title: Cholestatic liver disease in adults may be due to an inherited defect in bile acid biosynthesis.
abstract: BACKGROUND
  An increasing number of treatable inborn errors of bile acid synthesis have been described, primarily in infants with severe cholestatic liver disease.
  
  
  RESULTS
  The present patient, whose two older siblings had died from progressive cholestatic liver disease, developed neonatal cholestasis and rickets but recovered during the childhood years and follow-up was terminated at 12 years of age. The patient presented again at 26 years of age with jaundice and pathological liver function tests. This was normalized upon treatment with ursodeoxycholic acid. Electrospray mass spectrometry of urine showed predominance of unsaturated bile acids, characteristic of 3beta-hydroxy-Delta5-C27-steroid dehydrogenase/isomerase (HSD3B7) deficiency. The activity of HSD3B7 in cultured fibroblasts was less than 5% of normal. A single homozygous mutation was found in exon 4 leading to an amino acid exchange (S162R) and loss of enzyme activity.
  
  
  CONCLUSIONS
  This case illustrates that infants with an inherited absence of HSD3B7 may survive the neonatal period of life and childhood without treatment with bile acids. A low level of sulphation of the abnormal trihydroxy bile acid formed as a result of enzyme deficiency may be of importance for survival. The possibility that liver disease presenting in the adult may be due to a mutation in the HSD3B7 gene should be considered, especially in cases with familial occurrence of liver disease and earlier periods of liver dysfunction.
authors.affiliation: Department of Pediatrics, Karolinska University Hospital, Huddinge, Sweden. bjorn.fischler@karolinska.se
authors.forename: B
authors.initials: B
authors.lastname: Fischler
authors.forename: K
authors.initials: K
authors.lastname: Bodin
authors.forename: H
authors.initials: H
authors.lastname: Stjernman
authors.forename: M
authors.initials: M
authors.lastname: Olin
authors.forename: M
authors.initials: M
authors.lastname: Hansson
authors.forename: J
authors.initials: J
authors.lastname: Sjövall
authors.forename: I
authors.initials: I
authors.lastname: Björkhem
mesh_terms: D015096:3-Hydroxysteroid Dehydrogenases / Q000172:deficiency* / Q000235:genetics; D000328:Adult; D001647:Bile Acids and Salts / Q000096:biosynthesis* / Q000097:blood / Q000652:urine; D002478:Cells, Cultured; D002780:Cholestasis, Intrahepatic / Q000235:genetics* / Q000378:metabolism; D005192:Family Health; D005347:Fibroblasts / Q000378:metabolism; D006801:Humans; D008297:Male; D008661:Metabolism, Inborn Errors / Q000235:genetics* / Q000378:metabolism; D009154:Mutation; D017422:Sequence Analysis, DNA / Q000379:methods
chemical_list: D001647:Bile Acids and Salts; D015096:3-Hydroxysteroid Dehydrogenases