We report the lack of megaloblastic anaemia in a patient with severe methionine synthase deficiency who is also homozygous for C677T in MTHFR, hypothesize that the MTHFR polymorphism protects the patient against anaemia and speculate that homozygosity for MTHFR C677T could cause the dissociation between haematological and neurological disease seen in some patients with vitamin B12 deficiency.
In contrast, methionine formation was reduced in cells from patients with methylenetetrahydrofolate reductase (MR) deficiency (MR mutant, n = 11, 0.05-0.44), combined methylmalonic aciduria/homocystinuria [cobalamin(cbl)C/D mutant, n = 12, 0.014-0.13), and methionine synthase deficiency (MS mutant, n = 3, 0.04-0.23).