P450 oxidoreductase deficiency - a new form of congenital adrenal hyperplasia

Flück, Christa E; Pandey, Amit V; Huang, Ningwu; Agrawal, Vishal; Miller, Walter L (2008). P450 oxidoreductase deficiency - a new form of congenital adrenal hyperplasia. Endocrine development, 13, pp. 67-81. Basel: Karger 10.1159/000134826

[img] Text
134826.pdf - Published Version
Restricted to registered users only
Available under License Publisher holds Copyright.

Download (233kB) | Request a copy

Patients with adrenal insufficiency, genital anomalies and bony malformations resembling the Antley- Bixler syndrome (a craniosynostosis syndrome), are likely to have P450 oxidoreductase (POR) deficiency. Since our first report in 2004, about 26 recessive POR mutations have been identified in 50 patients. POR is the obligate electron donor to all microsomal (type II) P450 enzymes, including the steroidogenic enzymes CYP17A1, CYP21A2 and CYP19A1. POR deficiency may cause disordered sexual development manifested as genital undervirilization in 46,XY newborns as well as overvirilization in those who are 46,XX. This may be explained by impaired aromatization of fetal androgens which may also lead to maternal virilization and low urinary estriol levels during pregnancy. A role for the alternate 'backdoor' pathway of androgen biosynthesis, leading to dihydrotestosterone production bypassing androstenedione and testosterone, has been suggested in POR deficiency but remains unclear. POR variants may play an important role in drug metabolism, as most drugs are metabolized by hepatic microsomal P450 enzymes. However, functional assays studying the effects of specific POR mutations on steroidogenesis showed that several POR variants impaired CYP17A1, CYP21A2 and CYP19A1 activities to different degrees, indicating that each POR variant must be studied separately for each potential target P450 enzyme. Thus, the impact of POR mutations on drug metabolism by hepatic P450s requires further investigation.

Item Type:

Journal Article (Further Contribution)


04 Faculty of Medicine > Department of Gynaecology, Paediatrics and Endocrinology (DFKE) > Clinic of Paediatric Medicine > Endocrinology/Metabolic Disorders

UniBE Contributor:

Flück Pandey, Christa Emma, Pandey, Amit Vikram










Amit Vikram Pandey

Date Deposited:

04 Oct 2013 15:03

Last Modified:

02 Mar 2023 23:22

Publisher DOI:


PubMed ID:





https://boris.unibe.ch/id/eprint/27188 (FactScience: 104910)

Actions (login required)

Edit item Edit item
Provide Feedback