Komaki Ryouhei, Ueda Takehiro, Tsuji Yukio, Miyawaki Toko, Kusuhara Sentaro, Hara Shigeo, Toda Tatsushi
Division of Neurology, Kobe University Graduate School of Medicine.
Department of Neurology, Kita-Harima Medical Center.
Rinsho Shinkeigaku. 2018 Feb 28;58(2):111-117. doi: 10.5692/clinicalneurol.cn-001096. Epub 2018 Jan 31.
A 40-year-old woman with renal dysfunction for 2 years was admitted to our hospital suffering from a headache. Family history revealed that her mother had a headache, renal dysfunction, and brain infarction in younger age. She had a retinal hemorrhage, a retinal atrophy, pitting edema in her lower extremities. Her neurological findings were unremarkable. Brain imaging showed multiple white matter lesions accompanied with calcifications and slightly enhancement. Kidney biopsy showed the thrombotic microangiopathy, Gene analysis demonstrated a causative mutation in three-prime repair exonuclease-1 (TREX1) gene, c.703_704insG (p.Val235GlyfsX6), thereby we diagnosed her as retinal vasculopathy with cerebral leukoencephalopathy (RVCL). RVCL is an autosomal dominant condition caused by C-terminal frame-shift mutation in TREX1. TREX1 protein is a major 3' to 5' DNA exonuclease, which are important in DNA repair. While TREX1 mutations identified in Aicardi-Goutieres syndrome patients lead to a reduction of enzyme activity, it is suggested that mutations in RVCL alter an intracellular location of TREX1 protein. There are no treatments based evidences in RVCL. We administered cilostazol to protect endothelial function, and her brain lesions and renal function have not become worse for 10 months after. It is necessary to consider RVCL associated with TREX1 mutation if a patient has retinal lesions, white matter lesions accompanied with calcifications, and multiple organ dysfunction.
一名肾功能不全2年的40岁女性因头痛入院。家族史显示,她的母亲在年轻时患有头痛、肾功能不全和脑梗死。她有视网膜出血、视网膜萎缩、下肢凹陷性水肿。神经系统检查结果无异常。脑部影像学显示多个白质病变伴有钙化和轻度强化。肾活检显示血栓性微血管病,基因分析显示三磷酸修复外切核酸酶-1(TREX1)基因存在致病突变,c.703_704insG(p.Val235GlyfsX6),因此我们将她诊断为伴有脑白质脑病的视网膜血管病变(RVCL)。RVCL是一种由TREX1基因C端移码突变引起的常染色体显性疾病。TREX1蛋白是一种主要的3'至5' DNA外切核酸酶,在DNA修复中起重要作用。虽然在Aicardi-Goutieres综合征患者中鉴定出的TREX1突变导致酶活性降低,但有人认为RVCL中的突变改变了TREX1蛋白的细胞内定位。RVCL尚无基于治疗的证据。我们给予西洛他唑以保护内皮功能,10个月后她的脑部病变和肾功能未恶化。如果患者有视网膜病变、伴有钙化的白质病变和多器官功能障碍,则有必要考虑与TREX1突变相关的RVCL。