In:
Clinical Endocrinology, Wiley, Vol. 82, No. 3 ( 2015-03), p. 346-351
Abstract:
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.
Type of Medium:
Online Resource
ISSN:
0300-0664
,
1365-2265
DOI:
10.1111/cen.2015.82.issue-3
Language:
English
Publisher:
Wiley
Publication Date:
2015
detail.hit.zdb_id:
2004597-9
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