Mini Review

Genetic and Clinical Features of P450 Oxidoreductase Deficiency
Rachel R. Scott^a, Walter L. Miller<sup>b

a</sup>Division of Endocrinology, Department of Paediatrics, IWK Health Centre, Dalhousie University, Halifax, N.S., Canada;
^bDivision of Endocrinology, Department of Pediatrics, University of California, San Francisco, Calif., USA

Address of Corresponding Author

Horm Res 2008;69:266-275 (DOI: 10.1159/000114857)

  Key Words

• Adrenal
• steroidogenesis
• Craniosynostosis
• Antley-Bixler syndrome
• Ambiguous genitalia
• FGFR2 mutations
• Adrenal steroidogenesis

  Abstract

P450 oxidoreductase (POR) deficiency is an autosomal recessive disorder of steroidogenesis with multiple clinical manifestations. POR is the electron donor for all microsomal P450 enzymes, including the three steroidogenic enzymes P450c17 (17-hydroxylase/17,20-lyase), P450c21 (21-hydroxylase), and P450aro (aromatase). Since the first description of POR mutations in 2004, about 50 patients have been reported. Serum steroid profiles indicate partial deficiencies in 21-hydroxylase, 17-hydroxylase and 17,20-lyase. The 17-OH progesterone levels are elevated, as in 21-hydroxylase deficiency, while androgen levels are low; cortisol may be normal but is poorly responsive to adrenocorticotropic hormone. Most patients also have associated skeletal malfor- mations (craniosynostosis, radio-ulnar synostosis, midface hypoplasia, bowed femora) termed Antley-Bixler syndrome. Antley-Bixler syndrome with normal steroidogenesis is caused by autosomal dominant gain-of-function mutations in fibroblast growth factor receptor 2. Males with POR deficiency are often undervirilized, while females can be virilized. The prognosis for patients with POR deficiency appears to depend on the severity of the bony malformations and their timely treatment. The potential impact of POR mutations on drug metabolism by other hepatic P450 enzymes requires further investigation. Given the varied physical and biochemical phenotype of POR deficiency and the risk of adrenal insufficiency, clinicians should be alert to this potential diagnosis.

Copyright © 2008 S. Karger AG, Basel

  Author Contacts

Dr. Rachel Scott
IWK Health Centre
5850/5980 University Avenue
Halifax, N.S. B3K 6R8 (Canada)
Tel. +1 902 470 8707, Fax +1 902 470 7264, E-Mail rrscott@dal.ca

  Article Information

Received: August 6, 2007
Accepted: September 19, 2007
Published online: February 6, 2008
Number of Print Pages : 10
Number of Figures : 3, Number of Tables : 2, Number of References : 61