Inherited disorders of bilirubin transport and conjugation: new insights into molecular mechanisms and consequences

Gastroenterology. 2014 Jun;146(7):1625-38. doi: 10.1053/j.gastro.2014.03.047. Epub 2014 Apr 1.


Inherited disorders of bilirubin metabolism might reduce bilirubin uptake by hepatocytes, bilirubin conjugation, or secretion of bilirubin into bile. Reductions in uptake could increase levels of unconjugated or conjugated bilirubin (Rotor syndrome). Defects in bilirubin conjugation could increase levels of unconjugated bilirubin; the effects can be benign and frequent (Gilbert syndrome) or rare but severe, increasing the risk of bilirubin encephalopathy (Crigler-Najjar syndrome). Impairment of bilirubin secretion leads to accumulation of conjugated bilirubin (Dubin-Johnson syndrome). We review the genetic causes and pathophysiology of disorders of bilirubin transport and conjugation as well as clinical and therapeutic aspects. We also discuss the possible mechanisms by which hyperbilirubinemia protects against cardiovascular disease and the metabolic syndrome and the effects of specific genetic variants on drug metabolism and cancer development.

Keywords: Bile Secretion; Crigler–Najjar Syndrome; Glucuronosyl Transferase; Hepatic Storage Disease; Kernicterus.

Publication types

  • Review

MeSH terms

  • Animals
  • Bile / metabolism
  • Bile Acids and Salts / metabolism*
  • Biological Transport
  • Crigler-Najjar Syndrome / genetics
  • Crigler-Najjar Syndrome / metabolism
  • Genetic Predisposition to Disease
  • Gilbert Disease / genetics
  • Gilbert Disease / metabolism
  • Hepatocytes / metabolism
  • Heredity
  • Humans
  • Hyperbilirubinemia, Hereditary / genetics
  • Hyperbilirubinemia, Hereditary / metabolism*
  • Hyperbilirubinemia, Hereditary / physiopathology
  • Jaundice, Chronic Idiopathic / genetics
  • Jaundice, Chronic Idiopathic / metabolism
  • Liver / metabolism*
  • Membrane Transport Proteins / genetics
  • Membrane Transport Proteins / metabolism*
  • Pedigree
  • Phenotype


  • Bile Acids and Salts
  • Membrane Transport Proteins