Institute of Child Health, University College London and Great Ormond Street Hospital for Children NHS Trust, London, United Kingdom.
Am J Kidney Dis. 2012 Apr;59(4):566-8. doi: 10.1053/j.ajkd.2011.09.026. Epub 2011 Dec 9.
Nephrogenic syndrome of inappropriate antidiuresis (NSIAD) is an X-linked disorder caused by activating mutations in arginine vasopressin receptor 2 (AVPR2), resulting in persistently concentrated urine. We report on a family affected by NSIAD with the known mutation R137C, an arginine to cysteine substitution at amino acid 137. The spectrum of symptoms varied markedly and ranged from infrequent voiding to incidentally noted hyponatremia to recurrent admissions with hyponatremic seizures. There was evidence for physiologic compensatory mechanisms: most affected members intuitively compensated for the concentrated urine by curtailing their fluid intake. Before the genetic diagnosis, these members had recognized each other by their infrequent voiding, which especially suited one patient, a London cab driver. Interestingly, after water deprivation, urine osmolality was significantly lower in patients compared with unaffected members, suggesting desensitization of the downstream signaling pathway with persistent AVPR2 activation. Urine osmolality was as low as 241 mOsm/kg (241 mmol/kg) in patients, which could obfuscate the diagnosis. The development of symptoms of hyponatremia was strikingly different in the 2 male patients: one patient was asymptomatic with a plasma sodium level of 120 mEq/L (120 mmol/L), whereas another experienced seizures with similar values. Investigations of such genetically defined patients show clues for the understanding of human physiology and inform diagnosis and clinical management.
肾源性尿崩症（NSIAD）是一种 X 连锁疾病，由精氨酸加压素受体 2（AVPR2）的激活突变引起，导致持续浓缩的尿液。我们报告了一个受 NSIAD 影响的家庭，其特征突变是 R137C，即精氨酸到半胱氨酸的取代，发生在氨基酸 137 处。症状谱差异显著，从不频繁排尿到偶然发现的低钠血症，再到因低钠血症性癫痫反复发作而入院。存在生理补偿机制的证据：大多数受影响的成员通过限制液体摄入，本能地补偿浓缩尿液。在基因诊断之前，这些成员通过不频繁的排尿来识别彼此，这尤其适合一位伦敦出租车司机。有趣的是，在禁水后，患者的尿液渗透压明显低于未受影响的成员，这表明下游信号通路持续激活 AVPR2 导致脱敏。患者的尿液渗透压低至 241 mOsm/kg（241 mmol/kg），这可能会使诊断变得复杂。2 名男性患者的低钠血症症状发展明显不同：一名患者无症状，血浆钠水平为 120 mEq/L（120 mmol/L），而另一名患者则出现类似值的癫痫发作。对这些基因定义患者的研究为理解人类生理学提供了线索，并为诊断和临床管理提供了信息。
