Primary ∆4-3-oxosteroid 5β-reductase deficiency: Two cases in China
Open accessAbstract
Aldo-keto reductase 1D1 (AKR1D1) deficiency, a rare but life-threatening form of bile acid deficiency, has not been previously described in China. Here, we describe the first two primary ∆4-3-oxosteroid 5β-reductase deficiency patients in Mainland China diagnosed by fast atom bombardment-mass spectroscopy of urinary bile acids and confirmed by genetic analysis. A high proportion of atypical 3-oxo-∆4-bile acids in the urine indicated a deficiency in ∆4-3-oxosteroid 5β-reductase. All of the coding exons and adjacent intronic sequence of the AKR1D1 gene were sequenced using peripheral lymphocyte genomic DNA of two patients and one of the patient's parents. One patient exhibited compound heterozygous mutations: c.396C>A and c.722A>T, while the other was heterozygous for the mutation c.797G>A. Based on these mutations, a diagnosis of primary ∆4-3-oxosteroid 5β-reductase deficiency could be confirmed. With ursodeoxycholic acid treatment and fat-soluble vitamin supplements, liver function tests normalized rapidly, and the degree of hepatomegaly was markedly reduced in both patients.
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Seven point mutations are known in patients with 5β-reductase deficiency: Leu106Phe, Pro133Arg, Gly223Glu, Pro198Leu, Asp241Val, Arg261Cys, and Arg266Glu.
“seven point mutations have been identified in patients with 5β-reductase deficiency: Leu106Phe, Pro133Arg, Gly223Glu, Pro198Leu, Asp241Val, Arg261Cys and Arg266Glu [95–97, 99, 100].”
From Role of aldo-keto reductase family 1 (AKR1) enzymes in human steroid metabolism (2014) · cites this paper as [100]
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Setchell, K. D. R., Suchy, F. J., Welsh, M. B., Zimmer-Nechemias, L., Heubi, J. E., & Balistreri, W. F. (1988) · Journal of Clinical Investigation · doi:10.1172/jci113837 · Cited by 254 · see citing works
Mechanisms of disease: inborn errors of bile acid synthesis
Sundaram, S. S., Bove, K. E., Lovell, M. A., & Sokol, R. J. (2008) · Nature Clinical Practice Gastroenterology & Hepatology · doi:10.1038/ncpgasthep1179 · Cited by 146 · see citing works
Defects in Bile Acid Biosynthesis‐Diagnosis and Treatment
Setchell, K. D. R., & Heubi, J. E. (2006) · Journal of Pediatric Gastroenterology and Nutrition · doi:10.1097/01.mpg.0000226386.79483.7b · Cited by 137 · see citing works
Gonzales, E. M., Gerhardt, M. F., Fabrè, M., Setchell, K. D. R., Spraul, A., Vincent, I., Heubi, J. E., Bernard, O., & Jacquemin, E. (2009) · Gastroenterology · doi:10.1053/j.gastro.2009.07.043 · Cited by 126 · see citing works
Lemonde, H. A., Custard, E. J., Bouquet, J., Duran, M., Overmars, H., Scambler, P. J., & Clayton, P. T. (2003) · Gut · doi:10.1136/gut.52.10.1494 · Cited by 125 · see citing works
Disorders of Bile Acid Synthesis
Clayton, P. T. (2011) · Springer eBooks · doi:10.1007/978-3-642-15720-2_34 · Cited by 11 · see citing works
Flagged first, then by citations
Research works printed but not linked: 3
