Screening for Fabry Disease in Young Strokes in the Australian Stroke Clinical Registry (AuSCR)

Frontiers in Neurology

Vincent Thijs¹  Joyce Y. Lim²  Alejandra Malavera²  Dominique A. Cadilhac³  Brenda Grabsch³  Sibilah Breen³  Craig S. Anderson⁴  Stephen Jan⁶ 

[1] Department of Neurology, Austin Health Heidelberg, Heidelberg, VIC, Australia;Faculty of Medicine, The George Institute for Global Health, University of New South Wales, Sydney, NSW, Australia;Florey Institute of Neuroscience and Mental Health, University of Melbourne, Heidelberg, VIC, Australia;Neurology Department, Royal Prince Alfred Hospital, Sydney Health Partners, Sydney, NSW, Australia;Stroke and Ageing Research, Department of Medicine, School of Clinical Sciences at Monash Health, Monash University, Clayton, VIC, Australia;Sydney Medical School, University of Sydney, Sydney, NSW, Australia;

关键词: fabry disease;    α-galactosidase A;    screening;    blood spot test;    GLA gene;    young stroke;   

DOI  :  10.3389/fneur.2020.596420

来源: DOAJ

【 摘 要 】

Introduction: Fabry disease (FD) is an X-linked lysosomal storage disorder characterized by a deficiency or absence of alpha-galactosidase A (α-GAL A) enzyme, where stroke can be a serious complication. The aim of this study is to determine the feasibility of centralized screening for FD, among young stroke adults registered in the national Australian Stroke Clinical Registry (AuSCR).Methods: The study was conducted in young (age 18 – 55 years) survivors of acute stroke of unknown etiology registered in AuSCR at hospitals in Queensland, Tasmania, New South Wales, and Victoria during 2014 – 2015; and who, at the 3-month outcome assessment, agreed to be re-contacted for future research. Descriptive analyses of case identification from responses and specific enzyme and DNA sequencing analyses were conducted for α-galactosidase A (α-GLA) from dried blood spot (DBS) testing.Results: Of 326 AuSCR-identified patients invited to participate, 58 (18%) provided consent but six were subsequently unable to provide a blood sample and two later withdrew consent to use their data. Among the remaining 50 participants (median age 53 years [48 – 56 years]; 47% female), 67% had experienced an acute ischemic stroke. All males (n = 27) had an initial screen for α-GLA enzyme activity of whom seven with low enzyme levels had normal secondary α-GLA gene analysis. All females (n = 23) had genetic analysis, with one shown to have a pathogenic c.352C>T p.(Arg118Cys) missense mutation of the α-GLA gene for FD.Conclusions: These findings provide logistical data for embedding a process of automated central stroke registry screening for an additional case-finding tool in FD.

【 授权许可】

Unknown