Analysis of clinical phenotype and genetic mutation with outcome evaluation in one family of vitamin B12-dependent methylmalonic aciduria

Objective To explore the clinical features, genetic mutation and vitamin B 12 therapeutive effectiveness in vitamin B 12- dependent methylmalonic acidemia (MMA). Methods Clinical data in a pedigree of 4 members with vitamin B 12- dependent MMA was collected. Peripheral blood samples were collected for plasma amino acids and acylcarnitines and gene muatation analysis. The therapeutic efficacy of vitamin B 12 was evaluated.  Results The initial presentations of the proband were underachievement and personality changes in 12-year old, and accompanied by visual hallucinations and weakness of lower limbs during the course of disease. The younger brother of the proband presented with bad-temper and lower acheivement. The analysis of plasma amino acid and acylcarnitine showed that proband and his younger brother's plasma propionylcarnitine and propionylcarnitine/acetylcarnitine ratio, and the level of methylmalonic acid in urine were increased significantly. Compound heterozygeous mutation of c.482G > A (p.Arg161Gln) and c.609G > A (p.Trp203X) in MMACHC gene were seen in the proband and her younger brother. Her father carried MMACHC gene missense mutation c.482G > A (p.Arg161Gln), while her mother carried MMACHC gene nonsense mutation c.609G > A (p.Trp203X). Symptoms of the proband were improved after vitamin B12 therapy.   Conclusions The late - onset vitamin B 12 -dependent MMA is caused by compound heterozygote mutation of MMACHC gene. It had good responsive to vitamin B12 therapy. Early diagnosis and timely treatment may play a critical role for the outcomes of patients with this disease. DOI: 10.3969/j.issn.1672-6731.2017.07.009