A rare enzymatic defect, true isolated 17,20-lyase deficiency leading to endocrine disorders and infertility: case report

Abstract

The cytochrome P450 17A1 catalyzes the formation of 17-hydroxysteroids and 17-ketosteroid. Most defects in CYP17A1 impair both enzymatic activities and cause a combined 17α-hydroxylase/17,20-lyase deficiency, which impairs hormone production (cortisol and sex steroids), sexual development, and puberty. Isolated 17,20-lyase deficiency is usually defined by evidently normal activity of 17α-hydroxylase with a dramatic decline of 17,20-lyase activity or complete inactivity. The changes in enzyme activity lead to a lack in the production of sex steroids with normal levels of glucocorticoid and mineralocorticoid hormones. A 24-years-old married woman, as a product of a consanguineous marriage, presented with infertility and a background marked by primary amenorrhea. Laboratory data showed low normal serum cortisol levels and low levels of 17-hydroxyprogesterone. Also, her adrenal androgens were low but estradiol was normal. The chromosomal investigation uncovered a male karyotype of 46, XY. These clinical and laboratory evidence confirm the determination of an isolated 17,20-lyase deficiency in a genotypic male.

摘要：

细胞色素P450 17A1催化17-羟皮质类固醇和17-酮类固醇的形成, CYP17A1中的大多数缺陷都会损害酶的活性并导致17a羟化酶/17,20-裂解酶的缺乏, 从而影响激素的产生（皮质醇和性类固醇）、性发育和青春期发育。单独的17,20-裂解酶缺陷的定义为17a-羟化酶活性明显正常, 17,20-裂解酶活性显著下降或完全失活。酶活性的变化导致性类固醇激素正常, 但缺乏糖皮质激素和盐皮质激素。一位24岁的已婚女性, 其父母是近亲结婚, 她的临床特点是不育和原发性闭经。实验室数据显示她的血清皮质醇水平和17-羟孕酮水平低。同时, 她的肾上腺雄激素水平较低, 而雌二醇水平正常。染色体检测结果是：46, XY的男性核型。这些临床和实验室证据证实了患者是一个基因型男性患者, 她的17, 20-裂解酶缺失。

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:

• Infertility
• adrenal hyperplasia
• isolated 17,20-lyase deficiency
• amenorrhea
• gonads

Acknowledgements

The authors thank the patient for participating in this study and all clinical staff at Al-Zahra Hospital (Department of Endocrinology, Metabolism and Internal Diseases, Isfahan University of Medical Sciences) for their excellent technical assistance. The authors wish to thank prof. Mansoor Salehi (Professor of Molecular Genetics, Department of Genetics and Molecular Biology, School of Medicine, Isfahan University of Medical Sciences) for providing valuable expert advice in this study.

Compliance with ethical standards

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. Isfahan The Endocrine and Metabolism Research Center of Isfahan University of Medical Sciences approved the study.

Informed consent

Informed consent was obtained from all individual participants included in the study.

Disclosure statement

The authors declare that they have no conflict of interest.