Congenital adrenal hyperplasia due to P450 oxidoreductase deficiency
Open accessAbstract
Objective: To raise awareness of Cytochrome P450 Oxidoreductase Deficiency (PORD, a rare form of congenital adrenal hyperplasia (CAH), through a case of pregnant woman with virilization symptoms. Case description: A 30-year-old Chinese woman was referred to hospital after 7 years of presenting signs of virilization, including voice deepening, acromegaly, hirsutism, clitoromegaly, and acne. These symptoms appeared since her third gestation. Her second birth died 9 hours after birth and had signs of clitoris hypertrophy. Her third born was a son who presented with flat nose, radius and humerus bone malformation, and small penis at birth. Panel of POR-related genetic tests revealed that the patient carried c.1370 G>A (p.R457H), which is a POR heterozygous gene, while her husband carried a POR heterozygous gene as well, c.1379 C>A (p.S460Y). Two heterozygous mutations of the POR were found in her son: c.1370 G>A and c.1379 C>A. In PORD, c.1370 G>A (p.R457H) was reported as a susceptible gene, while c.1379 C>A (p.S460Y) has not been reported as responsible for the disease so far. Discussion and literature review: PORD is a rare form of CAH and caused by POR gene mutations. Most PORD patients are identified and diagnosed in pediatrics department. Internal medicine and obstetrics physicians are unfamiliar with the disease. As clinical manifestations are diverse, PORD could be easy to miss or to be misdiagnosed. Typical clinical manifestation includes adrenal insufficiency-related symptoms, such as bone malformations and sexual development disorders. PORD is diagnosed through genetic testing. Investigations of steroid metabolic products in urine through gas chromatography-mass spectrometry or liquid chromatography-mass spectrometry are also helpful for the diagnosis, but neither of them are widely available in China. In this case, the patient had a history of infertility, and her third child was born with congenital defect and carried a PORD-related gene. In general clinical practice, if a pregnant woman presents with abnormal virilization symptoms, CAH possibilities should be considered, including rare causes such as PORD. Conclusion: PORD is a rare autosomal recessive genetic disease. We summarised the clinical characteristics and genotypes that were previously reported in the Chinese population and identified a novel mutation.
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PORD is an ultra-rare autosomal recessive disorder caused by mutations in the POR gene and characterized by highly heterogeneous skeletal, genital, and endocrine manifestations.
“Cytochrome P450 oxidoreductase deficiency (PORD) is an ultra-rare autosomal recessive disorder caused by mutations in the POR gene and characterized by highly heterogeneous skeletal, genital, and endocrine manifestations.”
From Case Report: Integrating clinical presentation and genetic analysis in P450 oxidoreductase deficiency: a novel mutation and systematic review (2026) · cites this paper as [2]
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Cites
Richards, S., Aziz, N., Bale, S., Bick, D., Das, S., Gastier-Foster, J., Grody, W. W., Hegde, M., Lyon, E., Spector, E., et al. (2015) · Genetics in Medicine · doi:10.1038/gim.2015.30 · Cited by 32,594 · see citing works
Arlt, W., Walker, E. A., Draper, N., Ivison, H. E., Ride, J. P., Hammer, F., Chalder, S. M., Borucka-Mankiewicz, M., Hauffa, B. P., Malunowicz, E. M., et al. (2004) · The Lancet · doi:10.1016/s0140-6736(04)16503-3 · Cited by 345 · see citing works
Huang, N., Pandey, A. V., Agrawal, V., Reardon, W., Lapunzina, P. D., Mowat, D., Jabs, E. W., Vliet, G. V., Sack, J., Flück, C. E., et al. (2005) · The American Journal of Human Genetics · doi:10.1086/429417 · Cited by 336 · see citing works
Fukami, M., Horikawa, R., Nagai, T., Tanaka, T., Naiki, Y., Sato, N., Okuyama, T., Nakai, H., Soneda, S., Tachibana, K., et al. (2005) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2004-0810 · Cited by 155 · see citing works
