The CYP19A1 gene product cP450aromatase enzyme is responsible for estrogen synthesis and androgen/estrogen equilibrium in many tissues; placenta and gonads are being the leading tissues. cP450aromatase deficiency has important effects on clinical phenotype due to excessive amount of androgen accumulation and insufficient estrogen synthesis in the pre- and postnatal periods. We identified a new point mutation in the CYP19A1 gene causing aromatase deficiency in three Turkish families. Here, we report three causins carrying this mutation. Three cases with the current chronological ages of 12.3 (case I), 5 (case II) and 2 (case III) years applied to Pediatric Endocrinology Department because of ambigious genital structures in the newborn period. Virilizing signs such as severe acne formation, voice deepening and clitoral enlargement during pregnancy were defined in the maternal history and physical examination. CYP19A1 gene analysis was performed with the preliminary diagnosis of cP450arom deficiency in three cases, and five parents, who were cousins. It was observed that 568insC mutation detected at the fifth exon, caused codon stop, so a nonfunctional product with 200 amino acids without the heme region, which was the requirement for the enzymatic activity, was formed, and the cases were homozygote for this newly defined mutation whereas parents were heterozygote. During their follow ups, ovarian dimensions and LH, FSH, testosterone, and estradiol measurements of cases I and II were detected at the prepubertal levels. In the case III, ovaries could not be shown by neither ultrasonography nor MRI, and hormonal data were consistent with the age. Aromatase deficiency is a very rare autosomal recessive disorder there are only a limited number of case reports in the literature. The mutation detected in three Turkish families was a novel mutation. Concomitance of maternal virilization is the most important striking signal for aromatase deficiency in a virilized female baby.
20 - 22 Sep 2014
European Society for Paediatric Endocrinology