title: Byler disease: early natural history.
abstract: OBJECTIVE
  Byler disease, originally described in Amish kindred, results from mutations in ATPase Class I Type 8b Member 1 (ATP8b1). Specific clinical reports of Amish Byler disease were last published 40 years ago. These investigations were directed at the present detailed clinical understanding of the early course of hepatic manifestations of Byler disease.
  
  
  METHODS
  This study analyzed routine clinical practice and outcomes of children with Byler disease (defined by homozygous c.923G>T mutation in ATP8b1), who initially presented to Children's Hospital of Pittsburgh of UPMC between January 2007 and October 2014. Data were analyzed to the earlier of 24 months of age or partial external biliary diversion.
  
  
  RESULTS
  Six children presented between 1 and 135 days of life: 2 presented with newborn direct hyperbilirubinemia, 2 had complications of coagulopathy, 1 had failure to thrive and rickets, and 1 sibling was identified by newborn genetic testing. Intensive fat-soluble vitamin supplementation was required to prevent insufficiencies in vitamins D, E, and K. Hyperbilirubinemia was variable both over time and between children. Serum bile acid levels were elevated, whereas γ-glutamyltranspeptidase levels were low normal. Scratching behavior (pruritus) was intractable in 4 of 6 children with onset between 6 and 12 months of age. Features of portal hypertension were not observed. Partial external biliary diversion was used during the second year of life in 4 children.
  
  
  CONCLUSIONS
  Detailed analysis of Byler disease revealed varied disease presentation and course. Nutritional issues and pruritus dominated the clinical picture in the first 2 years of life.
authors.affiliation: *Children's Hospital of Pittsburgh of UPMC †University of Pittsburgh School of Medicine, Pittsburgh, PA.
authors.forename: Amy L
authors.initials: AL
authors.lastname: Morris
authors.forename: Kathryn
authors.initials: K
authors.lastname: Bukauskas
authors.forename: Rachel E
authors.initials: RE
authors.lastname: Sada
authors.forename: Benjamin L
authors.initials: BL
authors.lastname: Shneider
mesh_terms: D000251:Adenosine Triphosphatases / Q000235:genetics*; D001361:Avitaminosis / Q000209:etiology; D001647:Bile Acids and Salts / Q000097:blood; D001652:Bile Ducts / Q000473:pathology* / Q000601:surgery; D002780:Cholestasis, Intrahepatic / Q000453:epidemiology / Q000473:pathology* / Q000628:therapy; D005183:Failure to Thrive / Q000453:epidemiology / Q000209:etiology; D005820:Genetic Testing; D006761:Hospitals; D006801:Humans; D006932:Hyperbilirubinemia / Q000453:epidemiology / Q000209:etiology; D015994:Incidence; D007223:Infant; D007231:Infant, Newborn; D008099:Liver / Q000473:pathology*; D009154:Mutation; D010414:Pennsylvania / Q000453:epidemiology; D015995:Prevalence; D011537:Pruritus / Q000209:etiology; D012279:Rickets / Q000453:epidemiology / Q000209:etiology; D005723:gamma-Glutamyltransferase / Q000097:blood
chemical_list: D001647:Bile Acids and Salts; D005723:gamma-Glutamyltransferase; D000251:Adenosine Triphosphatases; C111067:ATP8B1 protein, human