- Drury JE, Mindnich R, Penning TM. Characterization of disease-related 5beta-reductase (AKR1D1) mutations reveals their potential to cause bile acid deficiency. J Biol Chem 2010; 285: 24529-24537
- Ueki I, Kimura A, Chen HL, Yorifuji T, Mori J, Itoh S, Maruyama K, Ishige T, Takei H, Nittono H, Kurosawa T, Kage M, Matsuishi T. SRD5B1 gene analysis needed for the accurate diagnosis of primary 3-oxo-Delta4-steroid 5beta- reductase deficiency. J Gastroenterol Hepatol 2009; 24: 776-785
- Sumazaki R, Nakamura N, Shoda J, Kurosawa T, Tohma M. Gene analysis in delta 4-3-oxosteroid 5 beta-reductase defi- ciency. Lancet 1997; 349: 329
Cited by
Sorted by citations
Role of aldo-keto reductase family 1 (AKR1) enzymes in human steroid metabolism
Rižner, T. L., & Penning, T. M. (2014) · Steroids · doi:10.1016/j.steroids.2013.10.012 · Cited by 217 · see citing works
Disorders of bile acid synthesis
Clayton, P. T. (2011) · Journal of Inherited Metabolic Disease · doi:10.1007/s10545-010-9259-3 · Cited by 170 · see citing works
5β-Reduced steroids and human Δ4-3-ketosteroid 5β-reductase (AKR1D1)
Chen, M., & Penning, T. M. (2014) · Steroids · doi:10.1016/j.steroids.2014.01.013 · Cited by 55 · see citing works
Nikolaou, N., Hodson, L., & Tomlinson, J. (2021) · The Journal of Steroid Biochemistry and Molecular Biology · doi:10.1016/j.jsbmb.2021.105808 · Cited by 24 · see citing works
Δ4-3-oxosteroid-5β-reductase deficiency: Responses to oral bile acid therapy and long-term outcomes
Zhang, M., Setchell, K. D. R., Zhao, J., Gong, J., Lu, Y., & Wang, J. (2019) · World Journal of Gastroenterology · doi:10.3748/wjg.v25.i7.859 · Cited by 21 · see citing works
Self-citationBile Acid Synthesis Disorders in Japan: Long-Term Outcome and Chenodeoxycholic Acid Treatment
Kimura, A., Mizuochi, T., Takei, H., Ohtake, A., Mori, J., Shinoda, K., Hashimoto, T., Kasahara, M., Togawa, T., Murai, T., et al. (2021) · Digestive Diseases and Sciences · doi:10.1007/s10620-020-06722-4 · Cited by 19 · see citing works
Wang, H. H., Wen, F., Dai, D., Wang, J., Zhao, J., Setchell, K. D. R., Shi, L.-N., Zhou, S., Liu, S., & Yang, Q. (2018) · World Journal of Gastroenterology · doi:10.3748/wjg.v24.i35.4086 · Cited by 18 · see citing works
Self-citationMolecular findings in children with inherited intrahepatic cholestasis
Wang, N., Lu, Y., Gong, J., Xie, X., Lin, J., Abuduxikuer, K., Zhang, M., & Wang, J. (2019) · Pediatric Research · doi:10.1038/s41390-019-0548-8 · Cited by 16 · see citing works
Chen, M., Jin, Y., & Penning, T. M. (2015) · Biochemistry · doi:10.1021/acs.biochem.5b00816 · Cited by 12 · see citing works
∆4-3-oxo-5β-reductase deficiency: favorable outcome in 16 patients treated with cholic acid
Gardin, A., Ruiz, M., Beime, J., Cananzi, M., Rathert, M., Rohmer, B., Grabhorn, E. F., Almes, M., Logarajah, V., Quintana, L. P., et al. (2023) · Orphanet Journal of Rare Diseases · doi:10.1186/s13023-023-02984-z · Cited by 11 · see citing works
Bile acid synthetic defects: Simplified approach in a nutshell
Ravindranath, A., Sarma, M. S., & Yachha, S. K. (2019) · Hepatobiliary & pancreatic diseases international · doi:10.1016/j.hbpd.2019.09.003 · Cited by 7 · see citing works
Disorders of Bile Acid Synthesis
