Nephrology Division, Department of Medicine, Jacobi Medical Center, Albert Einstein College of Medicine , Bronx, NY , USA.
University Medical Center of Princeton at Plainsboro, Rutgers Robert Wood Johnson Medical School , Plainsboro, NJ , USA.
Front Med (Lausanne). 2015 Jul 7;2:43. doi: 10.3389/fmed.2015.00043. eCollection 2015.
Congenital nephrogenic diabetes insipidus (NDI) is a conformation disease resulting from protein misfolding. Ninety percent of mutations result from the inactivating mutations of the arginine vasopressin receptor 2 (AVPR2) gene transmitted in an X-linked fashion, blocking the response to vasopressin, resulting in the inability to concentrate urine. Clinical features include polyuria, polydispsia, dehydration, and hypernatremia. They are generally more severely in affected males but present variably in females due to skewed inactivation of the X chromosome. We describe a case of a 40-year-old woman with a history of Type 2 diabetes mellitus, hyperlipidemia, and obesity, who presents with debilitating polyuria since the age of 5 with no clear diagnosis. Interestingly, her son was diagnosed with NDI. Genetic testing revealed that she was heterozygous for the Val88Met mutation in the AVPR2 gene while her son was hemizygous for the same. The patient has since been successfully treated with diuretics and a low solute diet. We highlight that although X-linked NDI patients are mostly males, it should be considered in symptomatic females to prevent delays in the diagnosis. Conformational diseases such as NDI are presently the subject of research using pharmacological chaperones to restore proper receptor membrane localization and function.
先天性肾性尿崩症(NDI)是一种由蛋白质错误折叠引起的构象疾病。90%的突变是由于 X 连锁方式失活的精氨酸加压素受体 2(AVPR2)基因突变引起的,阻断了对加压素的反应,导致无法浓缩尿液。临床特征包括多尿、多饮、脱水和高钠血症。它们在受影响的男性中通常更为严重,但由于 X 染色体的偏性失活,在女性中表现出不同的程度。我们描述了一例 40 岁女性的病例,她有 2 型糖尿病、高血脂和肥胖症病史,自 5 岁起出现严重的多尿,一直未明确诊断。有趣的是,她的儿子被诊断为 NDI。基因检测显示她是 AVPR2 基因中 Val88Met 突变的杂合子,而她的儿子是相同突变的半合子。此后,该患者成功地接受了利尿剂和低溶质饮食治疗。我们强调,尽管 X 连锁 NDI 患者主要是男性,但在有症状的女性中也应考虑到这种疾病,以避免延误诊断。构象疾病,如 NDI,目前是使用药理学伴侣来恢复适当的受体膜定位和功能的研究主题。