
-
Reduced urinary serotonin excretion after intake of high doses of hypoxanthine
European Journal of Pediatrics (1989)
-
A case of severe hypoxanthine‐guanine phosphoribosyl transferase deficiency
Journal of Inherited Metabolic Disease (1985)