白质消融性白质脑病1例临床特征与基因类型分析

Genotype-phenotype analysis in a patient of leukoencephalopathy with vanishing white matter

目的探讨白质消融性白质脑病的临床特点及早期诊断。方法回顾分析1例白质消融性白质脑病患儿的临床资料,并复习相关文献。结果患儿,女,1岁4个月,发热后出现运动、智力急剧倒退。在发病1周内逐渐出现吞咽困难、构音障碍、不能行走及进入昏迷。头颅磁共振成像示白质异常,且弥漫对称,最后出现和脑脊液相似的信号。基因检测发现患儿EIF2B5基因存在2个错义突变,分别位于外显子3和7的C.407 G>A(p.R 136H)和C.944G>A(p.R 315H)杂合变异,国内外均未报道,为新发现的基因变异。结合国外临床诊断标准及基因分析结果确诊为白质消融性白质脑病。因无有效的治疗手段,仅抗感染及对症治疗后患儿进入昏迷。结论发现2个新的EIF2B5基因错义突变,基因分析有助明确诊断白质消融性白质脑病。

Objective To analyze the clinical features and early diagnosis of leukoencephalopathy with vanishing white matter(VWM).Method The clinical data and gene sequencing report of one child with VWM were retrospectively analyzed,and relevant literatures at home and abroad were reviewed.Result The child,a 16-month-old girl,had normal movement and intelligence before onset.The motor development and intelligence were rapidly regressed after fever.Dysphagia,dysarthria,inability to walk and coma gradually appeared within one week.Cephalic MRI suggests an abnormal white matter,diffused symmetry,and a signal similar to that of cerebrospinal fluid.The results of genetic sequencing identified two missense mutations:c.407G>A(p.R136H)mutation on exon 3 and c.994G>A(p.R315H)mutation on exon 7 in EIF2B5 gene.VWM has poor prognosis and has no effective treatment,and coma was present after anti-infection and supportive treatment.Conclusion Two missense mutations:c.407G>A(p.R136H)mutation and c.994G>A(p.R315H)mutation are novel.Early genetic analysis is suggested to make a definite diagnosis for leukoencephalopathy with VWM.