Abstract
Deficiencies of HPRT are usually associated with increased concentrations of PRPP and increased levels of APRT activity in erythrocytes. We report the case of a male with a partial deficiency of HPRT in whom these two parameters were normal. The clinical features of this patient were those associated with severe hyperuricaemia and gout. Studies of intact erythrocytes showed rates of incorporation of [14C]hypoxanthine and of [14C]adenine into purine nucleotides which were almost indistinguishable from normal. However, HPRT activity in erythrocyte lysates was only 9% of normal. In cell extracts of cultured lymphoblasts, the HPRT activity was 20% of control values and the APRT activity was normal. The PRPP concentration and the rate ofde novo purine synthesis in cultured lymphoblasts were both intermediate between controls and lymphoblasts from patients with the Lesch-Nyhan syndrome.
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Dean, B. M., Perrett, D., Simmonds, H. A., Sahota, A. and Van Acker, K. J. Adenine and adenosine metabolism in intact erythrocytes deficient in adenosine monophosphate-pyrophosphate phosphoribosyltransferase: a study of two families.Clin. Sci. Mol. Med. 55 (1978) 407–412
Emmerson, B. T., Gordon, R. B. and Johnson, L. A. Urate kinetics in hypoxanthine-guanine phosphoribosyltransferase deficiency: their significance for the understanding of gout.Quart. J. Med. 45 (1976) 49–61
Emmerson, B. T., Thompson, C. J. and Wallace, D. C. Partial deficiency of hypoxanthine-guanine phosphoribosyltransferase: intermediate enzyme deficiency in heterozygote red cells.Ann. Intern. Med. 76 (1972) 285–287
Emmerson, B. T. and Thompson, L. The spectrum of hypoxanthine-guanine phosphoribosyltransferase deficiency.Quart. J. Med. 42 (1973) 423–440
Gordon, R. B., Counsilman, A. C., Cross, S. M. and Emmerson, B. T. Purine synthesisde novo in lymphocytes from patients with gout.Clin. Sci. 63 (1982) 429–435
Gordon, R. B., Thompson, L. and Emmerson, B. T. Erythrocyte phophoribosylpyrophosphate concentrations in heterozygotes for hypoxanthine-guanine phosphoribosyltransferase deficiency.Metabolism 23 (1974) 921–927
Gordon, R. B., Thompson, L. and Emmerson, B. T. Partial HPRT deficiency: heterozygotes exhibit one cell population in intact cell assays. In Muller, M. M., Kaiser, E. and Seegmiller, J. E. (eds.)Adv. Exp. Med. Biol. 76A, Plenum Press, New York, 1977, pp. 314–318
Gordon, R. B., Thompson, L., Johnson, L. A. and Emmerson, B. T. Regulation of purinede novo synthesis in cultured human fibroblasts: the role of P-ribose-PP.Biochim. Biophys. Acta 562 (1979) 162–176
Greene, M. L., Boyle, J. R. and Seegmiller, J. E. Substrate stabilisation: genetically controlled reciprocal relationship of two human enzymes.Science 167 (1970) 887–889
Gutensohn, W. and Jahn, H. Partial deficiency of hypoxanthine-phosphoribosyltransferase: evidence for a structural mutation in a patient with gout.Eur. J. Clin. Invest. 9 (1979) 43–47
Henderson, J. F. Purine metabolism in mammalian cells.Biochem. Soc. Trans. 3 (1976) 1195–1198
Hershko, A., Razin, A. and Mager, J. Regulation of the synthesis of 5-phosphoribosyl-1-pyrophosphate in intact red blood cells and in cell-free preparations.Biochim. Biophys. Acta 184 (1969) 64–76
Kelley, W. N., Greene, M. L., Rosenbloom, F. M., Henderson, J. F. and Seegmiller, J. E. Hypoxanthine-guanine phosphoribosyltransferase deficiency in gout.Ann. Int. Med. 70 (1969) 155–206
Kelley, W. N. Biochemistry of the X-linked uric aciduria-enzyme defect and its genetic variants.Arch. Intern. Med. 130 (1972) 199–206
Kelley, W. N. Studies on the adenine phosphoribosyltransferase enzyme in human fibroblasts lacking hypoxanthine-guanine phosphoribosyltransferase.J. Lab. Clin. Med. 77 (1971) 33
Lesch, M. and Nyhan, W. L. A familial disorder of uric acid metabolism and central nervous system function.Am. J. Med. 36 (1964) 561–570
Liddle, L., Seegmiller, J. E. and Laster, L. The enzymatic spectrophotometric method for determination of uric acid.J. Lab. Clin. Med. 54 (1959) 903
Losman, M. J., Hecker, S., Woo, S. and Becker, M. A. Diagnostic evaluation of phosphoribosylpyrophosphate synthetase activities in hemolysates.J. Lab. Clin. Med. 103 (1984) 932–943
Rubin, C. S., Balis, M. E., Piomelli, S., Berman, P. H. and Dancis, J. Elevated AMP pyrophosphorylase activity in congenital IMP pyrophosphorylase deficiency (Lesch-Nyhan disease).J. Lab. Clin. Med. 74 (1969) 732–741
Sperling, O., Eilam, G., Persky-Brosh, S. and De Vries, A. Simpler method for the determination of 5-phosphoribosyl-1-pyrophosphate in red blood cells.J. Lab. Clin. Med. 79 (1972) 1021–1026
Wilson, J. M., Daddona, P. E., Otoadese, T., and Kelley, W. N. Adenine phosphoribosyltransferase in patients with disorders of purine and pyrimidine metabolism.J. Lab. Clin. Med. 99 (1982) 163–174
Yip, L. C., Dancis, J. and Balis, M. E. Immunochemical studies of AMP: pyrophosphate phosphoribosyltransferase from normal and Lesch-Nyhan subjects.Biochim. Biophys. Acta 293 (1973) 359–369
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Gordon, R.B., Keough, D.T. & Emmerson, B.T. HPRT-Deficiency associated with normal PRPP concentration and APRT activity. J Inherit Metab Dis 10, 82–88 (1987). https://doi.org/10.1007/BF01799493
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DOI: https://doi.org/10.1007/BF01799493