Enzymdefekte des Purinstoffwechsels mit Gicht

  • W. Löffler
  • W. Gröbner

Zusammenfassung

Die Entdeckung eines spezifischen Enzymdefekts, der zu vermehrter Harnsäurebildung führt (Kelley et al. 1967), beendete den alten Streit um die Pathogenese der Hyperurikämie. Es war damit erwiesen, daß die primäre Hyperurikämie Folge sowohl einer verminderten Ausscheidung (Thannhauser 1929) als auch einer vermehrten Bildung von Harnsäure (Gutman u. Yü 1957; Wyngaarden 1957) sein kann (Zöllner 1960).

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

Literatur

  1. Band PR, Silverberg DS, Henderson JF, Ulan RA, Wensel RH, Banerjee TK, Little AS (1970) Xanthine nephropathy in a patient with lymphosarcoma treated with allopurinol. N Engl J Med 283: 354–357.PubMedCrossRefGoogle Scholar
  2. Becker MA, Raivio KO, Bakay B, Adams WB, Nyhan WL (1980) Variant human phosphoribosylpyrophosphate synthetase altered in regulatory and catalytic functions. J Clin Invest 65: 109–120.PubMedCrossRefGoogle Scholar
  3. Becker MA, Puig JG, Mateos FA, Jimenez ML, Kim M, Simmonds HA (1988) Inherited superactivity of phophoribosylpyrophosphate synthetase: Association of uric acid overproduction and sensorineural deafness. Am J Med 85: 383–390.PubMedCrossRefGoogle Scholar
  4. Berman PH, Balis ME, Dancis J (1969) Congenital hyperuricemia, an inborn error of purine metabolism associated with psychomotor retardation, athetosis, and selfmutilation. Arch Neurol 20: 44–50.PubMedCrossRefGoogle Scholar
  5. Brock WA, Golden J, Kaplan GW (1983) Xanthine calculi in the Lesch-Nyhan syndrome. J Urol 130: 157–159.PubMedGoogle Scholar
  6. Carcassi A, Marcolongo R, Marinello E, Riario-Sforza G, Boggiano C (1969) Liver xanthine oxidase in gouty patients. Arthritis Rheum 12: 17–20.PubMedCrossRefGoogle Scholar
  7. Catel W, Schmidt J (1959) Über familiäre gichtische Diathese in Verbindung mit zerebralen und renalen Symptomen bei einem Kleinkind. Dtsch Med Wochenschr 84: 2145–2148.PubMedCrossRefGoogle Scholar
  8. Clarkson BA (1966) Uric acid related to uraemic symptoms. Proc EDTA 3: 3–7.Google Scholar
  9. Delbarre F, Auscher C, Amor B, de Gery A (1973) Gout with APRT deficiency. (Abstract) Isr J Med Sci 9: 1088.Google Scholar
  10. Demus A, Kaiser W, Schaub J (1973) The Lesch-Nyhan syndrome. Metabolic studies during administration of adenine. Z Kinderheilkd 114: 119–130.PubMedCrossRefGoogle Scholar
  11. Dreifuss FE, Newcombe DS, Shapiro SL, Sheppard GL (1968) X-linked primary hyperuricemia (hypoxanthine-guanine phosphoribosyltransferase deficiency encephalopathy). J Ment Defic Res 12: 100–105.PubMedGoogle Scholar
  12. Emmerson BT, Wyngaarden JB (1969) Purine metabolism in heterozygous carriers of hypoxanthine-guanine phosphoribosyltransferase deficiency. Science 166: 1533–1534.PubMedCrossRefGoogle Scholar
  13. Emmerson BT, Thompson CJ, Wallace DC (1972) Partial deficiency of hypoxanthineguanine phosphoribosyltransferase: Intermediate enzyme deficiency in heterozygote red cells. Ann Intern Med 76: 285–287.PubMedGoogle Scholar
  14. Emmerson BT, Thompson L (1973 a) The spectrum of hypoxanthine-guanine phosphoribosyltransferase deficiency. Q J Med 42: 423–440.PubMedGoogle Scholar
  15. Emmerson BT, Gordon RB, Thompson L (1973 b) Adenine phosphoribosyltransferase deficiency in a female with gout. Isr J Med Sci 9: 1090–1091.Google Scholar
