IMPE Abstracts

Congenital adrenal hyperplasia (CAH) is a monogenic autosomal recessive disorder that may involve different steroidogenic enzymes. POR (P450 oxidoreductase) deficiency is a rare variant of unknown incidence and is the most complex form of CAH. POR is an electron-donating enzyme for CYP17A1, CYP21A2, and CYP19A1. Clinically it can be observed as a combined deficiency of CYP17A1, CYP21A2, and secondary to the donating defect to aromatase, the mother can become virilized during pregnancy. Patients with this defect may present a phenotype compatible with Antley Bixler syndrome. We describe a case of a 2-month-old patient, a child of consanguineous parents, who presented deformity of both legs at birth, wide forehead, nose with low nasal bridge, dysplastic ears, phallus 1.5 cm, smooth labioscrotal folds without hyperpigmentation, without palpable gonads and bilateral inguinal hernia, incomplete extension of the elbow and ankles. The radiographic study showed the presence of bilateral femoral fracture and craniosynostosis and the mother became virilized during pregnancy. The patient's karyotype was 46,XY and laboratory tests showed at 58 days of birth: LH 0.21 mIU/mL, FSH 5.2 mIU/mL and testosterone <0.07 ng/mL. The ACTH test was performed at 2.5 months of age showing decreased basal cortisol without response to ACTH. The basal and post-ACTH steroids are described in the table, these are compatible with a combined 21 and 17-hydroxylase deficiency. A molecular study revealed a homozygous pathogenic variant in the POR p.Ala287Pro gene. The patient is now 13 months old in good condition and he is receiving hydrocortisone at a dose of 8 mg/m2/day. We describe, to our knowledge, the first case reported with a homozygous p.Ala287Pro variant, that presents sub-virilization. All the steroids were measured by LC-MS/MS: