Kanda Shoichiro, Morisada Naoya, Kaneko Naoto, Yabuuchi Tomoo, Nawashiro Yuri, Tada Norimasa, Nishiyama Kei, Miyai Takayuki, Sugawara Noriko, Ishizuka Kiyonobu, Chikamoto Hiroko, Akioka Yuko, Iijima Kazumoto, Hattori Motoshi
Department of Pediatric Nephrology, Tokyo Women's Medical University School of Medicine, Tokyo, Japan.
Department of Pediatrics, Kobe University Graduate School of Medicine, Kobe, Japan.
Pediatr Transplant. 2016 May;20(3):467-71. doi: 10.1111/petr.12690. Epub 2016 Feb 21.
CAKUT are the most frequent causes of ESRD in children. Mutations in the gene encoding HNF1B, a transcription factor involved in organ development and maintenance, cause a multisystem disorder that includes CAKUT, diabetes, and liver dysfunction. Here, we describe the case of a patient with renal hypodysplasia who developed NODAT presenting with liver dysfunction. The NODAT was initially thought to be steroid and FK related. However, based on the patient's clinical features, including renal hypodysplasia and recurrent elevations of transaminase, screening for an HNF1B mutation was performed. Direct sequencing identified a novel splicing mutation of HNF1B, designated c.344 + 2T>C. Because CAKUT is the leading cause of ESRD in children and HNF1B mutations can cause both renal hypodysplasia and diabetes, HNF1B mutations may account for a portion of the cases of NODAT in pediatric patients who have undergone kidney transplantation. NODAT is a serious and major complication of solid organ transplantation and is associated with reduced graft survival. Therefore, for the appropriate management of kidney transplantation, screening for HNF1B mutations should be considered in pediatric patients with transplants caused by CAKUT who develop NODAT and show extra-renal symptoms.
先天性肾脏和尿路畸形（CAKUT）是儿童终末期肾病（ESRD）最常见的病因。编码肝细胞核因子1β（HNF1B）的基因突变会导致一种多系统疾病，该转录因子参与器官的发育和维持，这种多系统疾病包括CAKUT、糖尿病和肝功能障碍。在此，我们描述了一例患有肾发育不全的患者，该患者发生了新发糖尿病并伴有肝功能障碍。最初认为该新发糖尿病与类固醇和他克莫司有关。然而，基于患者的临床特征，包括肾发育不全和转氨酶反复升高，对HNF1B突变进行了筛查。直接测序鉴定出一种新的HNF1B剪接突变，命名为c.344 + 2T>C。由于CAKUT是儿童ESRD的主要病因，且HNF1B突变可导致肾发育不全和糖尿病，HNF1B突变可能在接受肾移植的儿科患者新发糖尿病的部分病例中起作用。新发糖尿病是实体器官移植的一种严重且主要的并发症，与移植肾存活率降低相关。因此，为了对肾移植进行适当管理，对于因CAKUT接受移植且发生新发糖尿病并出现肾外症状的儿科患者应考虑筛查HNF1B突变。
