Abstract: Objective To explore the clinical and genetic features in the pedigree of Cb1X type X-linked methylmalonic ciduria. Methods Clinical data of one child with X-linked methylmalonic aciduria diagnosed by blood and urine analysis ere analyzed retrospectively. Targeted next-generation sequencing has been performed to detect the mutation of methylmalonic ciduria-related genes. Results The boy started presenting with seizures and severe mental retardation at 2 months of age. At 5 onths of age, he had the manifestations of seizures, severe mental retardation, increased methylmalonic acid in urinary, increased ropionylcarnitine in blood and increased plasma homocysteine, and met the requirements for the diagnosis of methylmalonic ciduria complicated with hyperhomocysteinemia. No mutation was detected in his MMA-related autosomal genes. However, a emizygote mutation c.344C > T (p.Ala115Val) was identified in exon 3 of HCFC1 in X chromosome, which confirmed the CblX ype methylmalonic aciduria. His parents were healthy. His elder brother also manifested severe psychomotor retardation with ntractable epilepsy, and died at 6 months of age with unknown cause. His mother carried the same mutation and had slightly elevated urine methylmalonic acid and plasma total homocysteine. His father did not carry the mutation. Conclusion A pedigree of a rare Cb1X type X-linked methylmalonic acidemia is firstly diagnosed in China by the new generation sequencing technology.