Abstract
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).
This is a preview of subscription content, log in via an institution.
Buying options
Tax calculation will be finalised at checkout
Purchases are for personal use only
Learn about institutional subscriptionsPreview
Unable to display preview. Download preview PDF.
References
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.
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.
Crigler JF, Najjar VA. Congenital familial non-hemolytic jaundice with kernicterus. Pediatrics 1952; 10:169.
Wolkoff AW, Roy Chowdhury J, et al. Crigler-Najjar syndrome (Type I) in an adult male. Gastroenterology 1979;76:840–848.
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.
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.
Roy Chowdhury J, Roy Chowdhury N. Unveiling the mysteries of inherited disorders of bilirubin glucuronidation. Gastroenterology 1993;105:288–293.
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.
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.
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.
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.
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.
Gilbert A, Lereboullet P. La cholemie simple familiale. Semin Med 1991;21:241.
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.
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.
Mollison PL, Cutbush M. Hemolytic disease of the newborn: criterial of severity. Brit Med J 1949; 1:123.
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.
Turkel SB, Miller CA, Guttenberg ME, Moynes DR, Hodgman JE. A clinical pathologic reappraisal of kernicterus. Pediatrics 1982;69:267.
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.
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.
Engle WD, Avant BS Jr. Neonatal hyperbilirubinemia and renal function. J Pediatr 1982; 100:113–116.
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.
Kaufman SS, Wood RP, Shaw BW, et al. Orthotopic liver transplantation for type I Crigler-Najjar syndrome. Hepatology 1986;6:1259.
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.
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.
Demetriou AA, Levenson SM, Whiting J, et al. Replacement of hepatic functions in rats by transplantation of microcarrier-attached hepatocytes. Science 1986;233:1190.
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.
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.
Suggested Reading
Suchy FJ, Shneider BL. Neonatal jaundice and cholestasis in liver and biliary diseases. Williams and Wilkins, Philadelphia, 1996, pp. 495–510.
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.
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 1998 Springer Science+Business Media New York
About this chapter
Cite this chapter
Chowdhury, N.R., Ilan, Y., Chowdhury, J.R. (1998). Manifestations of Inherited Disorders of Bilirubin Glucuronidation During Infancy and Childhood. In: Wu, G.Y., Israel, J. (eds) Diseases of the Liver and Bile Ducts. Current Clinical Practice. Humana Press, Totowa, NJ. https://doi.org/10.1007/978-1-4612-1808-1_23
Download citation
DOI: https://doi.org/10.1007/978-1-4612-1808-1_23
Publisher Name: Humana Press, Totowa, NJ
Print ISBN: 978-1-4612-7293-9
Online ISBN: 978-1-4612-1808-1
eBook Packages: Springer Book Archive