Homozygous cystathionine beta-synthase deficiency, combined with factor V Leiden or thermolabile methylenetetrahydrofolate reductase in the risk of venous thrombosis

Blood. 1998 Mar 15;91(6):2015-8.


Severe hyperhomocysteinemia in its most frequent form, is caused by a homozygous enzymatic deficiency of cystathionine beta-synthase (CBS). A major complication in CBS deficiency is deep venous thrombosis or pulmonary embolism. A recent report by Mandel et al (N Engl J Med 334:763, 1996) postulated factor V Leiden (FVL) to be an absolute prerequisite for the development of thromboembolism in patients with severe hyperhomocysteinemia. We studied 24 patients with homocystinuria caused by homozygous CBS deficiency from 18 unrelated kindreds for FVL and for the 677C-->T mutation in the methylenetetrahydrofolate reductase (MTHFR) gene and investigated their possible interaction in the risk of venous thrombosis. Thrombotic complications were diagnosed in six patients, of whom only one was a carrier of FVL. On the contrary, thermolabile MTHFR caused by the 677C-->T mutation, was frequently observed among homocystinuria patients, especially among those with thromboembolic complications: three of six homocystinuria patients who had suffered from a thromboembolic event had thermolabile MTHFR. These data indicate that FVL is not an absolute prerequisite and probably not even a major determinant of venous thrombosis in homocystinuria, but, interestingly, thermolabile MTHFR may constitute a significant risk factor for thromboembolic complications in this inborn error of methionine metabolism.

MeSH terms

  • Adolescent
  • Adult
  • Child, Preschool
  • Cystathionine beta-Synthase / deficiency*
  • DNA Mutational Analysis
  • Factor V / analysis*
  • Female
  • Homocysteine / blood*
  • Homocystinuria / complications
  • Homozygote
  • Hot Temperature
  • Humans
  • Male
  • Methylenetetrahydrofolate Reductase (NADPH2)
  • Middle Aged
  • Oxidoreductases Acting on CH-NH Group Donors / chemistry
  • Oxidoreductases Acting on CH-NH Group Donors / genetics*
  • Point Mutation
  • Protein Denaturation
  • Pulmonary Embolism / blood
  • Pulmonary Embolism / enzymology
  • Pulmonary Embolism / epidemiology*
  • Pulmonary Embolism / genetics
  • Risk Factors
  • Thrombophilia / complications
  • Thrombophilia / epidemiology
  • Thrombophilia / genetics*
  • Thrombophlebitis / blood
  • Thrombophlebitis / enzymology
  • Thrombophlebitis / epidemiology*
  • Thrombophlebitis / genetics


  • factor V Leiden
  • Homocysteine
  • Factor V
  • Oxidoreductases Acting on CH-NH Group Donors
  • Methylenetetrahydrofolate Reductase (NADPH2)
  • Cystathionine beta-Synthase