Methylmalonic aciduria is a genetically heterogeneous disorder of methylmalonate and cobalamin metabolism. Isolated methylmalonic aciduria is found in patients with mutations in the MUT gene causing partial, mut(-), or complete, mut(0), enzyme deficiency. This form is unresponsive to B12 therapy. Various forms of isolated methylmalonic aciduria also occur in a subset of patients with defects in the synthesis of the MUT coenzyme adenosylcobalamin (AdoCbl) and are classified according to complementation group: caused by mutation in the MMAA gene on chromosome 4q31 and caused by mutation in the MMAB gene.
Confirmation of a clinical diagnosis, Carrier testing in unaffected family members