Case Report: Integrating clinical presentation and genetic analysis in P450 oxidoreductase deficiency: a novel...

Cytochrome P450 oxidoreductase deficiency (PORD) is an ultra-rare autosomal recessive disorder caused by mutations in the POR gene and characterized by highly heterogeneous skeletal, genital, and endocrine manifestations. Owing to this complexity, PORD remains frequently underrecognized in clinical practice, and integrated clinical-genetic syntheses remain limited.

A retrospective analysis was conducted on the clinical data of a PORD patient treated at Shenzhen Children's Hospital. Relevant literature was retrieved from PubMed, Web of Science, and China National Knowledge Infrastructure (CNKI). Reported cases were analyzed with respect to sex, age, geographic distribution, clinical manifestations, and POR gene variants.

The patient from our hospital, a 7-month-old infant, presented with characteristic features including frontal bossing, craniosynostosis, flat nasal bridge, proximal radioulnar synostosis, clitoromegaly, partial labial fusion, and steroid hormone abnormalities. Genetic testing identified compound heterozygous variants, p.G146fs*111, a novel mutation, and p.R457H. The patient underwent bilateral mandibular distraction osteogenesis and cranial reconstruction, which alleviated airway obstruction, swallowing difficulty, and craniosynostosis. A total of 50 eligible studies were identified, comprising 167 patients (male:female = 77:90). The major clinical findings were skeletal deformities in 124 cases (74.25%), gonadal deformities in 121 (72.46%), hormonal abnormalities or delayed puberty in 127 (76.05%), and adrenal insufficiency or crisis in 108 (64.67%). Additionally, ovarian cysts were observed in 36 female patients (40.00%). Among all patients, the allele frequency of the p.R457H variant was 27.25%, while that of the p.A287P variant was 14.97%. In the 22 Chinese patients, the allele frequency of the p.R457H variant reached 38.64%.

We report the clinical features of a PORD patient carrying a novel POR mutation, p.G146fs*111. PORD typically presents with skeletal and genital malformations as well as adrenal insufficiency. Management requires multidisciplinary collaboration, including individualized steroid replacement, regular blood pressure monitoring, and surgical intervention when necessary. The p.R457H variant may represent a hotspot mutation in East Asian populations.