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. 1978 Sep;19(9):838–843. doi: 10.1136/gut.19.9.838

Role of bilirubin overproduction in revealing Gilbert's syndrome: is dyserythropoiesis an important factor?

J M Metreau, J Yvart, D Dhumeaux, P Berthelot
PMCID: PMC1412182  PMID: 101425

Abstract

Gilbert's syndrome was diagnosed in 37 patients with unconjugated hyperbilirubinaemia without overt haemolysis or structural liver abnormality, who had a marked reduction in hepatic bilirubin UDP-glucuronosyltransferase activity (B-GTA) (as compared with that of 23 normal subjects). No significant correlation existed in these patients between serum bilirubin level and the values of B-GTA, thus suggesting that factors other than a low B-GTA must influence the degree of hyperbilirubinaemia in Gilbert's syndrome. Studies of 51Cr erythrocyte survival and 59Fe kinetics in 10 unselected patients demonstrated slight haemolysis in eight, whereas mild ineffective erythropoiesis was suggested in all from a low 24-hour incorporation of radioactive iron into circulating red cells. This overproduction of bilirubin resulting from mild haemolysis and perhaps dyserythropoiesis might reflect only an extreme degree of the normal situation. It certainly contributes to the hyperbilirubinaemia of Gilbert's syndrome and may play a major role in the manifestation of this condition.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. ARIAS I. M. Chronic unconjugated hyperbilirubinemia without overt signs of hemolysis in adolescents and adults. J Clin Invest. 1962 Dec;41:2233–2245. doi: 10.1172/JCI104682. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Arias I. M., Gartner L. M., Cohen M., Ezzer J. B., Levi A. J. Chronic nonhemolytic unconjugated hyperbilirubinemia with glucuronyl transferase deficiency. Clinical, biochemical, pharmacologic and genetic evidence for heterogeneity. Am J Med. 1969 Sep;47(3):395–409. doi: 10.1016/0002-9343(69)90224-1. [DOI] [PubMed] [Google Scholar]
  3. Auclair C., Feldmann G., Hakim J., Boivin P., Boucherot J., Troube Bilirubin and paranitrophenol glucuronyl transferase activities and ultrastructural aspect of the liver in patients with chronic hemolytic anemias. Biomedicine. 1976 Apr 20;25(2):61–65. [PubMed] [Google Scholar]
  4. BILLING B. H., WILLIAMS R., RICHARDS T. G. DEFECTS IN HEPATIC TRANSPORT OF BILIRUBIN IN CONGENITAL HYPERBILIRUBINAEMIA: AN ANALYSIS OF PLASMA BILIRUBIN DISAPPEARANCE CURVES. Clin Sci. 1964 Oct;27:245–257. [PubMed] [Google Scholar]
  5. Berk P. D., Blaschke T. F. Detection of Gilbert's syndrome in patients with hemolysis. A method using radioactive chromium. Ann Intern Med. 1972 Oct;77(4):527–531. doi: 10.7326/0003-4819-77-4-527. [DOI] [PubMed] [Google Scholar]
  6. Berk P. D., Blaschke T. F., Scharschmidt B. F., Waggoner J. G., Berlin N. I. A new approach to quantitation of the various sources of bilrubin in man. J Lab Clin Med. 1976 May;87(5):767–780. [PubMed] [Google Scholar]
  7. Berk P. D., Blaschke T. F., Waggoner J. G. Defective bromosulfophthalein clearance in patients with constitutional hepatic dysfunction (Gilbert's syndrome). Gastroenterology. 1972 Sep;63(3):472–481. [PubMed] [Google Scholar]
  8. Berk P. D., Bloomer J. R., Howe R. B., Berlin N. I. Constitutional hepatic dysfunction (Gilbert's syndrome). A new definition based on kinetic studies with unconjugated radiobilirubin. Am J Med. 1970 Sep;49(3):296–305. doi: 10.1016/s0002-9343(70)80020-1. [DOI] [PubMed] [Google Scholar]
  9. Black M., Billing B. H., Heirwegh K. P. Determination of bilirubin UDP-glucuronyl transferase activity in needle-biopsy specimens of human liver. Clin Chim Acta. 1970 Jul;29(1):27–35. doi: 10.1016/0009-8981(70)90216-0. [DOI] [PubMed] [Google Scholar]
  10. Black M., Billing B. H. Hepatic bilirubin udp-glucuronyl transferase activity in liver disease and gilbert's syndrome. N Engl J Med. 1969 Jun 5;280(23):1266–1271. doi: 10.1056/NEJM196906052802303. [DOI] [PubMed] [Google Scholar]
