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Distinguishing primary from secondary Δ 4 ‐3‐oxosteroid 5β‐reductase ( SRD 5B1, AKR 1D1 ) deficiency by urinary steroid analysis
Author(s) -
Yanagi Tadahiro,
Mizuochi Tatsuki,
Homma Keiko,
Ueki Isao,
Seki Yoshitaka,
Hasegawa Tomonobu,
Takei Hajime,
Nittono Hiroshi,
Kurosawa Takao,
Matsuishi Toyojiro,
Kimura Akihiko
Publication year - 2015
Publication title -
clinical endocrinology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.055
H-Index - 147
eISSN - 1365-2265
pISSN - 0300-0664
DOI - 10.1111/cen.12596
Subject(s) - bile acid , medicine , endocrinology , cholestasis , urinary system , reductase , gamma glutamyltransferase , neonatal cholestasis , chemistry , enzyme , biochemistry , biliary atresia , liver transplantation , transplantation
Summary 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 SRD 5B1 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. SRD 5B1 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‐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 T 2 ‐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.