[Childhood cholestasis and bile transporters].
Identification of the transport systems involved in bile secretion and of the genes codifying these systems has allowed the etiology of familial intrahepatic cholestasis to be determined in most affected children. Mutations in ATP8B1 cause a defect in FIC1, an aminophospholipid flipase, and give rise to a variable spectrum of disease, ranging from progressive intrahepatic cholestasis to benign recurrent cholestasis, due to alterations in the lipid composition of the membranes and decreased expression of the nuclear factor FXR. Mutations in ABCB11 cause a defect of the canalicular bile salt export pump (BSEP), with early clinical manifestations and progression to hepatocellular failure in childhood. Mutations in ABCB4 cause an alteration in the MDR3 phospholipid transporter, and a variable spectrum of disease from progressive ductal injury to cirrhosis in children, and gallstones, cholestasis of pregnancy, or late cirrhosis in adults.
Hierro
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L
Servicio de Hepatología y Trasplante, Hospital Infantil Universitario La Paz, Madrid, España. pjara.hulp@salud.madrid.org
Jara
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P
D018435:ATP Binding Cassette Transporter, Subfamily B / Q000172:deficiency / Q000235:genetics; D000074020:ATP Binding Cassette Transporter, Subfamily B, Member 11; D018528:ATP-Binding Cassette Transporters / Q000235:genetics; D000251:Adenosine Triphosphatases / Q000172:deficiency / Q000235:genetics; D000328:Adult; D001647:Bile Acids and Salts / Q000378:metabolism*; D002648:Child; D002675:Child, Preschool; D002780:Cholestasis, Intrahepatic / Q000235:genetics* / Q000378:metabolism; D018450:Disease Progression; D005260:Female; D020022:Genetic Predisposition to Disease; D022781:Hepatocytes / Q000378:metabolism; D006801:Humans; D007223:Infant; D009154:Mutation; D010641:Phenotype; D011247:Pregnancy; D011248:Pregnancy Complications / Q000378:metabolism
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; C095122:multidrug resistance protein 3; D000251:Adenosine Triphosphatases; C111067:ATP8B1 protein, human