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 57Co 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 C677T 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.
CONCLUSION: 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.