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首页> 美国卫生研究院文献>Journal of the Endocrine Society >SAT-010 Non-Classic POR Deficiency as a Cause of Menstrual Disorders Infertility
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SAT-010 Non-Classic POR Deficiency as a Cause of Menstrual Disorders Infertility

机译：SAT-010非经典的POR缺乏作为月经性疾病和不孕症的原因

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P450 oxidoreductase deficiency (PORD) is an autosomal recessive disease caused by bi-allelic mutations of the POR gene. It is responsible for decreased activity of several P450 enzymes including CYP21A2, CYP17A1 and CYP19A1 that are involved in adrenal and/or gonadal steroidogenesis. PORD is typically diagnosed in neonates and children with ambiguous genitalia and/or skeletal abnormalities. Adult-onset PORD has been very seldom reported and little is known about the optimal way to investigate and treat such patients. In this series, we report five women aged 19-38 years, who were referred for unexplained oligo-/amenorrhea and/or infertility. Genetic testing excluded 21-hydroxylase deficiency (21OH-D), initially suspected due to increased 17-hydroxyprogesterone (17-OHP) levels. Extensive phenotyping, steroid profile by mass spectrometry, pelvic imaging and next-generation sequencing of 84 genes involved in gonadal and adrenal disorders were performed in all patients. In Vitro Fertilization (IVF) followed by frozen embryo transfer under glucocorticoid suppression therapy was performed in two patients. All patients had oligomenorrhea or amenorrhea. None had hyperandrogenism. Low-normal serum estradiol (E2) and testosterone levels contrasted with chronically increased serum progesterone (P) and 17-OHP levels, which further increased after ACTH administration. Despite excessive P, 17OH-P and 21-deoxycortisol rises after ACTH stimulation suggesting non-classic 21-hydroxylase deficiency, CYP21A2 sequencing did not support this hypothesis. Basal serum cortisol levels were low to normal, with inadequate response to ACTH in some women, suggesting partial adrenal insufficiency. Pelvic imaging revealed bilateral ovarian macrocysts in all women. All patients were found to harbor rare bi-allelic POR mutations classified as pathogenic according to American College of Medical Genetics standards. IVF was performed in two women after retrieval of a normal oocyte number despite very low E2 levels during controlled ovarian hyperstimulation. Frozen embryo transfer under glucorticoid suppression therapy led to successful pregnancies. These observations suggest that diagnosis of PORD must be considered in infertile women with chronically elevated P and 17OH-P levels and ovarian macrocysts. Differentiation of this entity from non-classic 21-hydroxylase deficiency is important, as the multiple enzyme deficiency requires a specific management. Successful fertility induction is possible by IVF, providing that P levels be sufficiently suppressed by glucocorticoid therapy prior to implantation.
机译：P450氧化还原酶缺乏（POR）是由POR基因的双位等位基因突变引起的常染色体隐性疾病。它负责降低几种p450酶的活性，包括参与肾上腺和/或性腺类甾体化的CYP21A2，CYP17A1和CYP19A1。 PORD通常被诊断为具有暧昧生殖器和/或骨骼异常的新生儿和儿童。成年人的PORE非常简称，众所周知，关于调查和治疗此类患者的最佳方式。在本系列中，我们报告了五名19-38岁的女性，他被提及了未解释的寡核和闭经和/或不孕症。基因检测排除了21-羟化酶缺乏（21OH-D），最初由于17-羟基酯（17-OHP）水平增加而怀疑。在所有患者中，在所有患者中进行了广泛的表型，通过质谱法，通过质谱，盆腔成像和参与的84个基因的下一代测序。体外施肥（IVF），然后在两名患者中进行糖皮质激素抑制治疗下的冷冻胚胎转移。所有患者均有少霉菌或闭经。没有高血糖。低正常的血清雌二醇（E2）和睾酮水平与慢性血清孕酮（P）和17-OHP水平相比形成对比，其在施用后进一步增加。尽管P，17OH-P和21-脱氧硅藻精升高后acth刺激呈非典型的21-羟化酶缺乏，CYP21A2测序不支持该假设。基础血清皮质醇水平较低至正常，对某些女性的acth反应不足，表明部分肾上腺功能不全。骨盆成像显示所有女性的双侧卵巢癌。根据美国医学遗传学标准，均发现所有患者含有稀有的双等位基因POR突变，归类为致病性。尽管在受控卵巢过度刺激期间的E2水平非常低，但在正常卵母细胞数中检索后，在两名女性中进行了IVF。葡萄糖皮下抑制治疗下的冷冻胚胎转移导致了成功的怀孕。这些观察结果表明，在慢性升高的P和17OH-P水平和卵巢宏观上，必须考虑对POR的诊断。随着多种酶缺乏需要特异性管理，这种实体与非经典的21-羟化酶缺乏的分化很重要。 IVF可以实现成功的生育能力，从而通过在植入前通过糖皮质激素治疗充分抑制p水平。

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