Fabry's disease: a prospective multicenter cohort study in young adults with cryptogenic stroke

Background: Stroke in young adults is etiologically diverse and may represent a diagnostic challenge remaining cryptogenic in one-fourth of cases. Limited information is available on the prevalence of Fabry's disease, a treatable multisystem inherited lysosomal storage disorder, and disability in young patients with cryptogenic stroke.

Design and methods: The Canadian Fabry Stroke Screening Initiative (CFSSI) is a prospective multicenter cohort study of young adults (age 18-55) presenting with an ischemic stroke, transient ischemic attack, or intracerebral haemorrhage of unknown etiology to stroke centres across Canada. Diagnosis of Fabry's disease is made by direct DNA analysis of blood samples for α-galactosidase gene mutations or polymorphisms. Demographics, clinical information, and investigations including brain Magnetic Resonance Imaging (MRI) are collected. Functional neurological assessment includes neurological examination, the National Institutes of Health (NIH) stroke scale, modified Rankin scale, and the Barthel index. A follow-up interview is conducted by telephone or in person approximately six-months after the index stroke/transient ischemic attack/intracerebral haemorrhage to determine patient outcomes, quality of life, and patient use of medications.

Main outcome: Prevalence of positive DNA mutation or single nucleotide polymorphism screens for Fabry's disease as a proportion of total cryptogenic stroke. Secondary outcomes include incident risk of new or recurrent vascular event at six-months, discharge disposition, disability at six-months as measured by the modified Rankin scale, mean time from symptoms onset to the definite etiological diagnosis, and length of hospital stay.

Conclusion: This study constitutes the first initiative to determine the prevalence of a positive screen for Fabry's disease in young adults with stroke in Canada. Moreover, the Canadian Fabry Stroke Screening Initiative will provide information on recurrent vascular events, disability at six-months (modified Rankin scale), and disposition in this understudied population.