Open AccessNationwide screening for Fabry disease in unselected stroke patients
Author(s) -
Aleš Tomek,
Petra Reková,
Jaroslava Paulasová Schwabová,
Anna Olšerová,
Miroslav Škorňa,
Miroslava Nevšímalová,
Libor Šimůnek,
Roman Herzig,
Štěpánka Fafejtová,
Petr Mikulenka,
Alena Táboříková,
Jiří Neumann,
Richard Brzezny,
Helena Sobolová,
Jan Bartoník,
Daniel Václavík,
Marta Vachová,
Karel Bechyně,
Hana Havlíková,
Tomáš Prax,
Daniel Šaňák,
Irena Černíková,
Iva Ondečková,
Petr Procházka,
Jan Rajner,
Miroslav Škoda,
Jan Novák,
Ondřej Škoda,
Michal Bar,
Robert Mikulík,
Gabriela Dostálová,
Aleš Linhart,
AUTHOR_ID
Publication year - 2021
Publication title -
plos one
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.99
H-Index - 332
ISSN - 1932-6203
DOI - 10.1371/journal.pone.0260601
Subject(s) - fabry disease , medicine , stroke (engine) , intracerebral hemorrhage , subarachnoid hemorrhage , gastroenterology , venous thrombosis , vascular disease , disease , thrombosis , mechanical engineering , engineering
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.