Molecular genetics of methylenetetrahydrofolate reductase deficiency

J Inherit Metab Dis. 1996;19(5):589-94. doi: 10.1007/BF01799831.


In severe MTHFR deficiency with neonatal or adolescent onset, 9 rare mutations have been identified. In mild MTHFR deficiency with thermolabile enzyme, a single common mutation (an alanine-to-valine substitution) is involved, but a genetic-nutrient interactive effect is required to produce mild hyperhomocysteinaemia. This interactive effect has been proposed to be a risk factor for arteriosclerosis and for neural-tube defects. Large-scale studies are required for confirmation of the role of MTHFR in these multifactorial processes as well as to assess its role in other folate-dependent disorders.

Publication types

  • Review

MeSH terms

  • Animals
  • Arteriosclerosis / etiology
  • DNA, Complementary / genetics
  • Genetic Variation
  • Homocystinuria / complications
  • Homocystinuria / enzymology
  • Homocystinuria / genetics
  • Humans
  • Methylenetetrahydrofolate Reductase (NADPH2)
  • Molecular Biology
  • Mutation
  • Oxidoreductases Acting on CH-NH Group Donors / deficiency*
  • Oxidoreductases Acting on CH-NH Group Donors / genetics*
  • Temperature


  • DNA, Complementary
  • Oxidoreductases Acting on CH-NH Group Donors
  • Methylenetetrahydrofolate Reductase (NADPH2)