ABSTRACT. High plasma homocysteine (Hcy) levels may be responsible for vaso-occlusive episodes and may have acquired and/or genetic causes. This cross-sectional study aimed to investigate the role of methylenetetrahydrofolate reductase (MTHFR; C677T; A1298C) and cystathionine-b-synthase (CBS; T833C/844ins68, G919A) polymorphisms in serum levels of folic acid, vitamin B12 and Hcy, and to verify a possible association between these polymorphisms and the clinical variability. Blood samples of Brazilian patients with a diagnosis of thrombosis were submitted to genotyping by PCR-based methods and serum dosages of folic acid, vitamin B12 and Hcy. Except for the CBS G919A polymorphism, all other genetic markers were in HardyWeinberg equilibrium. An increased risk for venous thrombosis was found for the MTHFR 1298CC carriers (OR = 1.688; 95%CI = 0.839-3.398, P = 0.018) and those homozygously mutant for the CBS haplotype 844ins68/T833C (OR = 2.488; 95%CI = 0.501-12.363, P = 0.031), while heterozygous for this CBS haplotype showed an increased risk for higher Hcy levels (OR = 5.900; 95%CI = 1.003-34.691, P = 0.030). Significant interactions were observed among the MTHFR C677T, MTHFR A1298C and CBS haplotype 844ins68/T833C polymorphisms in the results for Hcy levels (P = 0.000), where heterozygous had higher values. Interactions among these polymorphisms can affect serum Hcy levels, where multiple heterozygosis could be a risk factor for vasoocclusive episodes.

Hereditary thrombophilia is the inherited predisposition to venous or, occasionally, arterial thrombosis. In most cases, it is because of changes related to physiological coagulation inhibitors or mutations in genes of coagulation factors. Protein S, a vitamin K-dependent plasma glycoprotein, is a natural anticoagulant and its deficiency is associated with familial venous thrombosis. We present a case study that brings together two rare diseases, cerebral venous thrombosis (CVT) and familial protein S deficiency, in a 21-year-old male patient with a positive family history of thrombosis. He developed a headache of moderate intensity lasting 30 days, followed by bizarre movements, which culminated in the patient's death. This report discusses the importance of family history for the diagnosis of hereditary thrombophilia, as well as the request for brain imaging for diagnosis of CVT for an early appropriate intervention, and the importance of specialized medical guidance for family members, who must receive medical advice to prevent another fatal episode in a family member.