Endocrine Abstracts

JOINT1883

Introduction: Cytochrome P450 oxidoreductase deficiency (PORD) is a rare form of congenital adrenal hyperplasia. This study reports the first case diagnosed with PORD presenting with uterine didelphys, vaginal atresia, and right renal agenesis. A comprehensive literature review was performed to analyze Müllerian duct, pubertal development, and fertility outcomes in 46,XX patients.

Case presentation and literature review: A 3-year-and-10-month-old Chinese female presented with ambiguous genitalia, accompanied by a history of maternal virilization during pregnancy. The patient exhibited midface hypoplasia and arachnodactyly, along with Antley-Bixler syndrome (ABS)-like skeletal malformations, in addition to ambiguous genitalia characterized by clitoromegaly, labial fusion, and a single urogenital sinus. Laboratory evaluation revealed a 46,XX karyotype, mildly elevated adrenocorticotropic hormone, normal cortisol, significantly elevated 17-hydroxyprogesterone, and reduced androstenedione and dehydroepiandrosterone. Pelvic ultrasonography demonstrated the presence of didelphic uterus, double cervix, vaginal atresia, and right renal agenesis. Whole-exome sequencing identified a homozygous p.R457H missense variant in the POR gene, confirming the diagnosis of PORD. A review of 38 reported cases of 46,XX patients revealed a potential association between maternal virilization during pregnancy and the disorders of sex development in affected individuals. The p.R457H and p.A287P variants are the most commonly reported variants. The p.R457H variant is predominantly identified in Asian populations, while the p.A287P variant is frequent observed in Caucasian patients, and is often associated with more severe ABS-like skeletal malformations. Among patients with PORD, pubertal development may occur, however, breast development and menarche often follow irregular patterns, contributing to challenges in achieving natural conception during their reproductive years. Additionally, structural anomalies of the Müllerian ducts may represent a rare phenotype of the condition.

Conclusion: This review suggests that uterine malformations and unilateral renal agenesis may represent uncommon phenotypes of PORD. Early initiation of glucocorticoid replacement therapy and timely estrogen supplementation not only reduce the risk of adrenal crises but also serve as effective measures to inducing pubertal development and decrease the recurrence of ovarian cysts, which may, in turn, positively influence fertility preservation in the future.