Nationwide screening for Fabry disease in unselected stroke patients

Autoři	TOMEK Ales REKOVÁ Petra PAULASOVÁ SCHWABOVÁ Jaroslava OLŠEROVÁ Anna ŠKORŇA Miroslav NEVŠÍMALOVÁ Miroslava ŠIMŮNEK Libor HERZIG Roman FAFEJTOVÁ Štěpánka MIKULENKA Petr TÁBOŘÍKOVÁ Alena NEUMANN Jiří BRZEZNY Richard SOBOLOVÁ Helena BARTONÍK Jan VÁCLAVÍK Daniel VACHOVÁ Marta BECHYNĚ Karel HAVLÍKOVÁ Hana PRAX Tomáš ŠAŇÁK Daniel ČERNÍKOVÁ Irena ONDEČKOVÁ Iva PROCHÁZKA Petr RAJNER Jan ŠKODA Miroslav NOVÁK Jan ŠKODA Ondřej BAR Mcihal MIKULÍK Robert DOSTÁLOVÁ Gabriela LINHART Aleš
Rok publikování	2021
Druh	Článek v odborném periodiku
Časopis / Zdroj	PLOS ONE
Fakulta / Pracoviště MU	Lékařská fakulta
Citace
www	https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0260601
Doi	http://dx.doi.org/10.1371/journal.pone.0260601
Klíčová slova	Fabry disease; stroke patients; screening
Popis	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.