Cytochrome P450 Oxidoreductase Deficiency PORD: A Case Report

Background: A rare and the newest form of congenital adrenal hyperplasia is Cytochrome P450 oxidoreductase deficiency (PORD). There has been close to 100 cases reported.

Objective: We report a case of a newborn with several characteristic features of POR deficiency.

Case description: Patient is a full term new born product of first pregnancy of an 18 year old mother. Pregnancy uncomplicated, normal estradiol on second trimester screening, mother report increased acne. Delivered via C-section due to failure to progress of labor, APGAR 2, 5, 5 at 1, 5 and 10 min, respectively. Small for age, weigh 2.726 Kg (99^th percentile) anterior fontanelle, down slanting palpebral fissures, proptosis, Long palpebral fissures, up turned nose, Flat nasal bridge, retronagtia, large tongue. Microphallus 1.5cm (<5^th percentile) with hypospadias with urethral opening located in the glans, testicles descended. Elbows in fixed position. Second toe this longer than 1^st. Increased separation between 1^st and 2^nd toe, 3rd, 4th, and 5th short. Unremarkable family history with no consanguinity. X-ray demonstrated bilateral Radio-humeral synostosis. Intravenous 250 mg Cosyntropin stimulation test with Cortisol 6.7 ug/dL and 15.1 ug/dL at 0 min and 60 min. No cardiovascular, electrolytes or glucose abnormalities. Sanger sequencing of the POR gene demonstrated two pathogenic variants c.859G>C(p.Ala287Pro) and c.651_653del (p.Glu217del.)

Conclusion: We demonstrated several features, as well two pathogenic variants in compound heterozygous state of P450 Oxidoreductase (POR) gene in an individual with blunt cortisol production that might require steroid supplementation during stress, as was advised in this case.