title: Distinguishing primary from secondary Δ(4) -3-oxosteroid 5β-reductase (SRD5B1, AKR1D1) deficiency by urinary steroid analysis.
abstract: OBJECTIVE
  Deficiency of Δ(4) -3-oxosteroid 5β-reductase (5β-reductase), a bile acid synthesis disorder, presents findings of neonatal cholestasis and hyper-3-oxo-Δ(4) bile aciduria. The 5β-reductase enzyme participates in not only bile acid synthesis but also hepatic steroid metabolism. Deficiency of 5β-reductase includes 2 types: primary deficiency, with an SRD5B1 gene mutation; and secondary deficiency, lacking a mutation. Secondary deficiency is caused by fulminant liver failure from various aetiologies including neonatal hemochromatosis (NH). Distinguishing primary from secondary deficiency based on γ-glutamyltransferase (GGT), serum total bile acids (TBA), and urinary bile acid analysis using gas chromatography-mass spectroscopy (GC-MS) is very difficult. SRD5B1 gene analysis is the only reliable method. We examined urinary steroid analysis as a way to distinguish primary from secondary 5β-reductase deficiency.
  
  
  METHODS
  We examined 12 patients with cholestatic jaundice, normal or slightly elevated GGT, and hyper-3-oxo-Δ(4) bile aciduria using urinary steroid analysis by GC-MS of both cortisol and cortisone compounds, such as 5β-tetrahydrocortisol (5β-THF) and 5β-tetrahydrocortisone (5β-THE). Patients previously were diagnosed with primary 5β-reductase deficiency (n = 3), deficiency secondary to NH (n = 3) and deficiency secondary to other liver disorders (n = 6).
  
  
  RESULTS
  Urinary steroid analysis in 3 primary deficiency and 3 NH patients showed low 5β-THE and elevated 5α/5β-THE ratios, making distinction difficult without also considering the clinical course and abdominal magnetic resonance imaging (MRI) findings, such as a very low signal intensity in liver and/or pancreas, especially in T2 -weighted images. In the six patients with other secondary deficiencies, urinary 5β-THF and 5α/5β-THF differed from those in primary deficiency (P < 0·05).
  
  
  CONCLUSIONS
  Urinary steroid analysis can distinguish primary and NH-related deficiencies from other secondary deficiencies.
authors.affiliation: Department of Pediatrics and Child Health, Kurume University School of Medicine, Kurume, Japan.
authors.forename: Tadahiro
authors.initials: T
authors.lastname: Yanagi
authors.forename: Tatsuki
authors.initials: T
authors.lastname: Mizuochi
authors.forename: Keiko
authors.initials: K
authors.lastname: Homma
authors.forename: Isao
authors.initials: I
authors.lastname: Ueki
authors.forename: Yoshitaka
authors.initials: Y
authors.lastname: Seki
authors.forename: Tomonobu
authors.initials: T
authors.lastname: Hasegawa
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: Toyojiro
authors.initials: T
authors.lastname: Matsuishi
authors.forename: Akihiko
authors.initials: A
authors.lastname: Kimura
mesh_terms: D001647:Bile Acids and Salts / Q000097:blood; D005260:Female; D006432:Hemochromatosis / Q000097:blood / Q000201:enzymology; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D007232:Infant, Newborn, Diseases / Q000097:blood / Q000201:enzymology; D041781:Jaundice, Obstructive / Q000097:blood / Q000201:enzymology; D008297:Male; D010088:Oxidoreductases / Q000172:deficiency* / Q000235:genetics; D013256:Steroids / Q000652:urine*; D005723:gamma-Glutamyltransferase / Q000378:metabolism
chemical_list: D001647:Bile Acids and Salts; D013256:Steroids; D010088:Oxidoreductases; C021936:3-oxo-5 beta-steroid delta 4-dehydrogenase; D005723:gamma-Glutamyltransferase