Clinical Characteristics and Molecular Aetiology of Cytochrome P450 Oxidoreductase Deficiency Diagnosed in 46 XX Patients

Abstract Background P450 oxidoreductase deficiency (PORD) affects cytochrome enzyme activities, causing various symptoms, such as adrenal insufficiency, disorders of sex development and skeletal malformations. This study aims to elucidate the clinical manifestations, genotype characteristics, diagnosis and management of 46 XX karyotype patients with PORD in China. Method The patients’ clinical characteristics were summarized based on manifestations, hormone profiles, and responses to treatments. Seven patients aged between 11 and 19 years were included in the series from 2004 to 2022 in a tertiary medical centre. Result All patients presented ovarian multilocular cysts and different manifestations of skeletal malformation. Patients after puberty all suffered from abnormal menses. Five patients’ external genitalia exhibited virilizing patterns, and three had received perineoplasty. The hormone analyses of six patients indicated hypergonadotropic hypogonadism, while all patients’ progesterone and deoxycorticosterone levels were elevated. The most frequent POR mutation, c.1370G > A, is located on exon 11 and appears in all seven patients with an allele frequency of 92.9% (13/14). One case was a carrier of a novel variance (c.1684dupG), situated within exon 14, encoding a nonsense mutation in the NADPH binding area. Conclusion Therefore, c.1370G > A could be a dominant mutation type of PORD in China. Female patients with PORD have a vulnerable ovarian reserve, and their ovarian macrocysts can be managed conservatively for fertility preservation. This study specifically focuses on PORD in 46 XX Chinese individuals, which implies its genetic causes with novel genetic findings and summarizes patients’ puzzling spectrum of clinical manifestations.