Summary
Inborn errors of purine and pyrimidine metabolism manifest themselves by a variety of clinical pictures. Table I gives a list of the major presenting signs and laboratory results that should lead to further investigations to rule out or to confirm the diagnostic possibilities listed. All inborn errors of purine and pyrimidine metabolism are very rare. Their recognition is, nevertheless, important for the provision of both appropriate treatment and genetic counseling. Some of the enzyme defects are benign but several have severe, life-threatening or devastating consequences. Whereas some of the disorders are amenable to treatment, others remain beyond the presently available therapeutic possibilities.
Keywords
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
Preview
Unable to display preview. Download preview PDF.
References
Sperling O, Boer P, Persky-Brosh S, Kanarek E, de Vries A (1972) Altered kinetic property of erythrocyte phosphoribosylpyrophosphate synthetase in excessive purine production. Rev Eur Etud Clin Biol 27: 703–706
Becker MA, Losman MJ, Rosenberg AL, Mehlman I, Levinson DJ, Holmes EW (1986) Phosphoribosylpyrophosphate synthetase superactivity. A study of five patients with catalytic defects in the enzyme. Arthritis Rheum 29: 880–888
Becker MA, Puig JG, Mateos FA, Jimenez ML, Kim M, Simmonds HA (1988) Inherited superactivity of phosphoribosylpyrophosphate synthetase: association of uric acid overproduction and sensorineural deafness. Am J Med 85: 383–390
Kranen S, Keough D, Gordon RB, Emmerson BT (1985) Xanthine-containing calculi during allopurinol therapy. J Urol 133: 658–659
Jaeken J, van den Berghe G (1984) An infantile autistic syndrome characterised by the presence of succinylpurines in body fluids. Lancet 2: 1058–1061
Van den Berghe G, Jaeken J (1986) Adenylosuccinase deficiency. Adv Exp Med Biol 195A: 27–33
De Voider AG, Jaeken J, van den Berghe G, Bol A, Michel C et al. (1988) Regional brain glucose utilization in adenylosuccinase-deficient patients measured by positron emission tomography. Pediatr Res 24: 238–242
Jaeken J, Wadman SK, Duran M, van Sprang FJ, Beemer FA et al. (1988) Adenylosuccinase deficiency: an inborn error or purine nucleotide synthesis. Eur J Pediatr 148: 126–131
De Bree PK, Wadman SK, Duran M, Fabery de Jonge H (1986) Diagnosis of inherited adenylosuccinase deficiency by thin-layer chromatography of urinary imidazoles and by automated cation exchange column chromatography of purines. Clin Chim Acta 156: 279–288
Laikind PK, Seegmiller JE, Gruber HE (1986) Detection of 5’-phosphoribosyl-4-(N-succinylcarboxamide)-5-aminoimidazole in urine by use of the Bratton Marshall reaction: identification of patients deficient in adenylosuccinate lyase activity. Anal Biochem 156: 81–90
Lowenstein JM (1972) Ammonia production in muscle and other tissues: the purine nucleotide cycle. Physiol Rev 52: 382–414
Flanagan WF, Holmes EW, Sabina RL, Swain JL (1986) Importance of purine nucleotide cycle to energy production in skeletal muscle. Am J Physiol 251: C795 - C802
Hers HG, van den Berghe G (1979) Enzyme defect in primary gout. Lancet 1: 585–586
Van den Berghe G, Hers HG (1980) Abnormal AMP deaminase in primary gout. Lancet 2: 1090
Ogasawara N, Goto H, Yamada Y, Nishigaki I, Itoh T, Hasegawa I (1984) Complete deficiency of AMP deaminase in human erythrocytes. Biochem Biophys Res Commun 122: 1344–1349
Fishbein WN, Armbrustmacher VW, Griffin JL (1978) Myoadenylate deaminase deficiency: a new disease of muscle. Science 200: 545–548
Shumate JB, Katnik R, Ruiz M, Kaizer K, Frieden C et al (1979) Myoadenylate deaminase deficiency. Muscle Nerve 2: 213–216
Mercelis R, Martin JJ, de Barsy T, van den Berghe G (1987) Myoadenylate deaminase deficiency: absence of correlation with exercise intolerance in 452 muscle biopsies. J Neurol 234: 385–389
