Introduction: P450 oxidoreductase (POR) deficiency is a rare form of congenital adrenal hyperplasia. In both genders, it can lead to ambiguous genitalia, impaired steroidogenesis, and skeletal findings similar to those of Antley-Bixler syndrome.
Cases: We describe two cases of POR deficiency. The first case was an 8.5-year-old girl who was admitted to our clinic due to ambiguous genitalia. Karyotype was 46, XX. There were mild dysmorphic facial findings and mild metacarpophalangeal joint deformity. The patient's basal cortisol and ACTH levels were normal, while 17-hydroxyprogesterone (17OHP) levels were high. Peak cortisol response to the ACTH stimulation test was found to be insufficient. Our second case, a sibling of the first case, was admitted for routine checkup at the age of 15 months. As in our first case, there were dysmorphic facial findings and metacarpophalangeal joint deformity. The genital structure was normal. Karyotype was 46, XY. Basal cortisol and ACTH levels were normal, while 17OHP level was slightly high. Peak cortisol response to the ACTH stimulation test was found to be insufficient. Based on our findings, POR deficiency was considered in both of these cases and NM_000941.3:c.929_937delTCTCGGACT(p.Ile310_Ser313delinsThr) (homozygous) mutation was detected in the POR gene that had not previously been described.
Conclusion: We detected a novel variant in the POR gene in two sibling cases with adrenal insufficiency, dysmorphic face, and mild skeletal findings. While the detected mutation caused ambiguous genitalia in the female case, it did not cause ambiguous genitalia in the male case.
Keywords: Adrenal insufficiency; Congenital adrenal hyperplasia; Disorders of sexual development; POR deficiency; Skeletal malformation.