Water intake disorder in a DEND syndrome afflicted patient with R50P mutation
Water intake disorder in a DEND syndrome afflicted patient with R50P mutation
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DOI：
10.1507/endocrj.ej14-0392
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发表时间：
2015-04-20
影响因子：
2
通讯作者：
Shimomura, Kenju
中科院分区：
文献类型：
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作者：
Maejima, Yuko;Hasegawa, Shinji;Shimomura, Kenju
在这项研究中，我们报告了一例发育迟缓、癫痫和新生儿糖尿病（DEND）综合征的年轻男性患者，该患者的R50P突变位于atp敏感的K+ (K- atp)通道的Kir6.2亚基。虽然大多数DEND综合征患者对磺脲类药物有耐药性，但我们的患者对磺脲类药物有反应，没有最常见的神经系统症状，如癫痫，但拒绝喝水。他的血清电解质和血浆渗透压正常，但血清加压素水平升高。为了探讨其饮水障碍的潜在机制，我们将5 μ L的340 μ M K-ATP通道开启剂二氮氧化合物或100 μ M K-ATP通道抑制剂格列本脲注射到大鼠的第三脑室，并监测其饮水情况。虽然注射格列苯脲没有效果，但注射二氮氧化物可显著增加饮水量约1.5倍，而不影响食物摄入量。这一结果表明，大脑中K-ATP通道的活性可能对水分摄入有影响。在这里，我们报告了第一例DEND综合征患者伴有饮水障碍和血清抗利尿激素水平升高，可能与K-ATP通道活性改变有关。
In this study, we present a case of developmental delay, epilepsy and neonatal diabetes (DEND) syndrome in a young male patient with the R50P mutation located in the Kir6.2 subunit of the ATP-sensitive K+ (K-ATP) channel. Whereas most patients with DEND syndrome are resistant to sulfonylurea therapy, our patient was responsive to sulfonylurea, lacked the most common neurological symptoms, such as epilepsy, but refused to drink water. His serum electrolytes and plasma osmolarity were normal but the serum vasopressin level was increased. To investigate the underlying mechanism of his water intake disorder, a 5 mu L aliquot of 340 mu M K-ATP channel opener diazoxide or 100 mu M K-ATP channel inhibitor glibenclamide was injected into the third ventricle of the rat brain, and water intake was monitored. Although the injection of glibenclamide had no effect, injection of diazoxide significantly increased water intake by about 1.5 fold without affecting food intake. This result indicates that the K-ATP channel activity in the brain may have an influence on water intake. Here, we present the first case of a DEND syndrome afflicted patient with water intake disorder and increased serum vasopressin level, possibly related to altered K-ATP channel activity.