MMA is a compound that can build up in the bloodstream if there isn't enough vitamin B12 in the body for an enzyme, methylmalonyl-CoA
mutase, to function properly.
Samples obtained from the original NBS specimens of confirmed cases with [beta]-cystathionine synthase deficiency (n = 4), propionyl-CoA carboxylase deficiency (n = 2), methylmalonyl-CoA mutase deficiency (n = 4), Cbl C deficiency (n = 7), various remethylation disorders [methylenetetrahydrofolate reductase (MTHFR), n = 3; Cbl G, n = 3; Cbl D variant 1, n = 1], and maternal vitamin [B.
Since 2005, we have prospectively identified 2 infants with [beta]-cystathionine synthase deficiency, 1 with MTHFR deficiency, 1 with Cbl G deficiency, 2 with methylmalonyl-CoA mutase deficiency, and 7 with Cbl C deficiency, as well as 8 mothers with vitamin [B.
D-methylmalonyl CoA is isomerized to L-methylmalonyl CoA via methylmalonyl-CoA
Methylmalonic Acidemias [Adenosylcobalamin Synthesis Defects (CblA and CblB) and Methylmalonyl-CoA
Mutase Deficiencies (mut- and mut+)]--An enzymatic defect in the oxidation of amino acids is the cause of these conditions, with an incidence of 1 in 50,000 to 1 in 100,000 live births.
12] is an essential cofactor for L-methylmalonyl-CoA
mutase, which converts methylmalonyl-CoA
to succinyl-CoA (1).
Normally propionyl-CoA is metabolized to methylmalonyl-CoA
by the action of propionyl-CoA carboxylase (PCC), but if the metabolite is in excess the propionyl species is released from the mitochondrion after conversion by carnitine palmitoyl transferase II to the corresponding acylcarnitine (Fig.
Classical MMA results from deficiency of methylmalonyl-CoA
mutase, a cobalamin- (vitamin [B.
PA results from a defect in the enzyme propionyl-CoA carboxylase, which catalyzes the biotin-dependent conversion of propionyl-CoA to methylmalonyl-CoA
An example is increased propionylcarnitine (C3-acylcarnitine), a finding that requires differentiation of several disorders: propionyl-CoA carboxylase deficiency, methylmalonyl-CoA
mutase deficiency, several cobalamin disorders, and even dietary deficiency of vitamin B1, This requires the expertise of clinical and biochemical geneticists and a variety of diagnostic tests.
PA is caused by deficiency of propionyl-CoA carboxylase, whereas MMA results from deficiency of either methylmalonyl-CoA
mutase or defects in the production of adenosylcobalamin.
Cobalamin is also an essential cofactor in the enzymatic conversion of methylmalonyl-CoA
to succinyl-CoA by the enzyme L-methylmalonyl-CoA
mutase (13); cobalamin deficiency therefore leads to an increased serum concentration of methylmalonic acid (12,14).