Methylmalonyl CoA mutase catalyzes the isomerization of methylmalonyl CoA into succinyl-CoA. The coenzyme adenosylcobalamin (AdoCbl) is also required for this reaction. Mutations in the MUT gene cause mutase-deficient MMA. MUT is a nuclear gene (6q21) that codes for the mitochondrial enzyme, methylmalonyl CoA mutase. Based on enzymatic activity in cultured fibroblasts, two phenotypic variants of mutase deficient MMA have been defined. The mut0 phenotype has no detectable enzymatic activity and is associated with severe symptoms in patients. The mut- phenotype has residual activity that is increased by supplementation of hydroxycobalamin and is associated with variable severity.
Apart from primary deficiency of mutase activity, insufficient metabolism of cobalamin can also result in deficient mutase activity. MMAA and MMAB genes are involved in the adenosylcobalamin metabolism (associated with the cblA and cblB complementation groups of MMA, respectively). (Refer to MMAA and MMAB gene sequencing for more information.)
For patients with mutations not identified by full gene sequencing, a separate deletion/duplication assay is available using a targeted CGH array NK.
- Clinical symptoms of possible non-B12 responsive MMA
- Follow up to abnormal newborn screening results suggestive of MMA
- Clinical symptoms of MMA, with negative MMAA/MMAB gene sequencing
- Family members who are at risk to be carriers of MMA, when the proband is unavailable for testing.
Submit only 1 of the following specimen types
Preferred specimen type: Whole Blood
Type: Whole Blood
Specimen Requirements:In EDTA (purple top) tube:
Infants (<2 years): 2-3 ml
Children (>2 years): 3-5 ml
Older Children & Adults: 5-10 ml
Specimen Collection and Shipping: Refrigerate until time of shipment. Ship sample within 5 days of collection at room temperature with overnight delivery.
Specimen Requirements:OrageneTM Saliva Collection kit (available through EGL) used according to manufacturer instructions.
Specimen Collection and Shipping: Store sample at room temperature. Ship sample within 5 days of collection at room temperature with overnight delivery.
- Organic Acid Analysis (OA) is used in the diagnosis of patients with MMA
- Methylmalonic Acid Quantitation (MQ) is used in diagnosis and follow up of propionate and methylmalonic disorders, as well as defects of cobalamin synthesis; it can also detect acquired cobalamin, and/or folate deficiency
- MMAA/MMAB (MU) Gene Sequencing may be considered in patients with a biochemical diagnosis of MMA but with normal MUT gene sequencing
- Custom Diagnostic Mutation Analysis (KM) is available to family members if mutations are identified by sequencing.
- Prenatal testing is available to couples who are confirmed carriers of gene mutations. Please contact the laboratory genetic counselor prior to sending a specimen.