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

Abstract

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.

Prevalence of Fabry Disease in Patients With Cryptogenic Strokes: A Systematic Review

“…Table 2 shows the age and sex, mutation, Gb3 levels and enzyme activity, infarct type, outcome (second stroke), long-term outcome, and treatment of patients included in the studies [1,2,[11][12][13]19]. Among the stroke patients, there were 32 ischemic infarcts (86.48%) and five hemorrhagic infarcts (13.51%).…”

“…Table 3 shows the bias of the studies included in this systematic review [1,2,[11][12][13][14][15][16]19].…”

“…shows the characteristics and outcomes of the cohorts investigated in this systematic review[1,2,[11][12][13][14][15][16][17][18][19].…”

High-Risk Screening for Fabry Disease: A Nationwide Study in Japan and Literature Review

“…We reviewed 19 studies [103][104][105][106][107][108][109][110][111][112][113][114][115][116][117][118][119][120][121] on high-risk screening in individuals with central neurological manifestations (Table 3). Most of these studies reported screening in individuals with idiopathic strokes.…”

“…Moreover, screening by α-Gal A activity and/or GLA sequencing of individuals with acute stroke or transient ischemic attack and aged 18 to 60 years demonstrated that three of 108 subjects (2.7%) harbored GLA pathogenic variants [111]. However, no GLA pathogenic variant was found in 10 screenings of individuals with central neurological manifestations [103][104][105][106]109,110,114,115,118,119]. Furthermore, p.R227Q was the most frequent variant detected in three individuals in Turkey and France [108,117], with this variant considered to be associated with the development of classical FD [42] and previously detected in one individual during the high-risk screening in individuals undergoing dialysis or kidney transplant in Turkey [53].…”