MTR and Decreased circulating vitamin B12 concentration: As an essential cofactor for the intracellular enzymes cytoplasmatic methionine synthase and mitochondrial methylmalonyl-CoA mutase [18], cobalamin deficiency can lead to functional folate deficiency and increased serum concentrations of homocysteine (HCY), both due to methionine synthase inactivation, and accumulation of methylmalonic acid (MMA) due to reduced methylmalonyl CoA mutase activity [19–21].