Ann Pediatr Endocrinol Metab.  2020 Jun;25(2):97-103. 10.6065/apem.1938152.076.

Clinical, endocrinological, and molecular features of four Korean cases of cytochrome P450 oxidoreductase deficiency

• Lee Y
• Choi JH
• Oh A
• Kim GH
• Park SH
• Moon JE
• Ko CW
• Cheon CK
• Yoo HW

• KMID: 2503360
• DOI: http://doi.org/10.6065/apem.1938152.076

Abstract

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.

Keyword

Cytochrome P450 oxidoreductase deficiency; Disorders of sex development

Figure

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  Fig. 1. Radiological findings for subject 4. (A) Skull radiography shows hypoplasia of midfacial bones and early fusion of cranial bones. (B) Scoliosis was found in whole spine radiography. (C, D) Elbow radiography shows radiohumeral synostosis of both arms. R, right; L, left; A-P, anteroposterior.

Reference

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