title: Two neonatal cholestasis patients with mutations in the SRD5B1 (AKR1D1) gene: diagnosis and bile acid profiles during chenodeoxycholic acid treatment.
abstract: OBJECTIVE
  In two Japanese infants with neonatal cholestasis, 3-oxo-Δ(4)-steroid 5β-reductase deficiency was diagnosed based on mutations of the SRD5B1 gene. Unusual bile acids such as elevated 3-oxo-Δ(4) bile acids were detected in their serum and urine by gas chromatography-mass spectrometry. We studied effects of oral chenodeoxycholic acid treatment.
  
  
  METHODS
  SRD5B1 gene analysis used peripheral lymphocyte genomic DNA. Diagnosis and treatment of these two patients were investigated retrospectively and prospectively investigated.
  
  
  RESULTS
  With respect to SRD5B1, one patient was heterozygous (R266Q, a novel mutation) while the other was a compound heterozygote (G223E/R261C). Chenodeoxycholic acid treatment was effective in improving liver function and decreasing unusual bile acids such as 7α-hydroxy- and 7α,12α-dihydroxy-3-oxo-4-cholen-24-oic acids in serum and urine.
  
  
  CONCLUSIONS
  Primary bile acid treatment using chenodeoxycholic acid was effective for these patients treated in early infancy before the late stage of chronic cholestatic liver dysfunction.
authors.affiliation: Department of Pediatrics and Child Health, Kurume University School of Medicine, 67 Asahi-machi, Kurume-shi, Japan.
authors.forename: Yoshitaka
authors.initials: Y
authors.lastname: Seki
authors.forename: Tatsuki
authors.initials: T
authors.lastname: Mizuochi
authors.forename: Akihiko
authors.initials: A
authors.lastname: Kimura
authors.forename: Tomoyuki
authors.initials: T
authors.lastname: Takahashi
authors.forename: Akira
authors.initials: A
authors.lastname: Ohtake
authors.forename: Shin-Ichi
authors.initials: S
authors.lastname: Hayashi
authors.forename: Toshiya
authors.initials: T
authors.lastname: Morimura
authors.forename: Yasuharu
authors.initials: Y
authors.lastname: Ohno
authors.forename: Takayuki
authors.initials: T
authors.lastname: Hoshina
authors.forename: Kenji
authors.initials: K
authors.lastname: Ihara
authors.forename: Hajime
authors.initials: H
authors.lastname: Takei
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Nittono
authors.forename: Takao
authors.initials: T
authors.lastname: Kurosawa
authors.forename: Keiko
authors.initials: K
authors.lastname: Homma
authors.forename: Tomonobu
authors.initials: T
authors.lastname: Hasegawa
authors.forename: Toyojiro
authors.initials: T
authors.lastname: Matsuishi
mesh_terms: D044466:Asian People; D001647:Bile Acids and Salts / Q000378:metabolism*; D002635:Chenodeoxycholic Acid / Q000627:therapeutic use*; D002779:Cholestasis / Q000175:diagnosis* / Q000188:drug therapy* / Q000235:genetics* / Q000378:metabolism; D005260:Female; D005765:Gastrointestinal Agents / Q000627:therapeutic use; D006801:Humans; D007231:Infant, Newborn; D007232:Infant, Newborn, Diseases / Q000175:diagnosis / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism; D008099:Liver / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008297:Male; D009154:Mutation / Q000502:physiology; D010088:Oxidoreductases / Q000235:genetics*
chemical_list: D001647:Bile Acids and Salts; D005765:Gastrointestinal Agents; D002635:Chenodeoxycholic Acid; D010088:Oxidoreductases; C021936:3-oxo-5 beta-steroid delta 4-dehydrogenase