Genotyping is definitive for the diagnosis of mitochondrial DNA depletion syndrome (MDS).Here we report a Chinese infant of MDS with two heterozygous mutations in the DGUOK gene.Recurrent hypoglycemia attacks since first week of life, progressive cholestatic liver dysfunction and later develop mild hypotonia were noticed.A liver biopsy specimen showed serious intrahepatic cholestasis with extensive fibrosis.Sequence analysis of mtDNA isolated from blood revealed c.679G>A (p.E227K) mutation in exon 5 and a novel mutation, c.630dupG (p.E210fs) mutation in exon 5, that lead to truncated proteins.The same mutation c.630dupG was present in heterozygous form in his mother.Organ transplant may be a reasonable option for patient with organ-specific mtDNA depletion, However, it remains to be seen whether this patient will develop mtDNA depletion in other organs later in life.Effective treatment need more research.