Stroke in Fabry Disease Frequently Occurs Before Diagnosis and in the Absence of Other Clinical Events Natural History Data From the Fabry Registry

Background and Purpose-Stroke is a common and serious clinical manifestation of Fabry disease, an X-linked lysosomal storage disorder caused by deficiency of alpha-galactosidase A activity. This study was undertaken to better understand the natural history of cerebrovascular manifestations of Fabry disease. Methods-Data from 2446 patients in the Fabry Registry were analyzed to identify clinical characteristics of patients experiencing stroke during the natural history period (ie, before enzyme replacement therapy). Results-A total of 138 patients (86 of 1243 males [ 6.9%] and 52 of 1203 females [ 4.3%]) experienced strokes. Median age at first stroke was 39.0 years in males and 45.7 years in females. Most patients (70.9% of males and 76.9% of females) had not experienced renal or cardiac events before their first stroke. Fifty percent of males and 38.3% of females experienced their first stroke before being diagnosed with Fabry disease. Thirty patients (21 males and 9 females) had strokes at age <30 years. Most patients (86.8%) had ischemic strokes, but 16.9% of males and 6.9% of females had hemorrhagic strokes, among those for whom stroke type was reported. At the most recently available follow-up examination after their first stroke, 60% of males and 25.5% of females exhibited stage 3 to 5 chronic kidney disease and 66.1% of males and 59.5% of females had left ventricular hypertrophy. Conclusions-All patients with Fabry disease, regardless of age or gender, should be monitored for possible cerebrovascular complications, as stroke can occur in the absence of other key signs of the disease. (Stroke. 2009; 40: 788-794.)