Patten BM (1982) Beneficial effect of D-ribose in patient with myoadenylate deaminase deficiency. Lancet 1: 1071
Mitchell BS, Kelley WN (1980) Purinogenic immunodeficiency diseases: clinical features and molecular mechanisms. Ann Intern Med 92: 826–831
Hirschhorn R (1983) Genetic deficiencies of adenosine deaminase and purine nucleoside phosphorylase: overview, genetic heterogeneity and therapy. Birth Defects 19: 73–81
Valentine WN, Paglia DE, Tartaglia AP, Gilsanz F (1977) Hereditary hemolytic anemia with increased red cell adenosine deaminase (45- to 70-fold) and decreased adenosine triphosphate. Science 195: 783–785
Giblett ER, Anderson JE, Cohen F, Pollara B, Meuwissen HJ (1972) Adenosine-deaminase deficiency in two patients with severely impaired cellular immunity. Lancet 2: 1067–1069
Fischer A, Friedrich W, Levinsky R, Vossen J, Griscelli C et al (1986) Bone-marrow transplantation for immunodeficiencies and osteopetrosis: European survey, 1968–1985. Lancet 2: 1080–1084
Marker(ML, Hershfield MS, Schiff RI, Buckley RH (1987) Adenosine deaminase and purine nucleoside phosphorylase deficiencies: evaluation of therapeutic interventions in eight patients. J Clin Immunol 7: 389–399
Hershfield MS, Buckley RH, Greenberg ML, Melton AL, Schiff R et al (1987) Treatment of adenosine deaminase deficiency with polyethylene glycol-modified adenosine deaminase. N Engl J Med 316: 589–596
Williamson AP, Montgomery JR, South MA, Wilson R (1977) A special report: four-year study of a boy with combined immune deficiency maintained in strict reverse isolation from birth. Pediatr Res 11: 63–89
Giblett ER, Ammann AJ, Wara DW, Sandman R, Diamond LK (1975) Nucleoside phosphorylase deficiency in a child with severely defective T-cell immunity and normal B-cell immunity. Lancet 1: 1010–1013
Staal GEJ, Stoop JW, Zegers BJM, Siegenbeek van Heukelom LH, van der Vlist MJM et al (1980) Erythrocyte metabolism in purine nucleoside phosphorylase deficiency after enzyme replacement therapy by infusion of erythrocytes. J Clin Invest 65: 103–108
Dent CE, Philpot GR (1954) Xanthinuria, an inborn error (or deviation) of metabolism. Lancet 1: 182–185
Wadman SK, Duran M, Beemer FA, Cats BP, Johnson JL et al (1983) Absence of hepatic molybdenum cofactor: an inborn error of metabolism leading to a combined deficiency of sulphite oxidase and xanthine dehydrogenase. J Inherited Metab Dis 6 Suppl 1: 78–83
Shih VE, Abroms IF, Johnson JL, Carney M, Mandell R et al (1977) Sulfite oxidase deficiency. Biochemical and clinical investigations of a hereditary metabolic disorder in sulfur metabolism. N Engl J Med 297: 1022–1028
Endres W, Shin YS, Günther R, Ibel H, Duran M, Wadman SK (1988) Report on a new patient with combined deficiencies of sulphite oxidase and xanthine dehydrogenase due to molybdenum cofactor deficiency. Eur J Pediatr 148: 246–249
Lloyd KG, Hornykiewicz O, Davidson L, Shannak K, Farley I et al (1981) Biochemical evidence of dysfunction of brain neurotransmitters in the Lesch-Nyhan syndrome. N Engl J Med 305: 1106–1111
Lesch M, Nyhan WL (1964) A familial disorder of uric acid metabolism and central nervous system dysfunction. Am J Med 36: 561–570
Kelley WN, Greene ML, Rosenbloom FM, Henderson JF, Seegmiller JE (1969) Hypoxanthine-guanine phosphoribosyltransferase deficiency in gout. Ann Intern Med 70: 155–206
Kaufman JM, Greene ML, Seegmiller JE (1968) Urine uric acid to creatinine ratio. A screening test for inherited disorders of purine metabolism. Phosphoribosyltransferase ( PRT) deficiency in X-linked cerebral palsy and in a variant of gout. J Pediatr 73: 583–592
Holland PC, Dillon MJ, Pincott J, Simmonds HA, Barratt TM (1983) Hypoxanthine guanine phosphoribosyl transferase deficiency presenting with gout and renal failure in infancy. Arch Dis Child 58: 831–833
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
