Abstract: Objective To explore the genotype and phenotype of two patients with white matter melting leukoencephalopathy (VWM). Methods Clinical data of two children with VWM diagnosed through genetic test were retrospectively analyzed, with a review of  relevant literature. Results Onset age of the two patients were 8 months and 2 years old, respectively. Their psychomotor development were previously normal. They were with poor response after acute fever, and cognition and motor function were progressively regressed. Their cerebrospinal fluid examination was normal. Brain MRI showed symmetry abnormal signal in the hemispheres brain white matter. Genetictest found compound heterogeous mutations in EIF2B5gene in the both cases, and a c. 911_913del mutation caused deletion of 305th amino acid. Conclusions VWM was characterized by previously normal mental and motor development, and later progressive regression  after fever, and with poor prognosis. Brain MRI manifestation of the disease was widely symmetry brain white matter involvement, and gradually evolved into the same signal of cerebrospinal fluid. Mutations found in EIF2B can determine the diagnosis of  VWM.