Symptomatic and asymptomatic methylenetetrahydrofolate reductase deficiency in two adult brothers

Am J Med Genet. 1993 Mar 1;45(5):572-6. doi: 10.1002/ajmg.1320450510.


We describe two brothers with 5,10-methylene tetrahydrofolate reductase (MTHFR) deficiency. The younger patient first developed limb weakness, incoordination, paresthesiae, and memory lapses at age 15 years, and by his early twenties he was wheelchair bound. His older brother remains asymptomatic at age 37 years. Both had homocystinuria and homocystinemia and low plasma levels of methionine. MTHFR activities in cultured skin fibroblasts of both patients were < 10% control and residual enzyme activities were markedly reduced on heating. The parents had intermediate enzyme activities and the reductase in the father (who had unexplained paraparesis and homocystinemia), but not in the mother, was also thermolabile. Both patients were treated with oral folate and betaine which improved, but did not totally correct, their biochemical abnormality. MTHFR deficiency should be considered in the differential diagnosis of unexplained neurologic disease in adolescents and adults.

Publication types

  • Case Reports
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Betaine / therapeutic use
  • Enzyme Stability
  • Folic Acid / therapeutic use
  • Homocystine / metabolism
  • Humans
  • Male
  • Metabolism, Inborn Errors / drug therapy
  • Metabolism, Inborn Errors / genetics*
  • Metabolism, Inborn Errors / metabolism
  • Methionine / blood
  • Methylenetetrahydrofolate Reductase (NADPH2)
  • Nervous System Diseases / drug therapy
  • Nervous System Diseases / genetics*
  • Nervous System Diseases / metabolism
  • Oxidoreductases Acting on CH-NH Group Donors / deficiency*
  • Paraparesis, Tropical Spastic / drug therapy
  • Paraparesis, Tropical Spastic / genetics
  • Paraparesis, Tropical Spastic / metabolism


  • Betaine
  • Homocystine
  • Folic Acid
  • Methionine
  • Oxidoreductases Acting on CH-NH Group Donors
  • Methylenetetrahydrofolate Reductase (NADPH2)