Severe hyperhomocysteinemia due to cystathionine β-synthase deficiency, and Factor V Leiden mutation in a patient with recurrent venous thrombosis

Homocysteine is an amino acid that is toxic to vascular endothelial cells, and plasma elevations have been associated with venous thromboembolism. Severe hyperhomocysteinemia (>100 μmol/L) may result from mutations in the genes coding for enzymes in the trans-sulfuration or the folate/vitamin B12-dependent re-methylation pathways. Here, we report the case of a young woman with severe, recurrent thrombo-embolic events associated with severe hyperhomocysteinemia (111 μmol/L). We identified a homozygous mutation in the cystathionine β -synthase gene (p.I278T) 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 β -synthase gene. Management consisted of anticoagulation with warfarin and supplementation with folate, vitamin B6 (pyridoxine) and vitamin B12. After twelve years of follow-up, plasma homocysteine levels remain in the moderate range (~20 μmol/L, reference range 8-12 μmol/L) and no further thromboembolic events were identified.