  16. Fujimoto WY, Greene ML, Seegmiller JE (1968) X-linked uric aciduria with neurological disease and self-mutilation: Diagnostic test for the enzyme defect. J Pediatr 73: 920–922.PubMedCrossRefGoogle Scholar
  17. Gibbs DA, McFadyen IR, Crawfurd Md’A, de Muinck Keizer EE, Headhouse-Benson CM, Wilson TM, Farrant PH (1984) First-trimester diagnosis of Lesch-Nyhan syndrome. Lancet II: 1180–1183.CrossRefGoogle Scholar
  18. Gomez GA, Stutzman L, Chu TM (1978) Xanthine nephropathy during chemotherapy in deficiency of hypoxanthine-guanine phosphoribosyltransferase. Arch Intern Med 138: 1017–1019.PubMedCrossRefGoogle Scholar
  19. Greene ML, Fujimoto WY, Seegmiller JE (1969) Urinary xanthine stones — a rare complication of allopurinol therapy. N Engl J Med 280: 426–427.PubMedCrossRefGoogle Scholar
  20. Gröbner W, Zöllner N (1979) Eigenschaften der Hypoxanthinguaninphosphoribosyltransferase bei einem Gichtpatienten mit verminderter Aktivität dieses Enzyms. Klin Wochenschr 57: 63–68.PubMedCrossRefGoogle Scholar
  21. Gröbner W, Ritz E, Zöllner N (1981) Hypoxanthinguaninphosphoribosyltransferase (HGPRTase) aus Erythrozyten bei einem Gichtpatienten mit verminderter Aktivität dieses Enzyms und Niereninsuffizienz. Verh Dtsch Ges Inn Med 87: 1001–1002.Google Scholar
  22. Gutman AB, Yü TF (1957) Renal function in gout. Am J Med 23: 600–622.PubMedCrossRefGoogle Scholar
  23. Henderson JF, Rosenbloom FM, Kelley WN, Seegmiller JE (1968) Variations in purine metabolism of cultured skin fibroblasts from patients with gout. J Clin Invest 47: 1511–1516.PubMedCrossRefGoogle Scholar
  24. Hers H-G, van den Berghe G (1979) Enzyme defect in primary gout. Lancet I: 585–586.CrossRefGoogle Scholar
  25. 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.PubMedCrossRefGoogle Scholar
  26. Holmes EW, Wyngaarden JB, Kelley WN (1973) The regulation of PRPP amidotransferase in man. Clin Res 21: 87 (Abstract)Google Scholar
  27. Hooft C, Van Nevel C, De Schaepdryver AF (1968) Hyperuricosuric encephalopathy without hyperuricaemia. Arch Dis Child 43: 734–737.PubMedCrossRefGoogle Scholar
  28. Jezewska MM (1973) Xanthine accumulation during hypoxanthine oxydation by milk xanthine oxidase. Eur J Biochem 36: 385–390.PubMedCrossRefGoogle Scholar
  29. Kaufman JM, Greene ML, Seegmiller JE (1968) Urine uric acid to creatinine ratio — a screening test for disorders of purine metabolism. J Pediatr 73: 583–592.PubMedCrossRefGoogle Scholar
  30. Kelley WN (1980) Gout and uric acid excretion levels. JAMA 243: 1271–1275.CrossRefGoogle Scholar
  31. Kelley WN, Rosenbloom FM, Henderson JF, Seegmiller JE (1967) A specific enzyme defect in gout associated with overproduction of uric acid. Proc Natl Acad Sci USA 57: 1735–1739.PubMedCrossRefGoogle Scholar
  32. Kelley WN, Greene ML, Rosenbloom FM, Henderson JF, Seegmiller JE (1969) Hypoxanthine-guanine phosphoribosyltransferase deficiency in gout. Ann Intern Med 70: 155–206.PubMedGoogle Scholar
  33. Kelley WN, Wyngaarden JB (1983) Clinical syndromes associated with hypoxanthineguanine phosphoribosyltransferase deficiency. In: Stanbury JB, Wyngaarden JB, Fredrickson DS, Goldstein JL, Brown MS (eds) The metabolic basis of inherited disease, 5th edn McGraw-Hill, New York, pp 1115–1143.Google Scholar
  34. Klinenberg JR, Goldfinger SE, Seegmiller JE (1965) The effectiveness of the xanthine oxidase inhibitor allopurinol in the treatment of gout. Ann Intern Med 62: 639–647.PubMedGoogle Scholar
  35. Lesch M, Nyhan WL (1964) A familial disorder of uric acid metabolism and central nervous system function. Am J Med 36: 561–570.PubMedCrossRefGoogle Scholar
