Congenital adrenal dysfunction caused by Зр-hydroxysteroid dehydro-genase deficiency: molecular genetic diagnosis and clinical manifestations in two sibs of different sexes

Abstract

Зb-hydroxysterold dehydrogenase (3beta HSD) deficiency is a rare form of congenital adrenal conical dysfunction (CA CD) that accounts for not more 1% in the tatter's pattern and that is manifested by glucocorticoid and minerolocorticoid deficiencies. In this type of CACD, conversions of pregnenolone to progesterone, of 17-hydroxypregnenolone to 17-hydroxyprogesterone, and of dehydroepian-drosterone to androstenedione are impaired. HSD3B2 gene defect underlies this disease. The results of examination and treatment of 2 patients with 3beta HSD deficiency are first presented in the Russian literature. The diagnosis of3beta HSD deficiency was established in a 13-year-old girl and an 8-month boy. In both patients, the disease was manifested by the symptoms of severe adrenal insufficiency. Moderate external genital virilization had been noted in the girl since birth whereas the boy had manifestations of false male hermaphroditism. Molecular genetic study revealed earlier unknown homozygous nonsense mutation W230X in the HSD3B2 gene. Our observations emphasize it necessary to include 3beta HSD deficiency into the algorithm of differential diagnosis of CACD in patients with atypical manifestations of CACD particularly when the latter Is concurrent with false male hermaphroditism. By taking into account the fact that there are unavailable hormonal verification methods, molecular genetic studies are prominent in the diagnosis of this disease.