NR0B1 基因突变致先天性肾上腺发育不全 8 例患儿的下丘脑-垂体-睾丸轴功能的纵向评估。
Longitudinal evaluation of the hypothalamic-pituitary-testicular function in 8 boys with adrenal hypoplasia congenita (AHC) due to NR0B1 mutations.
机构信息
Université Paris Descartes, Sorbonne Paris Cité, and Assistance Publique-Hôpitaux de Paris, Hôpital Bicêtre, Unité d'Endocrinologie Pédiatrique, Le Kremlin Bicêtre, France.
出版信息
PLoS One. 2012;7(6):e39828. doi: 10.1371/journal.pone.0039828. Epub 2012 Jun 27.
BACKGROUND
Boys carrying mutations in the NR0B1 gene develop adrenal hypoplasia congenita (AHC) and impaired sexual development due to the combination of hypogonadotropic hypogonadism (HH) and primary defects in spermatogenesis.
METHODS
We analysed the evolution of hypothalamic-pituitary-testicular function of 8 boys with AHC due to NR0B1 mutations. Our objective was to characterize and monitor the progressive deterioration of this function.
RESULTS
The first symptoms appeared in the neonatal period (n = 5) or between 6 months and 8.7 years (n = 3). Basal plasma adrenocorticotrophic hormone (ACTH) concentrations increased in all boys, whilst cortisol levels decreased in one case. The natremia was equal or below 134 mmol/L and kaliemia was over 5 mmol/L. All had increased plasma renin. In 3 of 4 patients diagnosed in the neonatal period and evaluated during the first year, the basal plasma gonadotropins concentrations, and their response to gonadotropin releasing hormone (GnRH) test (n = 2), and those of testosterone were normal. The plasma inhibin B levels were normal in the first year of life. With the exception of two cases these concentrations decreased to below the normal for age. Anti-Müllerian hormone concentrations were normal for age in all except one case, which had low concentrations before the initiation of testosterone treatment. In 3 of the 8 cases the gene was deleted and the remaining 5 cases carried frameshift mutations that are predicted to introduce a downstream nonsense mutation resulting in a truncated protein.
CONCLUSIONS
The decreases in testosterone and inhibin B levels indicated a progressive loss of testicular function in boys carrying NR0B1 mutations. These non-invasive examinations can help to estimate the age of the testicular degradation and cryopreservation of semen may be considered in these cases as investigational procedure with the aim of restoring fertility.
背景
携带 NR0B1 基因突变的男孩会出现先天性肾上腺发育不全（AHC）和性发育障碍，这是由于促性腺激素低下性性腺功能减退症（HH）和原发性生精障碍共同作用的结果。
方法
我们分析了 8 名因 NR0B1 突变导致 AHC 的男孩的下丘脑-垂体-睾丸功能演变。我们的目的是描述和监测这种功能的逐渐恶化。
结果
首发症状出现在新生儿期（n = 5）或 6 个月至 8.7 岁（n = 3）。所有男孩的基础血浆促肾上腺皮质激素（ACTH）浓度均升高，而 1 例皮质醇水平降低。血钠等于或低于 134mmol/L，血钾高于 5mmol/L。所有患者的血浆肾素均增加。在 4 名新生儿期诊断并在第一年评估的患者中，有 3 名患者的基础血浆促性腺激素浓度及其对促性腺激素释放激素（GnRH）测试（n = 2）的反应以及睾酮的浓度正常。在生命的第一年，血浆抑制素 B 水平正常。除 2 例外，这些浓度均降至年龄正常以下。除 1 例外，所有患者的抗苗勒管激素浓度均在年龄正常范围内，该患者在开始睾酮治疗前浓度较低。在 8 例中，有 3 例基因缺失，其余 5 例携带移码突变，预计会导致下游无意义突变，从而产生截短蛋白。
结论
睾酮和抑制素 B 水平的降低表明携带 NR0B1 基因突变的男孩睾丸功能逐渐丧失。这些非侵入性检查有助于估计睾丸退化的年龄，在这些情况下，可以考虑进行精液冷冻保存作为研究性程序，以恢复生育能力。
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