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 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.
Highlights
Elevated free and protein-bond plasma homocysteine has been associated with venous thrombosis, pulmonary embolism and premature mortality
Case presentation Here, we present a 30-year follow up on a woman with recurrent venous thromboembolism associated with both severe hyperhomocysteinemia, and the Factor V Leiden (FVL) mutation
ID: number refers to Figure 2, LDL: low density lipoprotien cholesterol, tHcy: total homocysteine, CBS: cystathionine β-synthase gene mutation (p.I278T), methylenetetrahydrofolate reductase (MTHFR): methylenetetra-hydrofolate reductase C766T single nucleotide polymorphism, FVL: Factor V Leiden mutation
Summary
Elevated free and protein-bond plasma homocysteine (tHcy) has been associated with venous thrombosis, pulmonary embolism and premature mortality. Laboratory results showed levels of protein C and S within the reference ranges, and negative phospholipid antibodies. She was found to be heterozygous for the FVL mutation. Her tHcy level preceding her thrombophlebitis event was 54 μmol/L, and increased to 111 μmol/L within one year (reference range 4.6-15.5 μmol/L) (Figure 1 and Table 1). The proband had a homozygous (p.I278T) mutation in the CBS gene, a known vitamin B6-responsive mutation [2,3,4] In addition to this deleterious mutation at the CBS gene, the patient had coagulation FVL, a combination of findings traits shared by no other family members (Figure 2).
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