Page T, Bakay B, Nissinen E, Nyhan WL (1981) Hypoxanthine-guanine phosphoribosyltransferase variants: correlation of clinical phenotype with enzyme activity. J Inherited Metab Dis 4: 203–206
Watts RWE, McKeran RO, Brown E, Andrews TM, Griffiths MI (1974) Clinical and biochemical studies on treatment of Lesch-Nyhan syndrome. Arch Dis Child 49: 693–702
Nyhan WL, Parkman R, Page T, Gruber HE, Pyati J et al (1986) Bone marrow transplantation in Lesch-Nyhan disease. Adv Exp Med Biol 195A: 167–170
Wilson JM, Stout JT, Palella TD, Davidson BL, Kelley WN, Caskey CT (1986) A molecular survey of hypoxanthine-guanine phosphoribosyltranferase deficiency in man. J Clin Invest 77: 188–195
Cartier P, Hamet M (1974) Une nouvelle maladie métabolique: le déficit complet en adénine-phosphoribosyltransférase avec lithiase de 2,8-dihydroxyadénine. C R Acad Sci [D] (Paris) 279: 883–886
Van Acker KJ, Simmonds HA, Potter C, Cameron JS (1977) Complete deficiency of adenine phosphoribosyltransferase. Report of a family. N Engl J Med 297: 127–132
Greenwood MC, Dillon MJ, Simmonds HA, Barratt TM, Pincott JR, Metreweli C (1982) Renal failure due to 2,8-dihydroxyadenine urolithiasis. Eur J Pediatr 138: 346–349
Kamatani N, Terai C, Kuroshima S, Nishioka K, Mikanagi K (1987) Genetic and clinical studies on 19 families with adenine phosphoribosyltransferase deficiencies. Hum Genet 75: 163–168
Fujimori S, Akaoka I, Sakamoto K, Yamanaka H, Nishioka K, Kamatani N (1985) Common characteristics of mutant adenine phosphoribosyltransferases from four separate Japanese families with 2,8-dihydroxyadenine urolithiasis associated with partial enzyme deficiencies. Hum Genet 71: 171–176
Hidaka Y, Tarlé SA, Fujimori S, Kamatani N, Kelley WN, Palella TD (1988) Human adenine phosphoribosyltransferase deficiency. Demonstration of a single mutant allele common to the Japanese. J Clin Invest 81: 945–950
Valentine WN, Fink K, Paglia DE, Harris SR, Adams WS (1974) Hereditary hemolytic anemia with human erythrocyte pyrimidine 5’-nucleotidase deficiency. J Clin Invest 54: 866–879
Smith LH (1973) Pyrimidine metabolism in man. N Engl J Med 288: 764–771
Huguley CM, Bain JA, Rivers SL, Scoggins RB (1959) Refractory megloblastic anemia associated with excretion of orotic acid. Blood 14: 615–634
Rogers LE, Warford LR, Patterson RB, Porter FS (1968) Hereditary orotic aciduria. I. A new case with family studies. Pediatrics 42: 415–422
Winkler JK, Suttle DP (1988) Analysis of UMP synthase gene and mRNA structure in hereditary orotic aciduria fibroblasts. Am J Hum Genet 43: 86–94
Berger R, Stoker-de Vries SA, Wadman SK, Duran M, Beemer FA et al (1984) Dihydropyrimidine dehydrogenase deficiency leading to thymine-uraciluria. An inborn error of pyrimidine metabolism. Clin Chim Acta 141: 227–234
Tuchman M, Stoeckeler JS, Kiang DT, O’Dea RF, Ramnaraine ML, Mirkin BL (1985) Familial pyrimidinemia and pyrimidinuria associated with severe fluorouracil toxicity. N Engl J Med 313: 245–249
Wilcken B, Hammond J, Berger R, Wise G, James C (1985) Dihydropyrimidine dehydrogenase deficiency. A further case. J Inherited Metab Dis 8 Suppl 2: 115–116
Diasio RB, Beavers TL, Carpenter JT (1988) Familial deficiency of dihydropyrimidine dehydrogenase. Biochemical basis for familial pyrimidinemia and severe 5-fluorouracilinduced toxicity. J Clin Invest 81: 47–51
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 1990 Springer-Verlag Berlin Heidelberg
About this chapter
Cite this chapter
van den Berghe, G. (1990). Disorders of Purine and Pyrimidine Metabolism. In: Fernandes, J., Saudubray, JM., Tada, K. (eds) Inborn Metabolic Diseases. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-662-02613-7_35
Download citation
DOI: https://doi.org/10.1007/978-3-662-02613-7_35
Publisher Name: Springer, Berlin, Heidelberg
Print ISBN: 978-3-662-02615-1
Online ISBN: 978-3-662-02613-7
eBook Packages: Springer Book Archive