METHIONINE SYNTHASE DEFICIENCY WITHOUT MEGALOBLASTIC-ANEMIA

We report findings on a child presenting with neonatal homocystinuria, hypomethioninaemia and severe neurological symptoms, including develo pmental delay and seizures. Methylmalonic aciduria was not present. Th e activity of methionine synthase in fibroblasts was severely deficien t and formation of methylcobalamin from Co-57 labelled cyanocobalamin was very low. The patients cells complemented with those of a cblE pat ient but not with those of two cblG patients. No biochemical or clinic al response to injections of hydroxycobalamin was found. Both off trea tment and on betaine and methionine supplementation the patient, at ag e 8 years, has not developed megaloblastic anaemia. In addition, the p atient is homozygous for the C677T polymorphism in the 5,10 methylenet etrahydrofolate reductase (MTHFR) gene and the concomitant existence o f this mutation with the methionine synthase defect may prevent folate <<trapping>> and thus anaemia. Conclusion We report the lack of megal oblastic anaemia in a patient with severe methionine synthase deficien cy who is also homozygous for C677T in MTHFR, hypothesize that the MTH FR polymorphism protects the patient against anaemia and speculate tha t homozygosity for MTHFR C677T could cause the dissociation between ha ematological and neurological disease seen in some patients with vitam in B12 deficiency.