title: Proliferation to paucity: evolution of bile duct abnormalities in a case of Alagille syndrome.
abstract: Alagille syndrome is an autosomal dominant disorder characterized by abnormalities in multiple organ systems, including the liver, and is caused by mutations in JAG1. Chronic cholestasis secondary to paucity of interlobular bile ducts is traditionally both a clinical and a pathologic hallmark of this disease at diagnosis. We describe the biliary changes on serial liver biopsies in a patient who presented with jaundice and extrahepatic stigmata of Alagille syndrome. Her initial specimens at 6 and 10 months of age demonstrated interlobular bile duct proliferation and cholestasis, suggestive of distal biliary obstruction. A specimen at 2 years of age showed near-total absence of interlobular bile ducts, with the classic histologic appearance of bile duct paucity. We present this case to underscore the potential pitfalls in interpreting cholestatic liver morphology in the absence of clinical information. The progression of bile duct abnormalities is discussed in the context of the role postulated for JAG1 in postnatal liver growth and development.
authors.affiliation: Department of Pathology, The Children's Hospital and the University of Colorado School of Medicine, 1056 East 19th Avenue, Denver, CO 80218, USA.
authors.forename: G H
authors.initials: GH
authors.lastname: Deutsch
authors.forename: R J
authors.initials: RJ
authors.lastname: Sokol
authors.forename: T H
authors.initials: TH
authors.lastname: Stathos
authors.forename: A S
authors.initials: AS
authors.lastname: Knisely
mesh_terms: D016738:Alagille Syndrome / Q000150:complications / Q000473:pathology*; D001653:Bile Ducts, Intrahepatic / Q000002:abnormalities* / Q000000981:diagnostic imaging; D001706:Biopsy; D002135:Calcium-Binding Proteins; D002455:Cell Division; D002779:Cholestasis / Q000209:etiology / Q000473:pathology; D005260:Female; D006801:Humans; D007223:Infant; D036341:Intercellular Signaling Peptides and Proteins; D000072100:Jagged-1 Protein; D008099:Liver / Q000254:growth & development / Q000378:metabolism; D008565:Membrane Proteins; D011506:Proteins / Q000235:genetics / Q000378:metabolism; D011859:Radiography; D000072099:Serrate-Jagged Proteins
chemical_list: D002135:Calcium-Binding Proteins; D036341:Intercellular Signaling Peptides and Proteins; C000606273:JAG1 protein, human; D000072100:Jagged-1 Protein; D008565:Membrane Proteins; D011506:Proteins; D000072099:Serrate-Jagged Proteins