  36. Löffler W, Simmonds HA, Gröbner W (1983 b) Gout and uric acid nephropathy: Some new aspects in diagnosis and treatment. Klin Wochenschr 61: 1233–1239.PubMedCrossRefGoogle Scholar
  37. Löffler W, Gröbner W, Wolfram G, Zöllner N (1983 b) Die endogene Harnsäuresynthese des Menschen. Verh Dtsch Ges Inn Med 89: 678–679.Google Scholar
  38. Löffler W, Gröbner W (1983c) Hypoxanthine phosphoribosyltransferase. In: Bergmeyer H-U (ed) Methods of enzymatic analysis 3rd edn. Bd III Verlag Chemie, Weinheim, pp 399–407.Google Scholar
  39. Löffler W, Wingen A-M, Reiter S, Gröbner W, Zöllner N (1986) Stabilization against haemolysis during haemodialysis of a mutant HPRT. Adv Exp Med Biol 195A: 189–196.Google Scholar
  40. Löffler W, Simmonds HA, Metges C, Gibson T, Zöllner N, Fairbanks LD, Morris GS (1987) Uric acid production and turnover in patients with gout and renal insufficiency of rare origin. Klin Wochenschr 65(Suppl X): 6–7.Google Scholar
  41. Löffler W, Gröbner W (1988 a) Diagnostik von Enzymdefekten des Purinstoffwechsels bei der primären Gicht. Lab Med 12: 311–316.Google Scholar
  42. Löffler W, Gröbner W (1988b) A study of dose-response relationships of allopurinol in the presence of low or high purine turnover. Klin Wochenschr 66: 153–159.PubMedCrossRefGoogle Scholar
  43. Marcolongo R, Marinello E, Pompucci G, Pagani R (1974) The role of xanthine oxidase in hyperuricemic states. Arthritis Rheum 17: 430–438.PubMedCrossRefGoogle Scholar
  44. van Maris, AGCCM, Tax WJM, Oei TL et al. (1980) Phosphoribosylpyrophosphate and enzymes of purine metabolism in erythrocytes from young hyperuricemic males. Biochem Med 23: 263–271.PubMedCrossRefGoogle Scholar
  45. Mayer von Schopf E (1930) Gicht bei einem 5 Wochen alten Säugling. Klin Wochenschr 9: 2148–2151.CrossRefGoogle Scholar
  46. Michener WM (1967) Hyperuricemia and mental retardation with athetosis and selfmutilation. Am J Dis Child 113: 195–206.PubMedGoogle Scholar
  47. 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.PubMedCrossRefGoogle Scholar
  48. Rijksen G, Staal GEJ, van der Vlist MJM et al. (1981) Partial hypoxanthine-guanine phosphoribosyl transferase deficiency with full expression of the Lesch-Nyhan syndrome. Hum Genet 57: 39–47.PubMedCrossRefGoogle Scholar
  49. Rosenberg D, Monnet P, Mamelle JL, Colombel M, Salle B, Bovier-Lapierre M (1968) Encephalopathie avec troubles du métabolisme des purines. Presse Med 76: 2333–2338.Google Scholar
  50. Scherzer AL, Ilson JB (1969) Normal intelligence in the Lesch-Nyhan syndrome. Pediatrics 44: 116–119.PubMedGoogle Scholar
  51. Seegmiller JE, Klinenberg JR, Miller J, Watts RWE (1968) Suppression of glycine-15N incorporation into urinary uric acid by adenine-8-13C in normal and gouty subjects. J Clin Invest 47: 1193–1203.PubMedCrossRefGoogle Scholar
  52. Shin-Buehring YS, Osang M, Wirtz A, Haas B, Rahm P, Schaub J (1980) Prenatal diagnosis of Lesch-Nyhan syndrome and some characteristics of hypoxanthine-guanine phosphoribosyltransferase and adenine phosphoribosyltransferase in human tissues and cultivated cells. Pediatr Res 14: 825–829.PubMedCrossRefGoogle Scholar
  53. Simmonds HA (1986) 2,8-Dihydroxyadenine lithiasis — epidemiology, pathogenesis and therapy. Verh Dtsch Ges Inn Med 92: 503–508.PubMedGoogle Scholar
  54. Simmonds HA, Webster DR, Wilson J, Lingham S (1982) An X-linked syndrome characterised by hyperuricaemia, deafness, and neurodevelopmental abnormalities. Lancet II: 68–70.CrossRefGoogle Scholar
