BACKGROUND AND AIMS: Fabry disease (FD) is a rare X-linked lysosomal storage disorder caused by disease-associated variants in the alpha-galactosidase A gene (GLA). FD is a known cause of stroke in younger patients. There are limited data on prevalence of FD and stroke risk in unselected stroke patients. METHODS: A prospective nationwide study including 35 (78%) of all 45 stroke centers and all consecutive stroke patients admitted during three months. Clinical data were collected in the RES-Q database. FD was diagnosed using dried blood spots in a stepwise manner: in males-enzymatic activity, globotriaosylsphingosine (lyso-Gb3) quantification, if positive followed by GLA gene sequencing; and in females GLA sequencing followed by lyso-Gb3. RESULTS: 986 consecutive patients (54% men, mean age 70 years) were included. Observed stroke type was ischemic 79%, transient ischemic attack (TIA) 14%, intracerebral hemorrhage (ICH) 7%, subarachnoid hemorrhage 1% and cerebral venous thrombosis 0.1%. Two (0.2%, 95% CI 0.02-0.7) patients had a pathogenic variant associated with the classical FD phenotype (c.1235_1236delCT and p.G325S). Another fourteen (1.4%, 95% CI 0.08-2.4) patients had a variant of GLA gene considered benign (9 with p.D313Y, one p.A143T, one p.R118C, one p.V199A, one p.R30K and one p.R38G). The index stroke in two carriers of disease-associated variant was ischemic lacunar. In 14 carriers of GLA gene variants 11 strokes were ischemic, two TIA, and one ICH. Patients with positive as compared to negative GLA gene screening were younger (mean 60±SD, min, max, vs 70±SD, min, max, P = 0.02), otherwise there were no differences in other baseline variables. CONCLUSIONS: The prevalence of FD in unselected adult patients with acute stroke is 0.2%. Both patients who had a pathogenic GLA gene variant were younger than 50 years. Our results support FD screening in patients that had a stroke event before 50 years of age.

1st Faculty of Medicine 2nd Department of Medicine Department of Cardiovascular Medicine Charles University and General University Hospital Prague Czech Republic

1st Faculty of Medicine Department of Neurology and Center of Clinical Neuroscience Charles University and General University Hospital Prague Czech Republic

2nd Faculty of Medicine Department of Neurology Charles University and University Hospital Motol Prague Czech Republic

3rd Medical Faculty Department of Neurology Neurology Dpt Charles University and University Hospital Kralovské Vinohrady Prague Czech Republic

D epartment of Neurology University Hospital Ostrava and Faculty of Medicine Ostrava University Ostrava Czech Republic

Department of Neurology AGEL Research and Training Institute Ostrava Vítkovice Hospital Ostrava Czech Republic

Department of Neurology Hospital České Budějovice České Budějovice Czech Republic

Department of Neurology Hospital Jihlava Jihlava Czech Republic

Department of Neurology Hospital Písek Písek Czech Republic

Department of Neurology Krajská zdravotní a s Hospital Děčín Děčín Czech Republic

Department of Neurology Krajská zdravotní a s Hospital Teplice Teplice Czech Republic

Department of Neurology Municipal Hospital Ostrava Ostrava Czech Republic

Department of Neurology Neurology Dpt Hospital Třinec Třinec Czech Republic

Department of Neurology Neurology Dpt Krajská zdravotní a s Hospital Chomutov Chomutov Czech Republic

Department of Neurology Neurology Dpt Regional Hospital Kladno Kladno Czech Republic

Department of Neurology Neurology Dpt Regional Hospital of Tomáš Baťa Zlín Czech Republic

Department of Neurology Palacký University Medical School and Hospital Olomouc Czech Republic

Department of Neurology Regional Hospital Česká Lípa Česká Lípa Czech Republic

Department of Neurology Regional Hospital Karlovy Vary Karlovy Vary Czech Republic

Department of Neurology Regional Hospital Kolín Kolín Czech Republic

Department of Neurology Regional Hospital Liberec Liberec Czech Republic

Department of Neurology Regional Hospital Náchod Náchod Czech Republic

Department of Neurology Regional Hospital Pardubice Pardubice Czech Republic

Department of Neurology Regional Hospital Uherské Hradiště Uherské Hradiště Czech Republic

Department of Neurology University Hospital Brno and Faculty of Medicine Masaryk University Brno Czech Republic

Faculty of Medicine in Hradec Králové and University Hospital Hradec Králové Department of Neurology Hradec Králové Czech Republic

International Clinical Research Center and Department of Neurology St Anne's University Hospital and Medical Faculty of Masaryk University Brno Czech Republic

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$a BACKGROUND AND AIMS: Fabry disease (FD) is a rare X-linked lysosomal storage disorder caused by disease-associated variants in the alpha-galactosidase A gene (GLA). FD is a known cause of stroke in younger patients. There are limited data on prevalence of FD and stroke risk in unselected stroke patients. METHODS: A prospective nationwide study including 35 (78%) of all 45 stroke centers and all consecutive stroke patients admitted during three months. Clinical data were collected in the RES-Q database. FD was diagnosed using dried blood spots in a stepwise manner: in males-enzymatic activity, globotriaosylsphingosine (lyso-Gb3) quantification, if positive followed by GLA gene sequencing; and in females GLA sequencing followed by lyso-Gb3. RESULTS: 986 consecutive patients (54% men, mean age 70 years) were included. Observed stroke type was ischemic 79%, transient ischemic attack (TIA) 14%, intracerebral hemorrhage (ICH) 7%, subarachnoid hemorrhage 1% and cerebral venous thrombosis 0.1%. Two (0.2%, 95% CI 0.02-0.7) patients had a pathogenic variant associated with the classical FD phenotype (c.1235_1236delCT and p.G325S). Another fourteen (1.4%, 95% CI 0.08-2.4) patients had a variant of GLA gene considered benign (9 with p.D313Y, one p.A143T, one p.R118C, one p.V199A, one p.R30K and one p.R38G). The index stroke in two carriers of disease-associated variant was ischemic lacunar. In 14 carriers of GLA gene variants 11 strokes were ischemic, two TIA, and one ICH. Patients with positive as compared to negative GLA gene screening were younger (mean 60±SD, min, max, vs 70±SD, min, max, P = 0.02), otherwise there were no differences in other baseline variables. CONCLUSIONS: The prevalence of FD in unselected adult patients with acute stroke is 0.2%. Both patients who had a pathogenic GLA gene variant were younger than 50 years. Our results support FD screening in patients that had a stroke event before 50 years of age.

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