Manifestations of Inherited Disorders of Bilirubin Glucuronidation During Infancy and Childhood

  • Namita Roy Chowdhury
  • Yaron Ilan
  • Jayanta Roy Chowdhury
Part of the Current Clinical Practice book series (CCP)


Biliary excretion of bilirubin requires its conversion to glucuronides by the hepatic microsomal enzyme bilirubin-UDP-glucuronosyltransferase (bilirubin-UGT) (1). Three grades of inherited deficiency of bilirubin-UGT have been described. A near-absence of bilirubin-UGT activity results in the most severe of these disorders, Crigler-Najjar syndrome type I. Severe, but incomplete, deficiency of the transferase activity leads to Crigler-Najjar syndrome type II, also known as Arias syndrome. A mild reduction of bilirubin-UGT activity is the most common, and produces the innocuous Gilbert’ s syndrome, in which a low level of hyperbilirubinemia is the only significant clinical feature (2).


Serum Bilirubin Level Neonatal Jaundice Neonatal Hyperbilirubinemia Serum Bilirubin Concentration Unconjugated Hyperbilirubinemia 
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.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Roy Chowdhury J, Jansen PLM. Metabolism of bilirubin. In: Zakim D, Boyer TD, eds. Hepatology: a textbook of liver disease, 3rd ed. Saunders, Philadelphia, 1996, pp. 323–347.Google Scholar
  2. 2.
    Roy Chowdhury J, Roy Chowdhury N, Arias IM. Hereditary jaundice and disorders of bilirubin metabolism. In: Sciver, Boudet, Sly, Valle, eds. The metabolic and molecular bases of inherited disease, 7th ed. McGraw Hill, New York, 1995, pp. 2161–2208.Google Scholar
  3. 3.
    Crigler JF, Najjar VA. Congenital familial non-hemolytic jaundice with kernicterus. Pediatrics 1952; 10:169.PubMedGoogle Scholar
  4. 4.
    Wolkoff AW, Roy Chowdhury J, et al. Crigler-Najjar syndrome (Type I) in an adult male. Gastroenterology 1979;76:840–848.PubMedGoogle Scholar
  5. 5.
    Arias IM, Gartner LM, Cohen M, Benezzer J, Levi AJ. Chronic nonhemolytic unconjugated hyperbilirubine-mia with glucuronyltransferase deficiency: Clinical, biochemical, pharmacologic, and genetic evidence for heterogeneity. Am J Med 1969;47:395.PubMedCrossRefGoogle Scholar
  6. 6.
    Gollan JL, Huang SM, Billing B, Sherlock S. Prolonged survival in three brothers with severe type II Crigler-Najjar syndrome. Ultrastructural and metabolic studies. Gastroenterology 1975;68:1543.PubMedGoogle Scholar
  7. 7.
    Roy Chowdhury J, Roy Chowdhury N. Unveiling the mysteries of inherited disorders of bilirubin glucuronidation. Gastroenterology 1993;105:288–293.Google Scholar
  8. 8.
    Bosma PJ, Roy Chowdhury N, Goldhoorn BG, et al. Sequence of exons and the flanking regions of human bilirubin-UDPglucuronosyltransferase gene complex and identification of a genetic mutation in a patient with Crigler-Najjar syndrome, Type I. Hepatology 1992; 15:941–947.PubMedCrossRefGoogle Scholar
  9. 9.
    Huang TJ, Lahiri P, Oude Elferink RPJ, et al. Mechanism of inherited deficiencies of multiple UDP-glucuronosyltransferase isoforms in two patients with Crigler-Najjar syndrome, Type I. FASEB J 1992;6:2859.PubMedGoogle Scholar
  10. 10.
    Ritter JK, Yeatman MT, Ferriera P, Owens IS. Identification of a genetic alteration in the code for bilirubin UDP-glucuronosyltransferase in the UGT1 gene complex of a Crigler-Najjar syndrome, Type I. J Clin Invest 1992;90:150.PubMedCrossRefGoogle Scholar
  11. 11.
    Roy Chowdhury J, Roy Chowdhury N, Wu G, Shouval R, Arias IM. Bilirubin monoglucuronide and diglucuronide formation by human liver in vitro: assay by high pressure liquid chromatography. Hepatology 1981;1:622.CrossRefGoogle Scholar
  12. 12.
    Sengupta KS, Gantla VR, Bommineni P, et al. Prenatal identification of Crigler-Najjar syndrome type 1 genotype by analysis of chronic villus sample DNA. Hepatology 1994;13:320A.Google Scholar
  13. 13.