Homma, K., Hasegawa, T., Nagai, T., Adachi, M., Horikawa, R., Fujiwara, I., Tajima, T., Takeda, R., Fukami, M., & Ogata, T. (2006) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2005-2460 · Cited by 153 · see citing works
Peterson, R. E., Imperato-McGinley, J., Gautier, T., & Shackleton, C. (1985) · New England Journal of Medicine · doi:10.1056/nejm198511073131903 · Cited by 148 · see citing works
Overlapping spectra of SMAD4 mutations in juvenile polyposis (JP) and JP–HHT syndrome
Gallione, C. J., Aylsworth, A. S., Beis, J., Berk, T., Bernhardt, B. A., Clark, R. D., Clericuzio, C. L., Danesino, C., Drautz, J. M., Fahl, J., et al. (2010) · American Journal of Medical Genetics Part A · doi:10.1002/ajmg.a.33206 · Cited by 147 · see citing works
Fukami, M., Nishimura, G., Homma, K., Nagai, T., Hanaki, K., Uematsu, A., Ishii, T., Numakura, C., Sawada, H., Nakacho, M., et al. (2009) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2008-2816 · Cited by 117 · see citing works
Fukami, M., Homma, K., Hasegawa, T., & Ogata, T. (2013) · Developmental Dynamics · doi:10.1002/dvdy.23892 · Cited by 114 · see citing works
Biochemical diagnosis of Antley–Bixler syndrome by steroid analysis
Shackleton, C. H. L., Marcos, J., Małunowicz, E., Szarras‐Czapnik, M., Jira, P. E., Taylor, N., Murphy, N., Crushell, E., Gottschalk, M. E., Hauffa, B. P., et al. (2004) · American Journal of Medical Genetics Part A · doi:10.1002/ajmg.a.30104 · Cited by 86 · see citing works
Fukami, M., Hasegawa, T., Horikawa, R., Ohashi, T., Nishimura, G., Homma, K., & Ogata, T. (2006) · Pediatric Research · doi:10.1203/01.pdr.0000195825.31504.28 · Cited by 79 · see citing works
Cragun, D. L., Trumpy, S. K., Shackleton, C. H. L., Kelley, R. I., Leslie, N. D., Mulrooney, N. P., & Hopkin, R. J. (2004) · American Journal of Medical Genetics Part A · doi:10.1002/ajmg.a.30170 · Cited by 37 · see citing works
POR R457H is a global founder mutation causing Antley–Bixler syndrome with autosomal recessive trait
Adachi, M., Asakura, Y., Matsuo, M., Yamamoto, T., Hanaki, K., & Arlt, W. (2006) · American Journal of Medical Genetics Part A · doi:10.1002/ajmg.a.31112 · Cited by 34 · see citing works
Fan, L., Ren, X., Song, Y., Su, C., Fu, J., & Gong, C. (2019) · Orphanet Journal of Rare Diseases · doi:10.1186/s13023-019-1283-2 · Cited by 22 · see citing works
Koyama, Y., Homma, K., Fukami, M., Miwa, M., Ikeda, K., Ogata, T., Murata, M., & Hasegawa, T. (2016) · Clinical Pediatric Endocrinology · doi:10.1297/cpe.25.37 · Cited by 13 · see citing works
Unal, E., Demiral, M., Yıldırım, R., Taş, F. F., Ceylaner, S., & Özbek, M. N. (2021) · Hormones · doi:10.1007/s42000-020-00249-z · Cited by 12 · see citing works
Clinical characteristics of cytochrome P450 oxidoreductase deficiency: a nationwide survey in Japan
Yatsuga, S., Amano, N., Nakamura-Utsunomiya, A., Kobayashi, H., Takasawa, K., Nagasaki, K., Nakamura, A., Nishigaki, S., Numakura, C., Fujiwara, I., et al. (2020) · Endocrine Journal · doi:10.1507/endocrj.ej20-0011 · Cited by 9 · see citing works
Jin, Y., Chen, M., Penning, T. M., & Miller, W. L. (2015) · Biochemical Journal · doi:10.1042/bj20141410 · Cited by 6 · see citing works
[A case of Antley-Bixler syndrome caused by novel POR mutations].
Peng, C., Huang, C., Tan, H., & Wu, L. (2019) · PubMed · doi:10.3760/cma.j.issn.1003-9406.2019.10.019 · Cited by 4 · see citing works
Approach to the patient with cytochrome P450 oxidoreductase deficiency
Lin, J., Zheng, J., Nie, M., Mao, J., & Wang, X. (2017) · Zhonghua neifenmi daixie zazhi · doi:10.3760/cma.j.issn.1000-6699.2017.01.012 · Cited by 3 · see citing works
SATO, T. A., Ishii, T., Fukami, M., Ogata, T., & Hasegawa, T. (2022) · Congenital Anomalies · doi:10.1111/cga.12464 · Cited by 3 · see citing works
Feng, M., 伍学焱, 聂敏, 卢琳, 卢双玉, & 陆召麟 (2009) · Zhonghua yixue zazhi · doi:10.3760/cma.j.issn.0376-2491.2009.46.016 · Cited by 1 · see citing works
Flagged first, then by citations
2 of the 25 references couldn’t be matched to a known paper.
