Progressive familial intrahepatic cholestasis.
Progressive familial intrahepatic cholestasis (PFIC), also known as Byler disease, is an inherited disorder of childhood in which cholestasis of hepatocellular origin often presents in the neonatal period and leads to death from liver failure before adolescence. The pattern of appearance of affected children within families is consistent with autosomal recessive inheritance. Several studies have provided support for the heterogeneity of this clinical entity suggesting the existence of different types due to different disorders affecting the hepatocyte and related to defects of bile acid secretion or bile acid metabolism. Recent molecular and genetic studies have identified genes responsible for three types of PFIC and have shown that PFIC was related to mutations in hepatocellular transport system genes involved in bile formation. These findings now provide specific diagnostic tools for the investigation of children with PFIC and should allow prenatal diagnosis in the future. Genotype-phenotype correlations performed in patients treated with ursodeoxycholic acid or biliary diversion should allow those PFIC patients who could benefit from these therapies to be precisely identified. In the future, other therapies, such as cell and gene therapies, might be considered and could also represent an alternative to liver transplantation.
Jacquemin
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Department of Pediatrics and INSERM U 347, Bicêtre Hospital, Le Kremlin Bicêtre, France. emj@kb.inserm.fr
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; D000293:Adolescent; D002675:Child, Preschool; D002756:Cholagogues and Choleretics / Q000627:therapeutic use; D002780:Cholestasis, Intrahepatic / Q000175:diagnosis* / Q000201:enzymology / Q000235:genetics* / Q000628:therapy; D018450:Disease Progression; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D016031:Liver Transplantation; D014580:Ursodeoxycholic Acid / Q000627:therapeutic use; D005723:gamma-Glutamyltransferase / Q000097:blood
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; D002756:Cholagogues and Choleretics; D014580:Ursodeoxycholic Acid; C095122:multidrug resistance protein 3; D005723:gamma-Glutamyltransferase; D000251:Adenosine Triphosphatases; C111067:ATP8B1 protein, human