Prevalence of Fabry Disease in Young Patients with Cryptogenic Ischemic Stroke

Background A German study diagnosed 4% of young cryptogenic ischemic stroke patients with Fabry disease, an X-linked lysosomal storage disease caused by mutations in the alpha-galactosidase A ( α-GAL-A ) gene resulting in an accumulation of glycosphingolipids. A lower prevalence was found in other geographic regions. Aim To determine the prevalence of Fabry disease in a Canadian population of young cryptogenic ischemic stroke patients. Materials and Methods Patients with cryptogenic ischemic stroke at age 16-55 were retrospectively identified in our institutional stroke database and underwent a focused clinical evaluation. We sequenced the α-GAL-A gene and measured the levels of blood globotriaosylsphingosine in subjects with mutations of undetermined pathogenicity. Fabry disease was diagnosed in patients with pathogenic mutations or increased levels of blood globotriaosylsphingosine. Results Ninety-three of 100 study subjects had normal α-GAL-A gene polymorphisms. Seven had mutations of undetermined pathogenicity, including one with increased globotriaosylsphingosine (prevalence, 1%; 95% confidence interval, α-GAL-A genes. Apart from the 100 study subjects, our database included another patient with a family history of Fabry disease and a pathogenic mutation identified before her ischemic stroke presentation as the first clinical manifestation of Fabry disease. Both Fabry patients experienced recurrent ischemic stroke. Conclusions Fabry disease accounts for a small proportion of young Canadians with cryptogenic ischemic stroke. Identification of Fabry biomarkers remains a research priority to delineate stroke patients disserving routine screening.