Clinical, endocrinological, and molecular features of four Korean cases of cytochrome P450 oxidoreductase deficiency
Open accessAbstract
PURPOSE: Cytochrome P450 oxidoreductase (POR) deficiency is a rare autosomal recessive disorder caused by mutations in the POR gene encoding an electron donor for all microsomal P450 enzymes. It is characterized by adrenal insufficiency, ambiguous genitalia, maternal virilization during pregnancy, and skeletal dysplasia. In this study, we investigated the clinical, hormonal, and molecular characteristics of patients with POR deficiency in Korea. METHODS: This study included four patients with POR deficiency confirmed by biochemical and molecular analysis of POR. Clinical and biochemical findings were reviewed retrospectively. Mutation analysis of POR was performed by Sanger sequencing after polymerase chain reaction amplification of all coding exons and the exon-intron boundaries. RESULTS: All patients presented with adrenal insufficiency and ambiguous genitalia regardless of their genetic sex. Two patients harbored homozygous p.R457H mutations in POR and presented with adrenal insufficiency and genital ambiguity without skeletal phenotypes. The other two patients with compound heterozygous mutations of c.[1329_1330insC];[1370G>A] (p.[I444Hfs*6];[R457H]) manifested skeletal abnormalities, such as craniosynostosis and radiohumeral synostosis, suggesting Antley-Bixler syndrome. They also had multiple congenital anomalies involving heart, kidney, and hearing ability. All patients were treated with physiologic doses of oral hydrocortisone. CONCLUSION: We report the cases of 4 patients with POR deficiency identified by mutation analysis of POR. Although the study involved a small number of patients, the POR p.R457H mutation was the most common, suggesting founder effect in Korea. POR deficiency is rare and can be misdiagnosed as 21-hydroxylase or 17α-hydroxylase/17,20-lyase deficiency. Therefore, molecular analysis is critical for confirmatory diagnosis.
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POR transfers electrons from NADPH to more than 50 microsomal CYP enzymes.
“It transfers electrons from nicotinamide adenine dinucleotide phosphate (NADPH) to more than 50 microsomal cytochrome P450 (CYP) enzymes (4–6).”
From Case Report: Integrating clinical presentation and genetic analysis in P450 oxidoreductase deficiency: a novel mutation and systematic review (2026) · cites this paper as [5]
The Introduction describes POR as an electron donor for all microsomal P450 enzymes, supporting the electron-transfer role. Our copy does not specify NADPH as the electron source or give the figure of more than 50 enzymes. (LLM, conf=0.86)
Experimental — accuracy not yet measuredThe POR protein comprises 680 amino acids and functions as an essential electron donor.
“The cytochrome P450 oxidoreductase (POR) protein, comprising 680 amino acids, functions as an essential electron donor.”
From Case Report: Integrating clinical presentation and genetic analysis in P450 oxidoreductase deficiency: a novel mutation and systematic review (2026) · cites this paper as [5]
The Introduction states that the POR gene encodes an electron donor for all microsomal P450 enzymes, supporting the functional part of the claim. Our copy does not state that the POR protein comprises 680 amino acids; a search for that number and for protein length found no supporting passage. (LLM, conf=0.88)
Experimental — accuracy not yet measuredp.R457H is a common pathogenic variant in East Asian populations.
“Together, these findings strongly suggest that p.R457H is a common pathogenic variant in East Asian populations.”
From Case Report: Integrating clinical presentation and genetic analysis in P450 oxidoreductase deficiency: a novel mutation and systematic review (2026) · cites this paper as [5]
The Results (Molecular analysis of the POR gene) identify p.R457H as pathogenic and report it in 6 of 8 alleles among four Korean patients with POR deficiency. The Discussion also notes that all Korean cases described there carried it. These small patient series do not establish that the variant is common across East Asian populations. (LLM, conf=0.88)
Experimental — accuracy not yet measuredIn Korea, all six reported PORD cases carried the p.R457H variant.
“In Korea, all six reported PORD cases carried the p.R457H variant (5).”
From Case Report: Integrating clinical presentation and genetic analysis in P450 oxidoreductase deficiency: a novel mutation and systematic review (2026) · cites this paper as [5]
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- Authors
- Lee, Y., Choi, J.-H., Oh, A., Kim, G.-H., Park, S.-H., Moon, J. E., Ko, C. W., Cheon, C.-K., & Yoo, H.-W.
- Affiliations
- Asan Medical Center (KR)
- Kyungpook National University Hospital (KR)
- Pusan National University Children's Hospital (KR)
- Corresponding author
- Yoo, Han-Wook
- ORCID
- Venue
- Annals of Pediatric Endocrinology & Metabolism
- Published
- 2020-06-30
- Volume
- 25
- Issue
- 2
- Pages
- 97-103
- ISSN
- 2287-1012 (ISSN-L)
- 2287-1292
- PMC
- PMC7336261
- OpenAlex
- W3038477489
- Cited by
- 16
- References
- 26
- Citations by year
- 2026: 5 · 2025: 1 · 2023: 5 · 2022: 4 · 2021: 1
- FWCI
- 1.89
- Type
- journal article
- Language
- en
- Open access
- diamond
- doi.org
- Licence
- Locations
- Annals of Pediatric Endocrinology & Metabolism (publishedVersion, cc-by-nc)
- PubMed Central (publishedVersion, cc-by-nc)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- National Research Foundation of Korea (2017R1D1A1B03029638)
- Ministry of Education
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adrenal Hormones and Disorders
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Sexual Differentiation and Disorders
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Clinical Biochemistry › Metabolism and Genetic Disorders
- Keywords
- POR gene, founder effect, adrenal insufficiency, ambiguous genitalia, Antley-Bixler syndrome, craniosynostosis, skeletal dysplasia, compound heterozygosity, hydrocortisone therapy, Korean patients
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