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.

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 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: Tadahiro Yanagi, Tatsuki Mizuochi, Keiko Homma, Isao Ueki, Yoshitaka Seki, Tomonobu Hasegawa, Hajime Takei, Hiroshi Nittono, Takao Kurosawa, Toyojiro Matsuishi, Akihiko Kimura
• Journal: Clinical endocrinology (Clin Endocrinol (Oxf)) Vol. 82 Issue 3 Pg. 346-51 (Mar 2015) ISSN: 1365-2265 [Electronic] England
• PMID: 25154774 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2014 John Wiley & Sons Ltd.

Chemical References

• Bile Acids and Salts
• Steroids
• Oxidoreductases
• 3-oxo-5 beta-steroid delta 4-dehydrogenase
• gamma-Glutamyltransferase

Topics

• Bile Acids and Salts (blood)
• Female
• Hemochromatosis (blood, enzymology)
• Humans
• Infant
• Infant, Newborn
• Infant, Newborn, Diseases (blood, enzymology)
• Jaundice, Obstructive (blood, enzymology)
• Male
• Oxidoreductases (deficiency, genetics)
• Steroids (urine)
• gamma-Glutamyltransferase (metabolism)