Abstract
In several patients with different degrees of HPRT deficiencies, residual activities have been determined in both lysed and intact erythrocytes. No close correlation could be found between the degree of HPRT deficiency and the severity of the clinical expression. Unless HPRT activity in both intact and lysed erythrocytes was below detection level, the residual activity in intact red blood cells was higher than in lysates. Tissue-specific heterogeneity was illustrated with a patient suffering from X-linked gout. Lysates from erythrocytes, leukocytes, and cultured fibroblasts showed 1%, 8%, and 100% of normal HPRT activity, respectively. Characterization of the erythrocyte and fibroblast HPRT from this patient showed no kinetic abnormalities. However, there was a decreased heat stability. It is concluded that for a better understanding of the pathophysiology in HPRT deficiency studies on nucleated cells from the different tissues are needed.
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Arnold, W. J., Meade, J. C., and Kelley, W. N. (1972). Hypoxanthine-guanine phosphoribosyl transferase: Characteristics of the mutant enzyme in erythrocytes from patients with the Lesch-Nyhan syndrome. J. Clin. Invest. 511805.
Bakay, B., and Nyhan, W. L. (1972). Electrophoretic properties of hypoxanthine-guanine phosphoribosyl transferase in erythrocytes of subjects with Lesch-Nyhan syndrome. Biochem. Genet. 6139.
Becker, M. A., and Sweetman, L. (1975). Gout with mild hypoxanthine-guanine phosphoribosyl transferase deficiency due to diminished affinity for purine substrate (abst.). Clin. Res. 23:26A.
Benke, P. J., and Herrick, N. (1972). Azaguanine resistance as a manifestation of a new form of metabolic overproduction of uric acid. Am. J. Med. 52547.
Chow, D. C., Kawahara, F. S., Saunders, T., and Sorensen, L. B. (1970). A new assay method for hypoxanthine-guanine phosphoribosyl transferase. J. Lab. Clin. Med. 76733.
Dancis, J., Yip, L. C., Cox, R. P., Piomelli, S., and Balis, M. E. (1973). Disparate enzyme activity in erythrocytes and leucocytes: A variant of hypoxanthine phosphoribosyl transferase deficiency with an unstable enzyme. J. Clin. Invest. 522068.
de Bruyn, C. H. M. M. (1976). Hypoxanthine-guanine phosphoribosyl transferase deficiency. Hum. Genet. 31127.
de Bruyn, C. H. M. M., and Oei, T. L. (1977). Incorporation of purine bases by intact red blood cells. Adv. Exp. Med. Biol. 76B139.
de Bruyn, C. H. M. M., Oei, T. L., Geerdink, R. A., and Lommen, E. J. P. (1973). An atypical case of hypoxanthine-guanine phosphoribosyl transferase deficiency (Lesch-Nyhan syndrome). II. Genetic studies. Clin. Genet. 4353.
de Bruyn, C. H. M. M., Oei, T. L., and Hösli, P. (1976). Quantitative radiochemical enzyme assays in single cells: Purine phosphoribosyl transferase activities in cultured fibroblasts. Biochem. Biophys. Res. Commun. 68483.
Dwosh, I. L., Moore, M., and Fox, I. H. (1974). Hypoxanthine-guanine phosphoribosyl transferase deficiency: Phenotypic and genotypic heterogeneity. J. Rheumatol. 1441.
Fox, I. H., and Marchant, P. (1977). Human 5′-nucleotidase: Multiple molecular forms and regulation. Adv. Exp. Med. Biol. 76A249.
Fujimoto, W. Y., and Seegmiller, J. E. (1970). Hypoxanthine-guanine phosphoribosyl transferase deficiency: Activity in normal, mutant and heterozygote cultured human skin fibroblasts. Proc. Natl. Acad. Sci. 65577.
Geerdink, R. A., de Vries, W. H. M., Willemse, J., Oei, T. L., and de Bruyn, C. H. M. M. (1973). An atypical case of hypoxanthine-guanine phosphoribosyl transferase deficiency (Lesch-Nyhan syndrome). I. Clinical studies. Clin. Genet. 4348.
Harris, H., and Cook, P. R. (1969). Synthesis of an enzyme by an erythrocyte nucleus in a hybrid cell. J. Cell Sci. 5121.
Hatanaka, M., DelGuidice, R., and Long, C. (1975). Adenine formation from adenosine by mycoplasmas: Adenosine phosphorylase activity. Proc. Natl. Acad. Sci. 721401.
Henderson, J. F., Brox, L. W., Kelley, W. N., Rosenbloom, F. M., and Seegmiller, J. E. (1968). Kinetic studies of hypoxanthine-guanine phosphoribosyl transferase. J. Biol. Chem. 2432514.
