Abstract
Homocysteine is an amino acid that is toxic to vascular endothelial cells, and plasma elevations have been associated with venous thromboembolism. Severe hyperhomocysteinemia (>100 mu mol/L) may result from mutations in the genes coding for enzymes in the trans-sulfuration or the folate/vitamin B-12-dependent re-methylation pathways. Here, we report the case of a young woman with severe, recurrent thrombo-embolic events associated with severe hyperhomocysteinemia (111 mu mol/L). We identified a homozygous mutation in the cystathionine beta -synthase gene (p.1278T) and the presence of the Factor V Leiden mutation. Family study shows segregation of elevated homocysteine in heterozygous relatives for the mutation in the cystathionine beta -synthase gene. Management consisted of anticoagulation with warfarin and supplementation with folate, vitamin B-6 (pyridoxine) and vitamin B-12. After twelve years of follow- up, plasma homocysteine levels remain in the moderate range (similar to 20 mu mol/L, reference range 8-12 mu mol/L) and no further thromboembolic events were identified.