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

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.

Shedding Light on Inherited Thrombophilias

“…Homocysteine is an amino acid known to damage vascular endothelial cells, and plasma elevations have been associated with VTE. 9 Earlier reports linked MTHFR mutations with increased rates of stillbirth and eclampsia. 10 Current literature findings no longer support hyperhomocysteinemia as an isolated risk factor for VTE, most likely due to increased nutritional availability of folic acid inclusion in nutritional staples such as flour.…”

Classic homocystinuria: etiology, natural history and treatment

“…Таким образом, тромбозы и тромбоэмболические осложнения при классической гомоцистинурии могут развиться в детском возрасте, но чаще наблюдаются у взрослых, в том числе при отсутствии других типичных проявлений классической гомоцистинурии [17]. Дополнительным фактором риска тромбообразования может служить сопутствующая тромбофилия, например, мутация гена фактора V (фактора Лейдена) [18,19].…”