Objective The purpose of this study was to research the molecular genetic mechanism of alpha-mannosidosis, to reveal the relationship between the genotype and phenotype, and to provide a prerequisite for prenatal gene diagnosis in future.Methods The proband was preliminarily diagnosed by clinical symptom and imaging examination.A definite diagnosis was performed by detecting the alpha-mannosidase activity and directly sequencing the gDNA and cDNA of MAN2B 1 gene.Finally, DHPLC, conservative analysis and protein secondary structure prediction were used to identify the pathogenicity of this novel mutation.Results The patient has compound heterozygous mutations of c.856G>A (novel) and c.788C>T in MAN2B1 gene.The probands father and mother are heterozygous with the c.788C>T and c.856 G>A mutation respectively.All the identification results for the novel mutation are consistent with expected ones.Conclusions The c.856G>A was a novel disease-causing mutation, which was the main cause of the disease suffered by the child in this family.This research was the first gene diagnosis of Chinese patient with alpha-mannosidosis.