A report of congenital adrenal hyperplasia due to 17α-hydroxylase deficiency in two 46,XX sisters

Abstract

Congenital adrenal hyperplasia (CAH) is a group of rare orphan disorders caused by mutations in seven different enzymes that impair cortisol biosynthesis. The 17α-hydroxylase deficiency (17OHD) is one of the less common forms of CAH, corresponding to approximately 1% of the cases, with an estimated annual incidence of 1 in 50,000 newborns. Cases description – two phenotypically female Ecuadorian sisters, both with primary amenorrhea, absence of secondary sexual characteristics, and osteoporosis. High blood pressure was present in the older sister. Hypergonadotropic hypogonadism profile was observed: decreased cortisol and dehydroepiandrosterone sulfate (DHEAS), increased adrenocorticotropic hormone (ACTH) and normal levels of 17-hydroxyprogesterone, extremely high deoxycorticosterone (DOC) levels, and a tomography showed bilateral adrenal hyperplasia in both sisters. Consanguinity was evident in their ancestors. Furthermore, in the exon 7, the variant c.1216T > C, p.Trp406Arg was detected in homozygosis in the CYP17A1 gene of both sisters. We report a homozygous missense mutation in the CYP17A1 gene causing 17OHD in two sisters from Loja, Ecuador. According to the authors, this is the first time such deficiency and mutation are described in two members of the same family in Ecuador.

摘要

先天性肾上腺增生(CAH)是一组罕见的孤儿疾病, 由七种不同酶的突变引起, 这些酶可以损害皮质醇的生物合成。17a-羟化酶缺乏症(17OHD)是CAH的一种不常见形式, 约占病例的1%, 估计每年发病率为50000名新生儿中有1名。病例描述-两个表型女性的厄瓜多尔姐妹, 都有原发性闭经, 缺乏第二性征, 并患有骨质疏松。姐姐患有高血压。观察到高促性腺激素性性腺功能减退症的特征：皮质醇和硫酸脱氢表雄酮(DHEAS)降低, 促肾上腺皮质激素(ACTH)升高, 17-羟孕酮(17-羟孕酮)正常, 极高的去氧皮质酮(DOC)水平, X线断层扫描显示两姐妹双侧肾上腺增生。他们的上一辈有明显的血缘关系。此外, 在第7外显子中, 在两姐妹的CYP17A1基因中均检测到了c.1216T>C, p.Trp406Arg突变。我们报告了来自厄瓜多尔洛哈的两个姐妹CYP17A1基因的纯合错义突变导致17OHD。据作者说, 这是厄瓜多尔首次在同一个家庭的两个成员中描述这种缺陷和突变。

The Chinese abstracts are translated by Prof. Dr. Xiangyan Ruan and her team: Beijing Obstetrics and Gynecology Hospital, Capital Medical University, Beijing 100026, China.

Keywords:

• Congenital adrenal hyperplasia
• 17 alpha hydroxylase deficiency
• sisters
• consanguineous family

Acknowledgements

We thank our patients who accepted to participate in this study. We also thank Dr. Luis Freire S, the ophthalmologist who approached the patients, and Dr. Esteban Peghini, the radiologist who supported in the interpretation and selection of the images. We thank Melissa Hidalgo, Pamela Benavídes and Alexis Guijarro, Universidad de las Américas (UDLA) Medical students who supported in logistics aspects during medical appointments of the sisters. A special acknowledgment to Tannya Lozada, PhD, Chief of Research Department in UDLA, who supported us throughout the whole process. Finally, we thank María Eugenia Sánchez, a researcher, who performed the initial karyotype in the Biomedical Sciences Institute at UDLA.

Disclosure statement

No potential conflict of interest was reported by the authors.

Additional information

Funding

This work was supported by Universidad de las Américas (Grant number MED.FE.17.03).