Gilbert's disease

Last reviewed 01/2018

Gilbert's disease is a benign, mildly symptomatic, non- haemolytic, unconjugated hyperbilirubinaemia in the absence of liver disease (1).

• it is a common cause of isolated raised unconjugated bilirubin (2)
• total plasma bilirubin can be as high as 80 mumol/l and mild intermittent jaundice does occur
• inheritance pattern is probably autosomal recessive (3)
• has been estimated that some 10-15% of the Western population suffers from Gilbert's syndrome

The main abnormality is decreased bilirubin conjugating capacity (4)

• bilirubin-uridinediphosphate-glucuronosyltransferase (UGT1A1) is the only enzyme involved in the conjugation of bilirubin
• in patients with Gilbert's syndrome, hepatic glucuronidation by UGT1A1 is reduced to about 30% of normal (1)
• although Gilbert’s syndrome does not lead to progressive liver damage it has attracted attention regarding the pharmacogenetics of drug metabolism
  • apart from being the only physiological UGT capable of bilirubin glucuronidation, UGT1A1 also catalyzes the glucuronidation of 2-hydroxy-estrone and estradiol, and a number of therapeutic drugs such as ethinylestradiol, gemfibrozil, metabolites of irinotecan, simvastatin and buprenorphine

Reference:

• (1) Farheen S et al. Gilbert's syndrome: High frequency of the (TA)7 TAA allele in India and its interaction with a novel CAT insertion in promoter of the gene for bilirubin UDP-glucuronosyltransferase 1 gene. World J Gastroenterol. 2006;12(14):2269-75
• (2) Smellie WS, Ryder SD. Biochemical "liver function tests". BMJ. 2006;333(7566):481-3
• (3) Ned Tijdschr Geneeskd. 2002 Aug 10;146(32):1488-90
• (4) Kaplan M. Genetic interactions in the pathogenesis of neonatal hyperbilirubinemia: Gilbert's Syndrome and glucose-6-phosphate dehydrogenase deficiency. J Perinatol. 2001;21 Suppl 1:S30-4
• (5) Editorial. Gilbert's syndrome - a legitimate genetic anomaly? NEJM 1995;333 (18): 1217-8.
• (6)Pediatr Int. 2002 Aug;44(4):427-32