  55. Simmonds HA, Van Acker KJ (1983) Adenine phosphoribosyltransferase deficiency: 2,8-dihydroxyadenine lithiasis. In: Stanbury JB, Wyngaarden JB, Fredrickson DS, Goldstein JL, Brown MS (eds) The metabolic basis of inherited disease, 5th edn. McGraw-Hill, New York, pp 1144–1156.Google Scholar
  56. Simmonds HA, Fairbanks LD, Morris GS, Webster DR, Harley EH (1988) Altered erythrocyte nucleotide patterns are characteristic of inherited disorders of purine or pyrimidine metabolism. Clin Chim Acta 171: 197–210.PubMedCrossRefGoogle Scholar
  57. Sorensen LB (1980) Gout secondary to chronic renal disease: Studies on urate metabolism. Ann Rheum Dis 39: 424–430.PubMedCrossRefGoogle Scholar
  58. Sperling O, Eilam G, Persky-Brosh S, de Vries A (1972) Accelerated erythrocyte 5-phosphoribosyl-1-pyrophosphate synthesis. A familial abnormality associated with excessive uric acid production and gout. Biochem Med 6: 310–316.PubMedCrossRefGoogle Scholar
  59. Sperling O, Brosh S, Boer P, Liberman UA, de Vries A (1978) Urinary xanthine stones in an allopurinol-treated gouty patient with partial deficiency of hypoxanthineguanine phosphoribosyltransferase. Isr J Med Sci 14: 288–292.PubMedGoogle Scholar
  60. Stafford W, Emmerson BT (1984) Effect of purine restriction on serum and urine urate in normal subjects. Adv Exp Med Biol 165A: 309–316.Google Scholar
  61. Talbott JH (1981) ‚It’s gout until proven otherwise‘. Curr Rheumatol 2: 1–7.Google Scholar
  62. Thannhauser SJ (1929) Lehrbuch des Stoffwechsels und der Stoffwechselkrankheiten. Bergmann, München.CrossRefGoogle Scholar
  63. Wingen A-M, Löffler W, Waldherr R, Schärer K (1984) Acute renal failure in an infant with partial deficiency of hypoxanthine-guanine phosphoribosyltransferase. Proc EDTA-ERA 21: 751–756.Google Scholar
  64. Wyngaarden JB (1957) Overproduction of uric acid as the cause of hyperuricemia in primary gout. J Clin Invest 36: 1508–1515.PubMedCrossRefGoogle Scholar
  65. Wyngaarden JB (1974) Metabolic defects of primary hyperuricemia and gout. Am J Med 56: 651–664.PubMedCrossRefGoogle Scholar
  66. Wyngaarden JB (1982) Inherited disorders of purine metabolism. Verh Dtsch Ges Inn Med 88: 1254–1259.Google Scholar
  67. Wyngaarden JB, Kelley WN (1978) Gout. In: Stanbury JB, Wyngaarden JB, Fredrickson DS (eds) The metabolic basis of inherited disease, 4th edn. McGraw-Hill, New York, pp 916–1010.Google Scholar
  68. Wyngaarden JB, Kelley WN (1983) Gout. In: Stanbury JB, Wyngaarden JB, Fredrickson DS, Goldstein JL, Brown MS (eds) The metabolic basis of inherited disease, 5th edn. McGraw-Hill, New York, pp 1043–1114.Google Scholar
  69. van der Zee SPM, Lommen EJP, Trijbels JMF, Schretlen EDAM (1970) The influence of adenine on the clinical features and purine metabolism in the Lesch-Nyhan syndrome. Acta Paediatr Scand 59: 259–264.PubMedCrossRefGoogle Scholar
  70. Zöllner N (1960) Moderne Gichtprobleme. Ätiologie, Pathogenese, Klinik. Ergeb Inn Med Kinderheilk 14: 321–389.Google Scholar
  71. Zoref E, De Vries A, Sperling O (1975) Mutant feedback-resistent phosphoribosylpyrophosphate synthetase associated with purine overproduction and gout. J Clin Invest 56: 1093–1099.PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 1990

Authors and Affiliations

  • W. Löffler
  • W. Gröbner

There are no affiliations available

Personalised recommendations