    Gilbert A, Lereboullet P. La cholemie simple familiale. Semin Med 1991;21:241.Google Scholar
  14. 14.
    Powell LW, Hemingway E, Billing BH, Sherlock S. Idiopathic unconjugated hyperbilirubinemia (Gilbert’s syndrome): a study of 42 families. N Engl J Med 1967;277:1108.PubMedCrossRefGoogle Scholar
  15. 15.
    Bosma PJ, Roy Chowdhury J, Bakker C, et al. A sequence abnormality in the promoter region results in reduced expression of bilirubin-UDP-glucuronosyltransferase-1 in Gilbert syndrome. N Engl J Med 1995;333:1171–1179.PubMedCrossRefGoogle Scholar
  16. 16.
    Mollison PL, Cutbush M. Hemolytic disease of the newborn: criterial of severity. Brit Med J 1949; 1:123.PubMedCrossRefGoogle Scholar
  17. 17.
    Schenker S, Hoyumpa AM, McCandless DW. Bilirubin toxicity to the brain (kernicterus) and other tissues. In: Ostrow JD, ed. Bile pigments and jaundice. Marcel Dekker, New York, 1986, pp. 395–419.Google Scholar
  18. 18.
    Turkel SB, Miller CA, Guttenberg ME, Moynes DR, Hodgman JE. A clinical pathologic reappraisal of kernicterus. Pediatrics 1982;69:267.PubMedGoogle Scholar
  19. 19.
    Cornford EM, Braun LD, Oldendorp WH, Hill CA. Comparison of lipid-mediated blood brain barrier penetrability in neonates and adults. Am J Physiol 1982;243:C161.PubMedGoogle Scholar
  20. 20.
    Laas R, Helmke K. Regional cerebral blood flow following unilateral blood-brain barrier alteration induced by hyperosmolar perfusion in the albino rat. In: Cervos-Navarro J, Fritschka E, eds. erebral circulation and metabolism. Raven, New York, 1981, pp. 317–321.Google Scholar
  21. 21.
    Engle WD, Avant BS Jr. Neonatal hyperbilirubinemia and renal function. J Pediatr 1982; 100:113–116.PubMedCrossRefGoogle Scholar
  22. 22.
    Berk PD, Martin F, Blaschkle TF, Scharschmidt BF, Plotz PH. Unconjugated hyperbilirubinemia: physiological evaluation and experimental approaches to therapy. Ann Intern Med 1975;82:552.PubMedGoogle Scholar
  23. 23.
    Kaufman SS, Wood RP, Shaw BW, et al. Orthotopic liver transplantation for type I Crigler-Najjar syndrome. Hepatology 1986;6:1259.PubMedCrossRefGoogle Scholar
  24. 24.
    Galbraith RA, Drummond GS, Kappas A. Suppression of bilirubin production in the Crigler-Najjar, Type I syndrome: studies with heme oxygenase inhibitor-tin-mesopor. Pediatrics 1992;89:175.PubMedGoogle Scholar
  25. 25.
    Kapitulnick J. The role of cytochrome P-450 in the alternate pathways of bilirubin metabolism in congenitally jaundiced Gun rats and infants with the Crigler-Najjar syndrome, Type I. Int Bilirubin Workshop, Trieste, 1992, p. 53.Google Scholar
  26. 26.
    Demetriou AA, Levenson SM, Whiting J, et al. Replacement of hepatic functions in rats by transplantation of microcarrier-attached hepatocytes. Science 1986;233:1190.PubMedCrossRefGoogle Scholar
  27. 27.
    Takahashi M, Ilan Y, Sengupta K, Roy Chowdhury N, Roy Chowdhury J. Induction of tolerance to recombinant adenoviruses by injection into newborn rats: long term amelioration of hyperbilirubinemia in Gunn rats. J Biol Chem 1996;271:26,536.Google Scholar
  28. 28.
    Ilan Y, Attavar P, Takahashi M, et al. Induction of central tolerance by intrathymic inoculation of adenoviral antigens into the host thymus permits long-term gene therapy in Gunn rats. J Clin Invest 1996;98:2640.PubMedCrossRefGoogle Scholar

Suggested Reading

  1. 1.
    Suchy FJ, Shneider BL. Neonatal jaundice and cholestasis in liver and biliary diseases. Williams and Wilkins, Philadelphia, 1996, pp. 495–510.Google Scholar
  2. 2.
    Schenker S, Hoyumpa AM, McCandless DW. Bilirubin toxicity to the brain (kernicterus) and other tissues. In: Ostrow JD, ed. Bile pigments and jaundice. Marcel Dekker, New York, 1986, pp. 395–419.Google Scholar

Copyright information

© Springer Science+Business Media New York 1998

Authors and Affiliations

  • Namita Roy Chowdhury
  • Yaron Ilan
  • Jayanta Roy Chowdhury

There are no affiliations available

Personalised recommendations