Volume 82, Issue 3 pp. 346-351

Original Article

Distinguishing primary from secondary Δ⁴-3-oxosteroid 5β-reductase (SRD5B1, AKR1D1) deficiency by urinary steroid analysis

Tadahiro Yanagi,

Tadahiro Yanagi

Department of Pediatrics and Child Health, Kurume University School of Medicine, Kurume, Japan

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Tatsuki Mizuochi,

Tatsuki Mizuochi

Department of Pediatrics and Child Health, Kurume University School of Medicine, Kurume, Japan

Division of Gastroenterology, Hepatology and Nutrition, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA

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Keiko Homma,

Keiko Homma

Central Clinical Laboratories, Keio University Hospital, Tokyo, Japan

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Isao Ueki,

Isao Ueki

Department of Pediatrics and Child Health, Kurume University School of Medicine, Kurume, Japan

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Yoshitaka Seki,

Yoshitaka Seki

Department of Pediatrics and Child Health, Kurume University School of Medicine, Kurume, Japan

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Tomonobu Hasegawa,

Tomonobu Hasegawa

Department of Pediatrics, Keio University School of Medicine, Tokyo, Japan

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Hajime Takei,

Hajime Takei

Institution of Bile Acid, Junshin Clinic, Tokyo, Japan

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Hiroshi Nittono,

Hiroshi Nittono

Institution of Bile Acid, Junshin Clinic, Tokyo, Japan

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Takao Kurosawa,

Takao Kurosawa

Faculty of Pharmaceutical Sciences, Health Sciences University of Hokkaido, Hokkaido, Japan

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Toyojiro Matsuishi,

Toyojiro Matsuishi

Department of Pediatrics and Child Health, Kurume University School of Medicine, Kurume, Japan

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Akihiko Kimura,

Corresponding Author

Akihiko Kimura

Department of Pediatrics and Child Health, Kurume University School of Medicine, Kurume, Japan

Correspondence: Akihiko Kimura, Department of Pediatrics and Child Health, Kurume University School of Medicine, 67 Asahi-machi, Kurume-shi 830-0011, Japan. Tel.: 81-942-31-7565; Fax: 81-942-38-1792; E-mail: [email protected]Search for more papers by this author

Tadahiro Yanagi,

Tadahiro Yanagi

Department of Pediatrics and Child Health, Kurume University School of Medicine, Kurume, Japan

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Tatsuki Mizuochi,

Tatsuki Mizuochi

Department of Pediatrics and Child Health, Kurume University School of Medicine, Kurume, Japan

Division of Gastroenterology, Hepatology and Nutrition, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA

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Keiko Homma,

Keiko Homma

Central Clinical Laboratories, Keio University Hospital, Tokyo, Japan

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Isao Ueki,

Isao Ueki

Department of Pediatrics and Child Health, Kurume University School of Medicine, Kurume, Japan

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Yoshitaka Seki,

Yoshitaka Seki

Department of Pediatrics and Child Health, Kurume University School of Medicine, Kurume, Japan

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Tomonobu Hasegawa,

Tomonobu Hasegawa

Department of Pediatrics, Keio University School of Medicine, Tokyo, Japan

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Hajime Takei,

Hajime Takei

Institution of Bile Acid, Junshin Clinic, Tokyo, Japan

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Hiroshi Nittono,

Hiroshi Nittono

Institution of Bile Acid, Junshin Clinic, Tokyo, Japan

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Takao Kurosawa,

Takao Kurosawa

Faculty of Pharmaceutical Sciences, Health Sciences University of Hokkaido, Hokkaido, Japan

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Toyojiro Matsuishi,

Toyojiro Matsuishi

Department of Pediatrics and Child Health, Kurume University School of Medicine, Kurume, Japan

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Akihiko Kimura,

Corresponding Author

Akihiko Kimura

Department of Pediatrics and Child Health, Kurume University School of Medicine, Kurume, Japan

First published: 22 August 2014

https://doi.org/10.1111/cen.12596

Citations: 4

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Summary

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.

Supporting Information

References

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Citing Literature

Volume82, Issue3

March 2015

Pages 346-351

Filename	Description
cen12596-sup-0001-TableS1.docWord document, 34 KB	Table S1. Clinical data of patients with acute and chronic liver failure (patients No. 7-12).
cen12596-sup-0002-FigS1.pptapplication/mspowerpoint, 164 KB	Figure S1. Genomic DNA analysis in patient 1.

Distinguishing primary from secondary Δ⁴-3-oxosteroid 5β-reductase (SRD5B1, AKR1D1) deficiency by urinary steroid analysis

Summary

Objective

Design, patients and measurements

Results

Conclusions

Supporting Information

References

Citing Literature

References

Information

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Distinguishing primary from secondary Δ4-3-oxosteroid 5β-reductase (SRD5B1, AKR1D1) deficiency by urinary steroid analysis

Summary

Objective

Design, patients and measurements

Results

Conclusions

Supporting Information

References

Citing Literature

References

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Distinguishing primary from secondary Δ⁴-3-oxosteroid 5β-reductase (SRD5B1, AKR1D1) deficiency by urinary steroid analysis