Isolated thrombosis due to the cystathionine β-synthase mutation c.833T>C (I278T)

Hereditary homocystinuria due to cystathionine β-synthase (CBS) deficiency is a rare disease (about 1:20 000 in Germany) often complicated by thromboembolism. Single mutations, which affect the C-terminal region of the CBS enzyme, lead to isolated thrombosis without further symptoms typical for homocystinuria such as atherosclerosis, psychomotor retardation, and dislocation of the ocular lenses. In this study, DNA samples of patients with stroke (n=225) and sinus thrombosis (n=46) were screened for the most common homocystinuria mutation, CBS I278T. In each group one homozygous patient was identified. Thus, not only C-terminal mutations but also the most common mutation in classical homocystinuria, CBS I278T, can lead to isolated thrombophilic events. These data support the hypothesis that homocystinuria is an underdiagnosed disease.