Long-term follow-up of a female patient with non-classical 11β-hydroxylase deficiency and two novel mutations in CYP11B1

Abstract

11β-Hydroxylase deficiency is the second most common enzyme disorder after 21-hydroxylase deficiency causing congenital adrenal hyperplasia (CAH_11β). In females, the clinical phenotype of CAH_11β classic forms is associated with ambiguous genitalia, virilization and hypertension, while most common complaints in milder non-classic forms include hirsutism, acne, menstrual disturbances, and infertility. Herein, we present clinical and genetic characteristics of an adult woman with 11β-hydroxylase deficiency, hypertension and infertility; she has been followed up from her first pregnancy to her early menopause. Genetic analyses of the patient revealed a compound-heterozygosity due to two variants in the CYP11B1 gene p.Val316Met and p.Asp480ThrfsTer2. Both mutations have not been previously reported as pathogenic in the literature. Emerging questions concerning the clinical management, fertility potential, mineral corticoid abnormalities and perimenopausal transition in patients with non-classic CAH_11β have also been briefly discussed. The presented case of an adult woman with CAH_11β shows that the proper diagnosis and close monitoring of patients with different CAH forms might ensure good therapy adherence and successful fertility.

Keywords: 11β-hydroxylase deficiency; congenital adrenal hyperplasia; fertility; genetic variant; menopause.