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.

摘要

11β-羟化酶缺乏是继21-羟化酶缺乏导致先天性肾上腺增生（CAH_11β）的第二大常见酶失调。在女性中, CAH_11β经典形式的临床表型与不明确的生殖器、女性男性化以及高血压相关, 而较轻微的非经典形式的最常见的主诉包括多毛症、痤疮、月经不调和不孕症。在此, 我们介绍了患有11β-羟化酶缺乏、高血压和不孕症的成年女性的临床和遗传特征, 她从第一次怀孕到绝经早期都接受了随访。患者的遗传分析揭示了由于CYP11B1基因p.Val316Met和p.Asp480ThrfsTer2两个突变体引起的化合物杂合性。以前的文献中没有报道这两种突变是致病性的。关于非经典CAH_11β患者的临床管理、生育能力、矿物质肾上腺皮质激素异常和围绝经期转变等新问题也进行了简要讨论。本文所展示的CAH_11β成年女性病例表明, 对不同CAH形式的患者进行正确诊断和密切监测可确保良好的治疗依从性和成功的生育。

Keywords:

• 11β-hydroxylase deficiency
• congenital adrenal hyperplasia
• fertility
• menopause
• genetic variant

Disclosure statement

No potential conflict of interest was reported by the authors.