  11. Black M., Fevery J., Parker D., Jacobson J., Billing B. H., Carson E. R. Effect of phenobarbitone on plasma (14C)bilirubin clearance in patients with unconjugated hyperbilirubinaemia. Clin Sci Mol Med. 1974 Jan;46(1):1–17. doi: 10.1042/cs0460001. [DOI] [PubMed] [Google Scholar]
  12. Black M., Perrett R. D., Carter A. E. Hepatic bilirubin UDP-glucuronyl transferase activity and cytochrome P450 content in a surgical population, and the effects of preoperative drug therapy. J Lab Clin Med. 1973 May;81(5):704–712. [PubMed] [Google Scholar]
  13. Blaschke T. F., Berk P. D., Scharschmidt B. F., Guyther J. R., Vergalla J. M., Waggoner J. G. Crigler-Najjar syndrome: an unusual course with development of neurologic damage at age eighteen. Pediatr Res. 1974 May;8(5):573–590. doi: 10.1203/00006450-197405000-00006. [DOI] [PubMed] [Google Scholar]
  14. Conney A. H. Pharmacological implications of microsomal enzyme induction. Pharmacol Rev. 1967 Sep;19(3):317–366. [PubMed] [Google Scholar]
  15. FAUVERT R. E. The concept of hepatic clearance. Gastroenterology. 1959 Nov;37:603–616. [PubMed] [Google Scholar]
  16. FOULK W. T., BUTT H. R., OWEN C. A., Jr, WHITCOMB F. F., Jr, MASON H. L. Constitutional hepatic dysfunction (Gilbert's disease): its natural history and related syndromes. Medicine (Baltimore) 1959 Feb;38(1):25–46. [PubMed] [Google Scholar]
  17. Faille A., Najean Y., Dresch C. Cinétique de l'érythropoïse dans 14 cas d'érythropoïse inefficace avec anomalies morphologiques des érythroblastes et polynucléarité. Nouv Rev Fr Hematol. 1972 Sep-Oct;12(5):631–651. [PubMed] [Google Scholar]
  18. Felsher B. F., Carpio N. M. Caloric intake and unconjugated hyperbilirubinemia. Gastroenterology. 1975 Jul;69(1):42–47. [PubMed] [Google Scholar]
  19. Felsher B. F., Craig J. R., Carpio N. Hepatic bilirubin glucuronidation in Gilbert's syndrome. J Lab Clin Med. 1973 Jun;81(6):829–837. [PubMed] [Google Scholar]
  20. GRAY S. J., STERLING K. The tagging of red cells and plasma proteins with radioactive chromium. J Clin Invest. 1950 Dec;29(12):1604–1613. doi: 10.1172/JCI102403. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. LOWRY O. H., ROSEBROUGH N. J., FARR A. L., RANDALL R. J. Protein measurement with the Folin phenol reagent. J Biol Chem. 1951 Nov;193(1):265–275. [PubMed] [Google Scholar]
  22. Martin J. F., Vierling J. M., Wolkoff A. W., Scharschmidt B. F., Vergalla J., Waggoner J. G., Berk P. D. Abnormal hepatic transport of indocyanine green in Gilbert's syndrome. Gastroenterology. 1976 Mar;70(3):385–391. [PubMed] [Google Scholar]
  23. NAJEAN Y., ARDAILLOU N., DRESCH C., TUBIANA M. TECHNIQUE D''ETUDE DE L''ERYTHROPOUI'ESE 'A L'AIDE DU FER RADIO-ACTIF. Rev Fr Etud Clin Biol. 1965 Mar;10:321–329. [PubMed] [Google Scholar]
  24. Powell L. W., Billing B. H., Williams H. S. An assessment of red cell survival in idiopathic unconjugated hyperbilirubinaemia (Gilbert's syndrome) by the use of radioactive diisopropylfluorophosphate and chromium. Australas Ann Med. 1967 Aug;16(3):221–225. doi: 10.1111/imj.1967.16.3.221. [DOI] [PubMed] [Google Scholar]
  25. Powell L. W., Hemingway E., Billing B. H., Sherlock S. Idiopathic unconjugated hyperbilirubinemia (Gilbert's syndrome). A study of 42 families. N Engl J Med. 1967 Nov 23;277(21):1108–1112. doi: 10.1056/NEJM196711232772102. [DOI] [PubMed] [Google Scholar]
  26. SCHMID R., HAMMAKER L. Glucuronide formation in patients with constitutional hepatic dysfunction (Gilbert's disease). N Engl J Med. 1959 Jun 25;260(26):1310–1314. doi: 10.1056/NEJM195906252602603. [DOI] [PubMed] [Google Scholar]
  27. Verwilghen R. L., Lewis S. M., Dacie J. V., Crookston J. H., Crookston M. C. Hempas: congenital dyserythropoietic anaemia (type II). Q J Med. 1973 Apr;42(166):257–278. [PubMed] [Google Scholar]

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