Western blot analysis revealed reduced MUT protein for all 34 cell lines (27 mut(0) , seven mut(-) ) tested, suggesting protein instability as a major mechanism of deficiency in mut-type MMA.
We report this novel mutation, including its clinical and biochemical features and genetic defects, in the MUT gene of three patients affected with isolated MMA.
The results show that propionate metabolism and methylmalonyl-CoA mutase (MCM) activity are intact in primary T cells, EBV-B cells, and CD34+ haematopoietic stem cell-derived granulocytes, whereas they are defective in those from a mut MMA child.
Mutations in the MUT gene, which encodes the mitochondrial enzyme methylmalonyl-CoA mutase, are responsible for the mut form of methylmalonic aciduria (MMA).
Mutations in the MUT locus encoding for the methylmalonyl-CoA mutase (MCM) apoenzyme are responsible for the mut forms of methylmalonic acidemia (MMA).
Mutase-deficient (MUT) methylmalonic aciduria (MMA) is an autosomal recessive inborn error of organic acid metabolism, resulting from a functional defect in the nuclear encoded mitochondrial enzyme methylmalonyl-CoA mutase (MCM) (EC.5.4.99.2).
Methylmalonic acidemia (MMA) is an autosomal recessive inherited disorder caused by complete or partial deficiency of the enzyme methylmalonyl-CoA mutase (mut0 enzymatic subtype or mut- enzymatic subtype, respectively); a defect in the transport or synthesis of its cofactor, adenosyl-cobalamin (cblA, cblB, or cblD-MMA); or deficiency of the enzyme methylmalonyl-CoA epimerase.
Methylmalonic acidemia (MMA) is a common organic acidemia, mainly due to methylmalonyl-CoA mutase (MCM) or its coenzyme cobalamin (VitB12) metabolic disorders.
Methylmalonic acidemia (MMA) can be caused by mutations in the gene coding for the methylmalonyl CoA mutase (MCM) apoenzyme or by mutations in genes required for provision of its adenosylcobalamin cofactor.
Methylmalonic acidemia (MMA) is caused by the deficient activity of l-methylmalonyl-CoA mutase, which is a vitamin B(12) (or cobalamin, Cbl)-dependent enzyme.
Methylmalonic acidaemia (MMA) is a genetic disorder caused by defects in methylmalonyl-CoA mutase or in any of the different proteins involved in the synthesis of adenosylcobalamin.
Isolated methylmalonic acidemia (MMA) is a genetically heterogeneous organic acid disorder caused by either deficiency of the enzyme methylmalonyl-CoA mutase (MCM), or a defect in the biosynthesis of its cofactor, adenosyl-cobalamin (AdoCbl).
In order to accurately model the human MMA disorder we introduced this mutation onto the human methylmalonyl-CoA mutase locus of a bacterial artificial chromosome.
Genetic and biochemical prenatal diagnosis was performed at 11 weeks of gestation in a family with a proband affected by mut methylmalonic aciduria (MMA) and homozygotes for the MUT gene c.643G>A (p.Gly215Ser) mutation.