Familial cholestasis: progressive familial intrahepatic cholestasis, benign recurrent intrahepatic cholestasis and intrahepatic cholestasis of pregnancy.
Progressive familial intrahepatic cholestasis (PFIC) type 1, 2 and 3 are due to mutations in ATP8B1, ABCB11 and ABCB4, respectively. Each of these genes encodes a hepatocanalicular transporter, which is essential for the proper formation of bile. Mutations in ABCB4 can result in progressive cholestatic disease, while mutations in ATP8B1 and ABCB11 can result both in episodic cholestasis, referred to as benign recurrent intrahepatic cholestasis (BRIC) type 1 and 2, as well as in progressive cholestatic disease. This suggests a clinical continuum and these diseases are therefore preferably referred to as ATP8B1 deficiency and ABCB11 deficiency. Similarly PFIC type 3 is designated as ABCB4 deficiency. Heterozygous mutations in each of these transporters can also be associated with intrahepatic cholestasis of pregnancy. This review summarizes the pathophysiology, clinical features and current as well as future therapeutic options for progressive familial- and benign recurrent intrahepatic cholestasis as well as intrahepatic cholestasis of pregnancy.
Department of Paediatric Gastroenterology (KE.01.144.3), Wilhelmina Children's Hospital, University Medical Centre Utrecht, Post-Box 85090, 3508 AB Utrecht, The Netherlands. wwoerd@umcutrecht.nl
Wendy L
WL
van der Woerd
Saskia W C
SW
van Mil
Janneke M
JM
Stapelbroek
Leo W J
LW
Klomp
Stan F J
SF
van de Graaf
Roderick H J
RH
Houwen
D018435:ATP Binding Cassette Transporter, Subfamily B / Q000235:genetics*; D000074020:ATP Binding Cassette Transporter, Subfamily B, Member 11; D018528:ATP-Binding Cassette Transporters / Q000235:genetics*; D000251:Adenosine Triphosphatases / Q000235:genetics*; D001647:Bile Acids and Salts / Q000032:analysis; D002780:Cholestasis, Intrahepatic / Q000145:classification / Q000175:diagnosis / Q000209:etiology / Q000235:genetics* / Q000503:physiopathology / Q000628:therapy; D018450:Disease Progression; D005260:Female; D006801:Humans; D009154:Mutation; D011247:Pregnancy; D011248:Pregnancy Complications / Q000209:etiology / Q000235:genetics / Q000628:therapy; D012008:Recurrence; D014580:Ursodeoxycholic Acid / Q000627:therapeutic use
C093491:ABCB11 protein, human; D018435:ATP Binding Cassette Transporter, Subfamily B; D000074020:ATP Binding Cassette Transporter, Subfamily B, Member 11; D018528:ATP-Binding Cassette Transporters; D001647:Bile Acids and Salts; D014580:Ursodeoxycholic Acid; C095122:multidrug resistance protein 3; D000251:Adenosine Triphosphatases; C111067:ATP8B1 protein, human