Metylenetetrahydrofolate Reductase Polymorphism and Venous Thrombosis in Children

The venous thromboembolism is a serious and complex pathological condition especially for its potential complications. It is related to both congenital and acquired factors. Among the congenital factors, different mutations have been identified leading to a reduced activity of enzymes (even higher than 50%) involved in the homocysteine-methyonine methabolic pathway, such as the methylenetetrahydrofolate reductase enzyme (MTHFR).

The homozygotic TT genotype is found in approximately 10–12% of the population and is associated with a 25% higher homocisteine level in these patients than those without this mutation. The heterozygotic genotype is found in 40% of the population. The aim of this study is to define in children the correlation between venous thrombosis and MTHFR mutations. Between december 2002 and april 2008 nine children aged between 1–132 months were admitted in the Department of Hematology of Children Hospital Bambino Gesù in Rome. They were affected by deep venous thrombosis and were submitted to thrombophilic screening and vascular imaging. The MTHFR polymorphism C677CT was found in all the patients (four in homozygosis and seven in heterozygosis) and also in their parents. Four heterozygous and three homozygous patients presented increased plasmatic and urinary levels of homocysteine. Since venous thrombosis was only referred in the clinical history, two patients did not received treatments. Nine were treated with low molecular weight heparin (enoxaparin 100 U/kg s.c. × 2 daily), then seven continued the treatment with oral anticoagulant for 6–12 months and all of them performed long term profilaxis with folic acid and B group vitamins. Only one patient presented further thrombotic event and restarded the oral anticoagulant therapy. These data confirm that the measurement of homocysteinemia and MTHFR may be indicated in unexplained idiopathic venous thrombosis or recurrent episodes or venous thrombosis occurred at an early age or at an uncommon site. It is to be discussed whether to perform anticoagulant profilaxis in all patients with MTHFR mutation, in homozygosis or heterozygosis, with or without hyperhomocysteinaemia, with previous thrombotic events, with other thrombotic risk factors (pregnancy, oral contracceptives, sepsis and immobilization). In addition in presence of hyperhomocysteinemia, it might be reccomended to perform therapy with folic acid and B6 vitamin.