European Journal of Pediatrics

, Volume 156, Issue 12, pp 925–930 | Cite as

Methionine synthase deficiency without megaloblastic anaemia

  • E. A. Kvittingen
  • S. Spangen
  • J. Lindemans
  • B. Fowler


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.

Key words Methionine synthase 10 Methylenetetrahydrofolate Megaloblastic anaemia Polymorphism Homocysteine 

Copyright information

© Springer-Verlag Berlin Heidelberg 1997

Authors and Affiliations

  • E. A. Kvittingen
    • 1
  • S. Spangen
    • 2
  • J. Lindemans
    • 3
  • B. Fowler
    • 4
  1. 1.Institute of Clinical Biochemistry, University of Oslo, Rikshospitalet, N-0027 Oslo, Norway, Tel.: +47 2286 7036, Fax: +47 2286 7029NO
  2. 2.Department of Paediatrics, Aalesund Regional Hospital, NorwayNO
  3. 3.Institute of Haematology, Erasmus University, Rotterdam, The NetherlandsNL
  4. 4.Basler Kinderspital, Basel, SwitzerlandCH

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