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.
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.
The largest group of defects associated with C3-carnitine elevation involves the downstream enzyme methylmalonyl-CoA mutase
Classical MMA results from deficiency of methylmalonyl-CoA mutase
, a cobalamin- (vitamin [B.
MMA results from deficiency of the immediately downstream enzyme methylmalonyl-CoA mutase
, which catalyzes the vitamin [B.
Alternatively, female sex hormones may cause intracellular cobalamin redistribution favoring supply of cobalamin as a cofactor for methionine synthase at the expense of the methylmalonyl-CoA mutase
Its two metabolically active forms, methyl-cobalamin and 5-deoxyadenosylcobalamin, are coenzymes in the reactions catalyzed, respectively, by methionine synthase and methylmalonyl-CoA mutase
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.
It is possible that the two enzymes that require cobalamin, methionine synthase (which requires methyl-cobalamin) and methylmalonyl-CoA mutase
(which requires adenosyl-cobalamin), behave differently in their response to the declining availability of cobalamin.