Clayton, P. T. (2016) · Springer eBooks · doi:10.1007/978-3-662-49771-5_33 · Cited by 5 · see citing works
Recurrent AKR1D1 c.580-13T>A Variant
Zhao, J., Qiu, Y., Wang, L., Li, Z., Xie, X., Lu, Y., Setchell, K. D. R., Cheng, Y., Xing, Q.-H., & Wang, J. (2023) · Journal of Molecular Diagnostics · doi:10.1016/j.jmoldx.2023.01.004 · Cited by 4 · see citing works
Self-citationThe Aldo-Keto Reductase Superfamily
Penning, T. M. (2016) · Elsevier eBooks · doi:10.1016/b978-0-12-801238-3.64092-8 · Cited by 4 · see citing works
Disorders of Bile Acid Synthesis
Clayton, P. T. (2022) · Springer eBooks · doi:10.1007/978-3-662-63123-2_38 · Cited by 3 · see citing works
Hepatocellular and Intrahepatic Cholestasis
Knisely, A. S. (2014) · Springer eBooks · doi:10.1007/978-3-642-54053-0_11 · Cited by 2 · see citing works
Cheng, Y., Li, G., Deng, M., & Song, Y. (2017) · PubMed Central · doi:10.7499/j.issn.1008-8830.2017.07.002 · Cited by 2 · see citing works
Primary bile acid synthesis disorders
Васильевна, В. Г., Хавкин, А. И., Потапов, А. С., Андреевна, С. Т., Nikitin, A. V., & Gevorkyan, A. K. (2025) · Russian Journal of Evidence-Based Gastroenterology · doi:10.17116/dokgastro20251401171 · Cited by 1 · see citing works
The Aldo-Keto Reductase Superfamily
Penning, T. M. (2024) · Elsevier eBooks · doi:10.1016/b978-0-323-95488-4.00010-3
El-Koofy, N. M., Elgebaly, H. F., & Elmonem, M. A. (2025) · Egyptian Pediatric Association Gazette · doi:10.1186/s43054-025-00386-3
Hudson, J., Hyunh, S., Rakić, B., & Boerkoel, C. F. (2025) · American Journal of Medical Genetics Part A · doi:10.1002/ajmga.70025
Gardin, A., Ruiz, M., Beime, J., Cananzi, M., Rathert, M., Rohmer, B., Grabhorn, E. F., Almes, M., Logarajah, V., Peña-Quintana, L., et al. (2023) · Figshare · doi:10.6084/m9.figshare.24770249
- Authors
- Zhao, J.
- Affiliations
- Fudan University (CN)
- Corresponding author
- Zhao, Jing
- ORCID
- Zhao, Jing
- Venue
- World Journal of Gastroenterology
- Publisher
- Baishideng Publishing Group Inc.
- Published
- 2012
- Volume
- 18
- Issue
- 47
- Pages
- 7113
- ISSN
- 1007-9327 (ISSN-L)
- PMC
- PMC3531703
- OpenAlex
- W2003501217
- Cited by
- 22
- References
- 6
- Citations by year
- 2025: 3 · 2024: 1 · 2023: 3 · 2022: 1 · 2021: 2 · 2019: 3 · 2018: 1 · 2017: 1 · 2016: 2 · 2015: 1 · 2014: 2 · 2013: 1
- FWCI
- 0.82
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- cc-by-nc
- Locations
- World Journal of Gastroenterology (publishedVersion, cc-by-nc)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Clinical Biochemistry › Metabolism and Genetic Disorders
- Health Sciences › Medicine › Surgery › Pediatric Hepatobiliary Diseases and Treatments
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Sexual Differentiation and Disorders
- Keywords
- bile acid deficiency, urinary bile acids, fast atom bombardment mass spectrometry, compound heterozygosity, hepatomegaly
- MeSH terms
- Bile Acids and Salts, China, DNA Mutational Analysis, Exons, Hepatomegaly, Heterozygote, Humans, Infant, Liver, Male, Mutation, Oxidoreductases, Ursodeoxycholic Acid
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