This is a global, multi-center, non-interventional study for patients with confirmed diagnosis of MMA due to methylmalonyl-CoA mutase
deficiency or PA.
This reaction requires the involvement of three enzymes: propionyl-CoA-carboxylase, methylmalonyl-CoA-racemase and methylmalonyl-CoA mutase
(Voet et al., 2008).
The level of methylmalonic acid in the blood and urine and the level of homocysteine in the plasma increase due to the reduced activity of the methylmalonyl-CoA mutase
enzyme and methionine synthase enzymes in vitamin B12 deficiency.12 The levels of plasma homocysteine and methylmalonic acid in the urine and the levels of total, direct, and indirect bilirubin were compared, and once again, there was no significant difference.
Keywords: Methylmalonic aciduria, Methylmalonyl-CoA mutase
deficiency, Cobalamin related remethylation disorders, Vitamin B 12 deficiency, Pakistan.
Several enzymes are involved in the incorporation of these substrates in the gluconeogenesis pathway : lactate dehydrogenase (LDH) for lactate; glycerol kinase (GK) and glycerol-3-phosphate dehydrogenase (GPD) for glycerol; and acyl-CoA synthetase short-chain family member 3 (ACSS3), propionyl-CoA carboxylase (PCC), methylmalonyl-CoA epimerase (MCEE), and methylmalonyl-CoA mutase
(MUT) for propionate.
The data, published online in the journal Cell Reports, demonstrate that intravenous administration of an mRNA therapeutic encoding for human methylmalonyl-CoA mutase
, the enzyme most frequently mutated in MMA, enabled liver expression of MUT in MMA mouse models, leading to a significant reduction in methylmalonic acid, a substantial improvement in weight gain, and the complete survival of the full cohort of treated mice versus control group.
Two enzymes are involved in this pathway, methylmalonyl-CoA mutase
and methionine synthase.
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.
MMA can build up in the bloodstreamif there is not enough vitamin [B.sub.12] in the body for an enzyme (methylmalonyl-CoA mutase
) to function properly.
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.
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.sub.12] deficiency (n = 8) were identified prospectively during routine screening or made available by various screening laboratories with informed consent or submitted for routine second-tier testing.