Methionine synthase deficiency without megaloblastic anaemia.

[homocystinuria without methylmalonic aciduria]

We report findings on a child presenting with neonatal homocystinuria , hypomethioninaemia and severe neurological symptoms , including developmental delay and seizures . Methylmalonic aciduria was not present . The activity of methionine synthase in fibroblasts was severely deficient and formation of methylcobalamin from 57 Co labelled cyanocobalamin was very low . The patients cells complemented with those of a cblE patient but not with those of two cblG patients . No biochemical or clinical response to injections of hydroxycobalamin was found . Both off treatment and on betaine and methionine supplementation the patient , at age 8 years , has not developed megaloblastic anaemia . In addition , the patient is homozygous for the C 6 77 T polymorphism in the 5 ,10 methylenetetrahydrofolate reductase (MTHFR ) gene and the concomitant existence of this mutation with the methionine synthase defect may prevent folate <trapping > and thus anaemia .We report the lack of megaloblastic anaemia in a patient with severe methionine synthase deficiency who is also homozygous for C 6 77 T in MTHFR , hypothesize that the MTHFR polymorphism protects the patient against anaemia and speculate that homozygosity for MTHFR C 6 77 T could cause the dissociation between haematological and neurological disease seen in some patients with vitamin B 12 deficiency .