The Prevalence, Molecular Analysis and HLA Typing of Late-onset 21-Hydroxylase Deficiency in Turkish Woman with Hirsutism and Polycystic Ovary

Abstract

We studied the incidence of late-onset congenital adrenal hyperplasia (LOCAH) due to 21-hydroxylase (21-OH) deficiency, its molecular genotype expression, and its association with the major histocompatibility complex in 61 women with hirsutism and polycystic ovary. Ultrasound, clinical and hormonal parameters were used to define polycystic ovary syndrome (PCOS). Baseline and ACTH stimulated 17α-hydroxyprogesterone (17-OHP) levels were measured for screening of LOCAH during follicular phase. Forty-one women were diagnosed as having PCOS (67%) and 20 women were diagnosed as having had LOCAH due to 21-OH deficiency (33%). In LOCAH patients, the most common mutation (Val281-Leu, V281L) was found in 10 patients (7 heterozygous/3 homozygous). The frequency of V281L mutation was found as 32.5% in 20 patients. All patients with the V281L mutation presented HLA-B14 (100%) and six of them presented DR1 (60%), confirming that LOCAH is linked to the histocompatibility complex. Although molecular analysis is a better and more accurate means for an exact and precise definition of LOCAH, it is not routinely available in our country. So, ACTH stimulation test combined with HLA-B14 typing should be more widely utilized in these patients. As a result, LOCAH due to 21-OH deficiency is unexpectedly high in Turkish patients with hirsutism and PCO.