title: Progressive familial intrahepatic cholestasis: genetic disorders of biliary transporters.
abstract: Progressive familial intrahepatic cholestasis types 1, 2 and 3 are childhood diseases of the liver. Benign recurrent intrahepatic cholestasis is predominantly an adult form with similar clinical symptoms that spontaneously resolve. These genetic disorders have significantly helped to unravel the basic mechanisms of the canalicular bile transport processes. Progressive familial intrahepatic cholestasis type 1 involves a gene also linked to benign recurrent intrahepatic cholestasis. The gene codes for an aminophospholipid translocase protein that maintains the integrity of the membrane. How a mutation in this protein causes cholestasis is unknown but is thought to involve the enterohepatic recirculation of bile acids. Progressive familial intrahepatic cholestasis types 2 and 3 involve the canalicular bile salt export pump and a phospholipid translocase, respectively, both of which are fundamental to bile secretion. This review covers the clinical manifestations, genetics, treatment and mechanism of each disease.
authors.affiliation: ANZAC Research Institute, University of Sydney and Center for Education and Research on Aging, Concord Repatriation General Hospital, Sydney, NSW, Australia.
authors.forename: Matthew J
authors.initials: MJ
authors.lastname: Harris
authors.forename: David G
authors.initials: DG
authors.lastname: Le Couteur
authors.forename: Irwin M
authors.initials: IM
authors.lastname: Arias
mesh_terms: D018528:ATP-Binding Cassette Transporters / Q000378:metabolism*; D000251:Adenosine Triphosphatases / Q000235:genetics*; D001646:Bile / Q000378:metabolism*; D002780:Cholestasis, Intrahepatic / Q000235:genetics* / Q000378:metabolism; D020022:Genetic Predisposition to Disease; D006801:Humans; D009154:Mutation; D012008:Recurrence
chemical_list: D018528:ATP-Binding Cassette Transporters; D000251:Adenosine Triphosphatases; C111067:ATP8B1 protein, human