P450 oxidoreductase (POR) enzyme deficiency is a rare form of congenital adrenal hyperplasia, characterized by combined and partial impairments in steroidogenic enzymes. It may be associated with Antley-Bixler syndrome.
Here we report a newborn with ambiguous genitalia, skeletal malformations, and adrenal insufficiency who was diagnosed with Antley-Bixler syndrome.
A 12-day-old newborn presented with ambiguous genitalia. She was born small for gestation age with a birth weight of 2 400 g at 38 weeks of gestation to a non-consanguineous couple. The pregnancy was uneventful except for maternal voice deepening. Her weight was 2 350 g (-1.99 SDS), her length was 49 cm (-0.12 SDS), and head circumference was 32.5 cm (-1.47 SDS). She had prominent eyeballs, frontal bossing, dysplastic ears, bilateral upper extremity contractures, left choanal stenosis, and genital virilization (Prader stage 3) with 1 cm phallus and bilaterally non-palpable gonads.
Adrenocorticotropic hormone test showed adrenal insufficiency with a low cortisol peak (6 mcg/dL) and high 17-OH progesterone peak (50 ng/mL). Her karyotype was 46,XX. Bilateral ovarian cysts were detected on ultrasound imaging. These findings suggested POR deficiency and Antley-Bixler syndrome. The molecular genetic analysis of POR gene revealed a novel compound heterozygous mutation (IVS3-1 G>A (c.238-1 G>A)/c.929_937delTCTCGGACT). Both parents were heterozygous for these mutations.
POR deficiency should be considered in patients with congenital adrenal hyperplasia with a history of maternal virilization during pregnancy and these patients should be evaluated for the presence of skeletal malformations.