Holland, M. J. C., Dilorenzo, A. M., Dancis, J., Balis, M. E., Yü, T. F., and Cox, R. P. (1976). Hypoxanthine phosphoribosyltransferase activity in intact fibroblasts from patients with X-linked hyperuricemia. J. Clin. Invest. 571600.
Hösli, P. (1972). Tissue cultivation on plastic films. Tecnomara A. G., Rieterstrasse 59, Postfach CH 8059, Zürich, Switzerland.
Hösli, P. (1974). Microtechniques for rapid prenatal diagnosis in early pregnancy. In Motulski, A. G., and Lentz, W. (eds.), Birth Defects Excerpta Medica, Amsterdam, pp. 226–233.
Hösli, P. (1977). Quantitative assays of enzyme activity in single cells: Early prenatal diagnosis of genetic disorders. Clin. Chem. 231476.
Hösli, P., and de Bruyn, C. H. M. M. (1977). Ultramicrochemistry: A contribution to the analysis of purine metabolism in man. Adv. Exp. Med. Biol. 76A591.
Kelley, W. N., and Meade, J. C. (1971). Studies on hypoxanthine-guanine phosphoribosyl transferase in fibroblasts from patients with the Lesch-Nyhan syndrome: Evidence for genetic heterogeneity. J. Biol. Chem. 2462553.
Kelley, W. N., Rosenbloom, F. M., Henderson, J. F., and Seegmiller, J. E. (1967). A specific enzyme defect in gout associated with overproduction of uric acid. Proc. Natl. Acad. Sci. 571735.
Lesch, M., and Nyhan, W. L. (1964). A familial disorder of uric acid metabolism and central nervous system function. Am. J. Med. 36561.
Lommen, E. J. P. (1973). Hypoxanthine-guanine phosphoribosyl transferase deficiency. Thesis, Centrale Drukkerijen, Nijmegen.
McDonald, J. A., and Kelley, W. N. (1971). Lesch-Nyhan syndrome: Altered kinetic properties of mutant enzyme. Science 171689.
Murray, A. W., and Friedrichs, B. (1969). Inhibition of 5′-nucleotidase from Ehrlich ascites tumor cells by nucleoside triphosphates. Biochem. J. 11183.
Seegmiller, J. E. (1976). Inherited deficiency of hypoxanthine-guanine phosphoribosyl transferase in X-linked uric aciduria. Adv. Hum. Genet. 675.
Seegmiller, J. E., Rosenbloom, F. M., and Kelley, W. N. (1967). Enzyme defect associated with a sex-linked human neurological disorder and excessive purine synthesis. Science 1551682.
Sperling, O., Boer, P., Eilam, G., and de Vries, A. (1972). Evidence for molecular alteration of erythrocyte hypoxanthine-guanine phosphoribosyl transferase in a gouty family with partial deficiency of the enzyme. Eur. J. Clin, Biol. Res. 1772.
Uitendaal. M. P., Oei, T. L., de Bruyn, C. H. M. M., and Hösli, P. (1976). Metabolic cooperation studied by a quantitative enzyme assay of single cells. Biochem. Biophys. Res. Commun. 71574.
Uitendaal, M. P., de Bruyn, C. H. M. M., Oei, T. L., and Hösli, P. (1978). Characterisation of purine nucleoside phosphorylase from fibroblasts using ultramicrochemical methods. Hum. Hered. 28151.
van der Zee, S. P. M. (1972). Het Lesch-Nyhan syndroom. Thesis, Schippers, Nijmegen.
van Herwaarden, C. L. A., van der Korst, J. K., Boerbooms, A. M. P., de Bruyn, C. H. M. M., and Oei, T. L. (1976). Partial hypoxanthine-guanine phosphoribosyl transferase deficiency in a “Celebesian” family. Neth. J. Med. 19272.
Yü, T. F., Balis, M. E., Krenitsky, T. A., Dancis, J., Silvers, D. N., Elion, G. B. and Gutman, A. B. (1972). Rarity of X-linked partial hypoxanthine-guanine phosphoribosyl transferase deficiency in a large gouty population. Ann. Intern. Med. 76255.
Zoref, E., Sperling, O., and de Vries, A. (1974). Stabilization by PRPP of cellular purine phosphoribosyl transferases against inactivation by freezing and thawing: Study of normal and hypoxanthine-guanine phosphoribosyl transferase deficient human fibroblasts. Adv. Exp. Med. Biol. 41A15.
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This investigation was supported by FUNGO (The Netherlands) and INSERM ATP 367668 (France) and Fondation de France.
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Uitendaal, M.P., de Bruyn, C.H.M.M., Oei, T.L. et al. Molecular and tissue-specific heterogeneity in HPRT deficiency. Biochem Genet 16, 1187–1202 (1978). https://doi.org/10.1007/BF00484539
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DOI: https://doi.org/10.1007/BF00484539