Abstract Objective The research aims to investigate the clinical characteristics and NAXE genetic pathogenicity of early-onset progressive encephalopathy with brain edema and / or brain white matter disease (PEBEL1) caused by rare NAXE (or APOA1BP) related gene defects. Methods The clinical characteristics and exome sequencing (WES) of a pediatric patient with unexplained walking disorder were analyzed; Results The patient was a girl aged 2 years and 10 months. She was hospitalized due to "walking disorder for more than 40 days". Her clinical manifestations were ataxia, motor function regression, hypotonia, and eyelid ptosis. Within one month after she was in hospital, her symptoms included sighing breathing, respiratory failure, cerebellar edema and brain hernia, and finally she died. Changes were found in cranial imaging, including cerebellar edema accompanied by symmetrical myelopathy. Through WES, we detected NAXE two compound heterozygous variation( NM 144772.3: c.733A>C , c.370G>T and c.733A>C, c.304_c.305insA) in germline gene. Sanger sequencing confirmed that the compound heterozygous mutations were derived from the parents of the two probands, respectively. The results of bioinformatics analysis suggested that the mutation was pathogenic. Conclusion This case is the first report of NAXE related PEBEL1 with severe clinical phenotype in mainland China. The disease is quick in progression with unfavorable prognosis. Gene detection is the only diagnostic method. The c.370G>T and c.304_c.305insA mutations discovered in this paper has enriched the pathogenic variation spectrum of NAXE.