Research works printed but not linked: 4
- [19]Mao J Nie M Gao J Xu H Lu S Wu X.. P450 oxidorerductase deficiency: clinical manifestations and prenatal diagnosis by amniocentesis. Basic Clin Med (2013) 33(1): 24–7. doi: 10.16352/j.issn.1001-6325.2013.01.020 · DOI
- [20]Wang C Jiaxin Y Qinjie T. Cytochrome P450 oxidoreductase deficiency with ovarian flavinized cysts: a case report. J Reprod Med (2014) 23(4): 325–7. doi: 10.3969/j.issn.1004-3845.2014.04.015 · DOI
- [22]Wang X Bai Y Li J Liu J Li Y Guan H. Homozygous mutation of R457H in POR gene which cause P450 oxidoreductase deficiency: a case report and review of the literatures. Int J Endocrinol Metab (2017) 37(03): 213–6. doi: 10.3760/cma.j.isss.1673-4157.2017.03.019 · DOI
- [24]Zhan Y Cheng L Xiong M Zhang J Chen B. Congenital adrenal hyperplasia due to cytochrome P450 oxidoreductase gene mutation: a case report. Chin J Perinatal Med (2018) 21(12): 825–9. doi: 10.3760/cma/j.issn.1007-9408.2018.12.007 · DOI
Cited by
Sorted by citations
Rare forms of congenital adrenal hyperplasia
Tosun, B. G., & Güran, T. (2023) · Clinical Endocrinology · doi:10.1111/cen.15009 · Cited by 22 · see citing works
Zhang, C., Zhao, Z., Du, Y., Huang, Q., Liu, Y., Fu, G., & Xu, J. (2026) · Frontiers in Endocrinology · doi:10.3389/fendo.2026.1791297
Yang, Y., Gao, M., Wu, W., Sun, M., & Wang, Z. (2024) · Research Square · doi:10.21203/rs.3.rs-5267458/v1
Human P450 oxidoreductase deficiency
Pandey, A. V., Barata, I. S., & Flück, C. E. (2025) · Elsevier eBooks · doi:10.1016/b978-0-443-13825-6.00259-4
«Gestational Hyperandrogenism»: Clarifying Terminology and Practical Management
Lepeshkina, L. I., Vorotnikova, S. Y., & Mel'nichenko, G. A. (2026) · Bulletin of Reproductive Health · doi:10.14341/brh12777
Demirel, O. B., Yıldız, M., Küçükgergin, C., Karaman, V., Kılınç, S., Arık, S. D., Gedikbaşı, A., Yıldırım, Z. Y., Ayaz, N. A., Toksoy, G., et al. (2026) · European Journal of Endocrinology · doi:10.1093/ejendo/lvag030
A Two-Step LC-MS/MS method to differentiate 21OHD and PORD in Screen-Positive newborns
Nakatani, H., Watanabe, K., Tsuji‐Hosokawa, A., Sutani, A., Saito, Y., Kirino, S., Yamano, H., Orimoto, R., Gau, M., Yogi, A., et al. (2026) · Endocrine · doi:10.1007/s12020-026-04573-z
Clinical and genetic spectrum of cytochrome P450 oxidoreductase deficiency in Chinese patients
Wang, T., Li, C., Han, C., Zhao, Y., Qi, G., & Zheng, L. (2026) · Endocrine Connections · doi:10.1530/ec-26-0247
Zhang, W., Zeng, J., Li, Y., Xie, C., Sun, Z., Lyu, G., Yan, T., & Huang, X. (2026) · Frontiers in Endocrinology · doi:10.3389/fendo.2026.1896956
Self-citationMolecular Genetic Aspects of Hyperandrogenism
Osinovskaya, N. S., Lazareva, T. E., Kruglova, E. E., Glavnova, O. B., Yarmolinskaya, M. I., Nasykhova, Y. A., & Glotov, A. S. (2026) · Cell and Tissue Biology · doi:10.1134/s1990519x26600882
- Authors
- Zhang, J., Woo, K. L., Hai, Y., Wang, S., Lin, Y., Huang, Y., Peng, X., Wu, H., Zhang, S., Yan, L., & Li, Y.
- Affiliations
- Sun Yat-sen University (CN)
- Corresponding author
- Zhang, Jin
- Venue
- Frontiers in Endocrinology
- Publisher
- Frontiers Media SA
- Published
- 2022-11-28
- Volume
- 13
- Pages
- 1020880-1020880
- ISSN
- 1664-2392 (ISSN-L)
- PMC
- PMC9742467
- OpenAlex
- W4310249268
- Cited by
- 10
- References
- 25
- Citations by year
- 2026: 7 · 2025: 1 · 2024: 1 · 2023: 1
- FWCI
- 0.24
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Frontiers in Endocrinology (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Sexual Differentiation and Disorders
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adrenal Hormones and Disorders
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Clinical Biochemistry › Metabolism and Genetic Disorders
- Keywords
- congenital adrenal hyperplasia, P450 oxidoreductase deficiency, clitoromegaly, autosomal recessive inheritance, heterozygous mutation, infertility, prenatal diagnosis, genetic testing, steroid metabolism, misdiagnosis, bone malformations
- MeSH terms
- Adrenal Hyperplasia, Congenital, Adult, Child, Female, Humans, Infant, Newborn, Male, Oxidoreductases, Pregnancy, Disorders of Sex Development, Virilism, Antley-Bixler Syndrome Phenotype
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