Methylmalonic acidemia (MMA) is usually caused by a deficiency of the enzyme methylmalonyl-CoA mutase (MCM), a defect in the transport or synthesis of its cofactor, adenosyl-cobalamin (cblA, cblB, cblC, cblF, cblD, and cblX), or deficiency of the enzyme methylmalonyl-CoA epimerase. A comprehensive diagnostic approach involves investigations of metabolites with tandem mass spectrometry, organic acid analysis with gas chromatography, enzymatic studies with fibroblast cell culture, and finally, mutation analysis. With biochemical techniques and enzymatic assay the reliable characterization of patients with isolated MMA for mutation analysis can be achieved. Reliable classification of these patients is essential for ongoing and prospective studies on treatments, outcomes, and prenatal diagnoses. This article reviews the diagnostic techniques used to characterize patients with MMA.
Keywords: Diagnostic techniques; Enzyme assay; Methylmalonic acidemia; Mutation analysis; Organic acid analysis; Tandem mass spectrometry.