Objective To analyze the clinical features and early diagnosis of leukoencephalopathy with vanishing white matter (VWM).Methods The clinical material and gene sequencing report of one faimily with VWM were retrospectively analyzed, and relevant literatures were reviewed.Results Patient 1, female, 4 years and 10 months old, developed the disease due to abnormal gait. Magnetic resonance imaging (MRI) of the brain showed white matter abnormality with diffuse symmetry. Gene detection revealed two missense mutations in EIF2B4 gene, both located in exon 13, respectively C. 1544 T→A and C. 1445 G→T heterozygous variation, which has not been reported. The other child was her identical sister, whose onset time, manifestations, brain MRI and gene test results were roughly the same. However, after 1-year follow-up, we found that patient 1 degraded faster.Conclusion We found two novel missense mutations C. 1544 T→A and C. 1445 G→T. Early genetic analysis is suggested to make a definite diagnosis for leukoencephalopathy with VWM.