title: Characterization of urinary bile acids in a pediatric BRIC-1 patient: effect of rifampicin treatment.
abstract: BACKGROUND
  Benign recurrent intrahepatic cholestasis type 1 (BRIC-1), a rare autosomal recessive disorder characterized by recurrent episodes of jaundice and pruritus, is caused by mutations in the ATP8B1 gene. Rifampicin has been reported to be an effective treatment of jaundice and pruritus in patients with BRIC. Proposed mechanisms of effect for rifampicin include enhancement of multidrug-resistance protein 2 expression, activation of the enzymes of uridine diphosphate glucuronosyltransferase 1A1 and cytochrome P450 3A4, and stimulation of 6α-hydroxylation of bile acids.
  
  
  METHODS
  To confirm the diagnosis of BRIC-1 and demonstrate the effect of rifampicin treatment on bile acid metabolism, we analyzed the patient's ATP8B1 gene and bile acids in urine.
  
  
  RESULTS
  We detected 2 heterozygous mutations in the ATP8B1 gene, and increasing amounts of unusual bile acids such as 1β-hydroxylated cholic acid, 2β-hydroxylated cholic acid, 4β-hydroxylated cholic acid, 6α-hydroxylated cholic acid, and hyocholic acid in urine during rifampicin treatment.
  
  
  CONCLUSIONS
  We diagnosed a jaundiced pediatric patient with BRIC-1 caused by 2 novel mutations (1226delA/2210delA) in the ATP8B1 gene. Rifampicin was effective in treating cholestasis. Results of urinary bile acid analyses during rifampicin treatment in this patient, suggested that rifampicin might stimulate 1β-, 2β-, and 4β-hydroxylation of bile acids in addition to 6α-hydroxylation.
authors.affiliation: Department of Pediatrics and Child Health, Kurume University School of Medicine, Kurume, Japan. mizuochi_tatsuki@kurume-u.ac.jp
authors.forename: Tatsuki
authors.initials: T
authors.lastname: Mizuochi
authors.forename: Akihiko
authors.initials: A
authors.lastname: Kimura
authors.forename: Atsushi
authors.initials: A
authors.lastname: Tanaka
authors.forename: Akina
authors.initials: A
authors.lastname: Muto
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Nittono
authors.forename: Yoshitaka
authors.initials: Y
authors.lastname: Seki
authors.forename: Tomoyuki
authors.initials: T
authors.lastname: Takahashi
authors.forename: Takao
authors.initials: T
authors.lastname: Kurosawa
authors.forename: Masayoshi
authors.initials: M
authors.lastname: Kage
authors.forename: Hajime
authors.initials: H
authors.lastname: Takikawa
authors.forename: Toyojiro
authors.initials: T
authors.lastname: Matsuishi
mesh_terms: D000251:Adenosine Triphosphatases / Q000235:genetics*; D001647:Bile Acids and Salts; D002648:Child; D002779:Cholestasis / Q000188:drug therapy / Q000235:genetics; D002780:Cholestasis, Intrahepatic / Q000188:drug therapy* / Q000235:genetics / Q000652:urine*; D019826:Cholic Acid / Q000378:metabolism / Q000652:urine; D002793:Cholic Acids / Q000378:metabolism / Q000652:urine; D005260:Female; D006801:Humans; D006900:Hydroxylation; D009154:Mutation; D012293:Rifampin / Q000494:pharmacology / Q000627:therapeutic use*
chemical_list: D001647:Bile Acids and Salts; D002793:Cholic Acids; C004821:muricholic acid; D000251:Adenosine Triphosphatases; C111067:ATP8B1 protein, human; D019826:Cholic Acid; D012293:Rifampin