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

Abstract

Objective To explore the clinical features, genetic mutation and vitamin B12 therapeutive effectiveness in vitamin B12-dependent methylmalonic acidemia (MMA). Methods Clinical data in a pedigree of 4 members with vitamin B12-dependent MMA was collected. Peripheral blood samples were collected for plasma amino acids and acylcarnitines and gene muatation analysis. The therapeutic efficacy of vitamin B12 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 B12 -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

Keywords

• Methylmalonic acid
• Metabolism, inborn errors
• Vitamin B12
• Phenotype
• Genes
• Mutation
• Pedigree