Hyperbilirubinemia syndromes (Gilbert-Meulengracht, Crigler-Najjar, Dubin-Johnson, and Rotor syndrome)

Best Pract Res Clin Gastroenterol. 2010 Oct;24(5):555-71. doi: 10.1016/j.bpg.2010.07.007.


Hyperbilirubinemia is an important clinical sign that often indicates severe hepatobiliary disease of different etiologies. Inherited non-haemolytichyperbilirubinemic conditions include Dubin-Johnson, Rotor, and Gilbert-Meulengracht syndromes, which are important differential diagnoses indicating benign disease that require no immediate treatment. Dubin-Johnson and Rotor syndromes are rare, exhibit mixed direct and indirect hyperbilirubinemia as well as typical profiles or urinary coproporphyrin excretion. Gilbert-Meulengracht disease leads to unconjugated hyperbilirubinemia because of impaired glucuronidation activity, and is part of a spectrum of genetic variants also encompassing fatal Crigler-Najjar syndrome. Gilbert-Meulengracht syndrome can be diagnosed by clinical presentation, biochemistry and genotyping, and carries significance regarding the disposition towards drug-associated toxicity. In addition, the precise diagnosis of these inherited hyperbilirubinemic syndromes avoids unnecessary invasive procedures for suspected more severe hepatobiliary disease.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Antineoplastic Agents, Phytogenic / therapeutic use
  • Bilirubin / metabolism
  • Camptothecin / analogs & derivatives
  • Camptothecin / therapeutic use
  • Crigler-Najjar Syndrome / diagnosis
  • Crigler-Najjar Syndrome / genetics
  • Diagnosis, Differential
  • Genetic Predisposition to Disease / epidemiology
  • Genetic Variation
  • Gilbert Disease / diagnosis
  • Gilbert Disease / drug therapy
  • Gilbert Disease / genetics
  • Glucuronosyltransferase / genetics*
  • Humans
  • Hyperbilirubinemia, Hereditary / diagnosis
  • Hyperbilirubinemia, Hereditary / genetics*
  • Hyperbilirubinemia, Hereditary / metabolism
  • Irinotecan
  • Jaundice, Chronic Idiopathic / diagnosis
  • Jaundice, Chronic Idiopathic / genetics
  • Neoplasms / physiopathology


  • Antineoplastic Agents, Phytogenic
  • Irinotecan
  • Glucuronosyltransferase
  • Bilirubin
  • Camptothecin