Genetic defect of a combined 17 α-hydroxylase/17,20-lyase deficiency patient with adrenal crisis

Abstract

Combined 17 α-hydroxylase/17,20-lyase deficiency (17OHD) is a rare autosomal recessive disease that is a type of congenital adrenal hyperplasia, which results in hypertension, hypokalemia, sexual infantilism, primary amenorrhea in females (46,XX), or pseudohermaphroditism in males (46,XY). It is mainly caused by mutation in the CYP17A1 gene, which encodes a key enzyme in the steroidogenic pathway. However, these patients rarely experience adrenal crisis, due to abnormally high corticosterone levels. Here, we report a 17OHD patient who experienced clinical adrenal crisis on day 1 after gonadectomy. Her (46,XY) genetic defect was c0.715 C > T p.Arg239-stop in exon 4 of CYP17A1, which was confirmed by targeted sequence capture/high-throughput sequencing and Sanger sequencing technology. To the best of our knowledge, 17OHD with adrenal crisis has not been reported previously, and the reason why it arose in this patient might have been inappropriate glucocorticoid administration during the perioperative period.

Chinese abstract

17个a-羟化酶/17,20-裂解酶缺乏症(17OHD)是一种罕见的常染色体隐性疾病, 是一种先天性肾上腺增生症, 其结果是高血压、低钾血症、性幼稚症、女性原发性闭经 (46,XX), 或男性假两性畸形(46,XY)。它主要是由CYP17A1基因突变引起的, 该基因编码了类固醇生成通路中一类核心酶。然而, 由于肾上腺皮质酮水平异常升高, 这些患者很少经历肾上腺危象。在此, 我们报告一名17OHD在性腺切除术后第1天发生了肾上腺危象的患者。通过靶向序列捕获/高通量测序和Sanger测序技术确认该女患者(46,XY)的基因缺陷是CYP17A1的4号外显子c0.715C > T p.Arg239-stop。据我们所知, 先前没有关于17OHD患者肾上腺危机的相关报道, 而在这个病人中出现这种情况的原因可能是整个围手术期不适当的糖皮质激素管理。

Keywords:

• 17OHD
• gene mutation
• adrenal crisis

Acknowledgements

The authors thank all of the doctors who participated in the treatment or discussion of this case, including Prof. Weiwei Feng, Prof. Jin Zhu, Prof. Yin Zhang, and Prof. Yisong Chen.

Disclosure statement

The authors report no declarations of interest.