先天型白质消融性白质脑病1例及其基因突变分析

The clinical and genetic features of a case with antenatal form of leukoencephalopathy with vanishing white matter disease

目的探讨先天型白质消融性白质脑病(VWM)的临床及基因特点。方法回顾性分析1例先天型VWM患儿的临床资料及基因检测结果。结果患儿,男,3月龄,因间断抽搐2个月就诊,出生体质量1 900 g,生后有窒息史;发育落后,不能注视、追视,不能逗笑、抬头,下肢肌张力升高,双眼白内障。头颅CT及MRI可见大脑白质弥漫性异常,与脑脊液信号相同。基因检测结果显示,EIF2B5基因存在错义突变(c.1016G>A)和移码突变(c.1809delC),为复合杂合突变,其父母均为杂合子。结论 VWM是遗传性白质脑病之一,先天型极为罕见,诊断需根据临床表现及EIF2B基因分析。移码突变位点c.1809del C国际上尚未见报道。

Objective To explore the clinical features and gene mutations of antenatal form leukoencephalopathy with vanishing white matter disease （VWM）. Methods The clinical data and genetic test results in a patient with antenatal form of VWM were retrospectively analyzed. Results A three months old patient was admitted to our hospital with intermittent convulsions commenced from the first month after birth. The baby had low birth weight （1900g） and asphyxia at birth. Developmental retardation and cataracts in both eyes were found on physical examination, and the patient couldn＇t stare, gaze-following, be amused and raise his head. In addition, he showed hypermyotonia of both lower extremities. Diffused and symmetrical abnormal signals same as that of the cerebrospinal fluid in the cerebral white matter were observed by brain CT and MRI scanning, and the lesions were gradually enlarged. Moreover, a missense mutation （c. 1016G〉A） and a frameshift mutation （c. 1809delC） in EIF2B5 gene inherited from his parent were detected by DNA sequencing. Conclusions VWM is one of the most prevalently inherited childhood white matter disorders, but the case of antenatal form is very rare. The diagnosis should be based on clinical manifestations and EIF2B genetic analysis. To our knowledge, the frameshift mutation c. 1809delC has never been reported to date.