Novel Mutations Found in Two Genes of Thai Patients with Isolated Methylmalonic Acidemia

Molecular genetic analysis of three patients diagnosed with isolated methylmalonic acidemia (MMA) revealed that one was mut ⁰ MMA, with a mutation in the MUT gene encoding the l-methylmalonyl-CoA mutase (MCM), and two were cblB MMA, with mutations in the MMAB gene required for synthesizing the deoxyadenosylcobalamin cofactor of MCM. The mut ⁰ patient was homozygous for a novel nonsense mutation in MUT, p.R31X (c.167C [rightward arrow] T), and heterozygous for three previously described polymorphisms, p.K212K (c.712A [rightward arrow] G), p.H532R (c.1671A [rightward arrow] G), and p.V671I (c.2087G [rightward arrow] A). The new MMAB mutation, p.E152X (c.454G [rightward arrow] T), was found to be homozygous in one cblB patient and heterozygous in the other patient, who also had four intron polymorphisms in this gene.