46,XX DSD and Antley-Bixler syndrome due to novel mutations in the cytochrome P450 oxidoreductase gene.

Abstract

Deficiency of the enzyme P450 oxidoreductase is a rare form of congenital adrenal hyperplasia with characteristics of combined and partial impairments in steroidogenic enzyme activities, as P450 oxidoreductase transfers electrons to CYP21A2, CYP17A1, and CYP19A1. It results in disorders of sex development and skeletal malformations similar to Antley-Bixley syndrome. We report the case of a 9-year-old girl who was born with virilized genitalia (Prader stage V), absence of palpable gonads, 46,XX karyotype, and hypergonadotropic hypogonadism. During the first year of life, ovarian cyst, partial adrenal insufficiency, and osteoarticular changes, such as mild craniosynostosis, carpal and tarsal synostosis, and limited forearm pronosupination were observed. Her mother presented severe virilization during pregnancy. The molecular analysis of P450 oxidoreductase gene revealed compound heterozygosis for the nonsense p.Arg223*, and the novel missense p.Met408Lys, inherited from the father and the mother, respectively.

• Authors: Guilherme Guaragna-Filho, Carla Cristina Telles de Sousa Castro, Rodrigo Ribeiro De Carvalho, Fernanda Borchers Coeli, Lúcio Fábio Caldas Ferraz, Reginaldo José Petroli, Maricilda Palandi De Mello, Letícia Esposito Sewaybricker, Sofia Helena Valente Lemos-Marini, Lilia Freire Rodrigues D'Souza-Li, Márcio Lopes Miranda, Andréa Trevas Maciel-Guerra, Gil Guerra-Junior
• Journal: Arquivos brasileiros de endocrinologia e metabologia (Arq Bras Endocrinol Metabol) Vol. 56 Issue 8 Pg. 578-85 (Nov 2012) ISSN: 1677-9487 [Electronic] Brazil
• PMID: 23295302 (Publication Type: Case Reports, Journal Article)

Chemical References

• NADPH-Ferrihemoprotein Reductase

Topics

• Antley-Bixler Syndrome Phenotype (genetics)
• Child
• Female
• Gonadal Dysgenesis, 46,XX (genetics)
• Heterozygote
• Humans
• Mutation (genetics)
• NADPH-Ferrihemoprotein Reductase (genetics)