Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2016 Mar;79(3):378-86.
doi: 10.1038/pr.2015.247. Epub 2015 Nov 23.

Inherited disorders of bilirubin clearance

Naureen Memon  1 , Barry I Weinberger  2 , Thomas Hegyi  1 , Lauren M Aleksunes  3
Affiliations
Review

Inherited disorders of bilirubin clearance

Naureen Memon et al. Pediatr Res. 2016 Mar.

Abstract

Inherited disorders of hyperbilirubinemia may be caused by increased bilirubin production or decreased bilirubin clearance. Reduced hepatic bilirubin clearance can be due to defective (i) unconjugated bilirubin uptake and intrahepatic storage, (ii) conjugation of glucuronic acid to bilirubin (e.g., Gilbert syndrome, Crigler-Najjar syndrome, Lucey-Driscoll syndrome, breast milk jaundice), (iii) bilirubin excretion into bile (Dubin-Johnson syndrome), or (iv) conjugated bilirubin re-uptake (Rotor syndrome). In this review, the molecular mechanisms and clinical manifestations of these conditions are described, as well as current approaches to diagnosis and therapy.

PubMed Disclaimer

Conflict of interest statement

Disclosure/Conflict of interest: Authors have no conflict of interest to disclose.

Figures

Figure 1
Figure 1
Schematic view of transporters and enzymes involved in hepatic bilirubin clearance. (Alb, albumin; BCRP, breast cancer resistance protein; BMG, bilirubin monoglucuronide; BDG, bilirubin diglucuronide; GST, glutathione-S-transferase; MRP, multidrug resistance-associated protein; OATP, organic anion transport protein; UCB, unconjugated bilirubin; UGT, uridine diphosphate glucuronosyl transferase).
Figure 2
Figure 2
Schematic representation of the UGT1 gene locus and the UGT1A1 protein. (Chr, chromosome; PR, promoter regions; UGT, uridine diphosphate glucuronosyl transferase).
Figure 3
Figure 3
Schematic view of transporters and enzymes involved in inherited disorders of bilirubin clearance. (Alb, albumin; BCRP, breast cancer resistance protein; BMG, bilirubin monoglucuronide; BDG, bilirubin diglucuronide; CN, Crigler-Najjar; DJS, Dubin-Johnson syndrome; GS, Gilbert syndrome; GST, glutathione-S-transferase; MRP, multidrug resistance-associated protein; OATP, organic anion transport protein; RS, Rotor syndrome; UCB, unconjugated bilirubin; UGT, uridine diphosphate glucuronosyl transferase).
See this image and copyright information in PMC

References

    1. London IM, West R, Shemin D, Rittenberg D. On the origin of bile pigment in normal man. J Biol Chem. 1950;184:351–8. - PubMed
    1. Watchko JF, Tiribelli C. Bilirubin-induced neurologic damage--mechanisms and management approaches. N Engl J Med. 2013;369:2021–30. - PubMed
    1. Sorrentino D, Berk PD. Mechanistic aspects of hepatic bilirubin uptake. Semin Liver Dis. 1988;8:119–36. - PubMed
    1. Hagenbuch B, Meier PJ. Organic anion transporting polypeptides of the OATP/SLC21 family: phylogenetic classification as OATP/SLCO superfamily, new nomenclature and molecular/functional properties. Pflugers Arch. 2004;447:653–65. - PubMed
    1. Briz O, Serrano MA, MacIas RI, Gonzalez-Gallego J, Marin JJ. Role of organic anion-transporting polypeptides, OATP-A, OATP-C and OATP-8, in the human placenta-maternal liver tandem excretory pathway for foetal bilirubin. Biochem J. 2003;371:897–905. - PMC - PubMed

Publication types

MeSH terms

Supplementary concepts