ESPE Abstracts

Background: POR deficiency is a rare form of congenital adrenal hyperplasia, transmitted in an autosomal recessive trait, that is characterized by ambiguous genitalia, impaired steroidogenesis and skeletal malformations similar to those of Antley-Bixler syndrome. It is caused by mutations in the P450 oxidoreductase gene (POR), an electron donor for all microsomal P450 enzymes including the three steroidogenic enzymes P450c 17 (17 alfa-hidroxylase /17,20 lyase), P 450c21 (21-hydroxylase) and P450 aro (aromatase). To date, more than 140 PORD cases have been reported worldwive.

Case presentation: We report the case of a Roumanian baby that was reffered to our pediatric endocrinology department soon after birth (day 6) for the investigation of ambiguous genitalia. She was diagnosed in utero with skeletal abnormalities and the genetic tests excluded osteogenesis imperfecta. The antenatal caryotype was 46,XX. She was the first child of a healthy unrelated couple delivered by cesarean at 39 week. It is noteworthy that the mother, developed a deepening of her voice during pregnancy. The clinical examination revealed facial dysmorphism: large domed forehead, flat nose and midface hypoplasia, hypertelorism, dysplastic ears, stenotic external auditory canals, short and deep philtrum, lips bifidas, limited movement of the elbows and metacarpophalangeal joints, arachnodactyly, thenar and hipothenar muscle atrophy, bowing of lower extremities with limited movement. External genitalia were severy virilized (Prader stage 5) with a phallus like structure of 2.0 cm long and complete labial fusion, the meatus opened at the tip of the phallus-like structure. Serum steroid profiles indicated elevated androgen precursors (17-OH-pregnenolone and 17-OH-progesterone) with normal adrenal androgens (dehydroepiandrosterone sulfate and androstendione), high baseline adrenocorticotrophic hormone (ACTH) with normal serum cortisol, low estradiol. Adrenal insufficiency was detected by corticotropin stimulation test. Wholebody X-Ray showed bilateral femoral deformations (bent femur) and radiohumeral synostosis. Abdominal ultrasound was normal. The diagnosis of PORD was suspected on clinical background (Antley-Bixler phenotype, ambigous genitalia) together with the hormonal profile and the patient was referred to the clinical genetician for genetic confirmation. The patient started replacement therapy with hydrocortisone 7 mg/m2.

Conclusions: PORD is a very rare disease that needs to be suspected in patients with disorder of sexual development especially when combined with skeletal deformities. It is possible that PORD remains undiagnosed in some patients. Molecular analysis of the POR gene is crucial for making correct diagnosis. With careful airway management, many children with ABS survive and the prognosis may be reasonably good