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- Title
Distinguishing primary from secondary Δ<sup>4</sup>-3-oxosteroid 5β-reductase ( SRD5B1, AKR1D1) deficiency by urinary steroid analysis.
- Authors
Yanagi, Tadahiro; Mizuochi, Tatsuki; Homma, Keiko; Ueki, Isao; Seki, Yoshitaka; Hasegawa, Tomonobu; Takei, Hajime; Nittono, Hiroshi; Kurosawa, Takao; Matsuishi, Toyojiro; Kimura, Akihiko
- Abstract
Objective Deficiency of Δ4-3-oxosteroid 5β-reductase (5β-reductase), a bile acid synthesis disorder, presents findings of neonatal cholestasis and hyper-3-oxo-Δ4 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. Design, patients and measurements We examined 12 patients with cholestatic jaundice, normal or slightly elevated GGT, and hyper-3-oxo-Δ4 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.
- Subjects
DEFICIENCY diseases; CHOLESTASIS in newborn infant; STEROID drugs; BILE acids; HEMOCHROMATOSIS; REDUCTASE inhibitors
- Publication
Clinical Endocrinology, 2015, Vol 82, Issue 3, p346
- ISSN
0300-0664
- Publication type
Article
- DOI
10.1111/cen.12596