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

Affiliations

08 November 2021

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doi: 10.7759/cureus.19358


Abstract

Fabry disease (FD) is an X-linked disorder involving multiple organs. Stroke is a serious and frequent complication of FD. Cryptogenic stroke is a common presentation of FD, especially in the young population. The etiology of cryptogenic stroke is highly variable and difficult to assess, frequently leaving patients without a primary diagnosis. We conducted a systematic review to investigate the pooled prevalence of FD among patients with cryptogenic stroke, or patients with FD in whom a stroke was the presenting condition. English-language studies involving humans published in the last 20 years were included in this systematic review. FD was more common in male patients and tended to present at an earlier age. The frequency of hemorrhagic and ischemic strokes in this population was similar to that in the general population. There was a high rate of stroke recurrence in the study sample, even among patients undergoing enzyme replacement therapy. We conclude that screening for FD in patients with cryptogenic stroke is low yield and not cost-effective. However, it may be worthwhile to screen for FD among patients with recurrent strokes.

Keywords: alpha-galactosidase; cryptogenic stroke; fabry disease; ischemic stroke; stroke.

Conflict of interest statement

The authors have declared that no competing interests exist.


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References

  1.  
    1. The frequency of Fabry disease among young cryptogenic stroke patients in the city of Sakarya. Gündoğdu AA, Kotan D, Alemdar M. J Stroke Cerebrovasc Dis. 2017;26:1334–1340. - PubMed
  2.  
    1. Prevalence of Fabry disease in young patients with cryptogenic ischemic stroke. Dubuc V, Moore DF, Gioia LC, Saposnik G, Selchen D, Lanthier S. J Stroke Cerebrovasc Dis. 2013;22:1288–1292. - PubMed
  3.  
    1. Fabry disease: molecular basis, pathophysiology, diagnostics and potential therapeutic directions. Kok K, Zwiers KC, Boot RG, Overkleeft HS, Aerts JM, Artola M. Biomolecules. 2021;11:271. - PMC - PubMed
  4.  
    1. Increased signal intensity in the pulvinar on T1-weighted images: a pathognomonic MR imaging sign of Fabry disease. Moore DF, Ye F, Schiffmann R, Butman JA. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8149001/ AJNR Am J Neuroradiol. 2003;24:1096–1101. - PMC - PubMed
  5.  
    1. Case report: first two identified cases of Fabry disease in Central Asia. Cainelli F, Argandykov D, Kaldarbekov D, Mukarov M, Tran Thi Phuong L, Germain DP. Front Genet. 2021;12:657824. - PMC - PubMed
  6.  
    1. Diagnosis and screening of patients with Fabry disease. Vardarli I, Rischpler C, Herrmann K, Weidemann F. Ther Clin Risk Manag. 2020;16:551–558. - PMC - PubMed
  7.  
    1. Fabry disease: recognition, diagnosis, and treatment of neurological features. Ranieri M, Bedini G, Parati EA, Bersano A. Curr Treat Options Neurol. 2016;18:33. - PubMed
  8.  
    1. Stroke and Fabry disease. Viana-Baptista M. J Neurol. 2012;259:1019–1028. - PubMed
  9.  
    1. MOOSE reporting guidelines for meta-analyses of observational studies. Brooke BS, Schwartz TA, Pawlik TM. https://jamanetwork.com/journals/jamasurgery/article-abstract/2778476. JAMA Surg. 2021;156:787–788. - PubMed
  10.  
    1. ROBINS-I: a tool for assessing risk of bias in non-randomised studies of interventions. Sterne JA, Hernán MA, Reeves BC, et al. BMJ. 2016;355:0. - PMC - PubMed
  11.  
    1. Prevalence of Fabry disease and outcomes in young Canadian patients with cryptogenic ischemic cerebrovascular events. Lanthier S, Saposnik G, Lebovic G, Pope K, Selchen D, Moore DF. Stroke. 2017;48:1766–1772. - PubMed
  12.  
    1. Screening for Fabry disease in young strokes in the Australian Stroke Clinical Registry (AuSCR) Malavera A, Cadilhac DA, Thijs V, et al. Front Neurol. 2020;11:596420. - PMC - PubMed
  13.  
    1. Prevalence of Fabry disease in patients with cryptogenic stroke: a prospective study. Rolfs A, Böttcher T, Zschiesche M, et al. Lancet. 2005;366:1794–1796. - PubMed
  14.  
    1. Screening for Fabry disease in Japanese patients with young-onset stroke by measuring α-galactosidase A and globotriaosylsphingosine. Kinoshita N, Hosomi N, Matsushima H, et al. J Stroke Cerebrovasc Dis. 2018;27:3563–3569. - PubMed
  15.  
    1. The prevalence of Fabry disease among young cryptogenic stroke patients. Alhazzaa MA, Mujtaba A, Aljohani MA, Alqarni F, Alsharif R. Cureus. 2020;12:0. - PMC - PubMed
  16.  
    1. Middelheim Fabry Study (MiFaS): a retrospective Belgian study on the prevalence of Fabry disease in young patients with cryptogenic stroke. Brouns R, Sheorajpanday R, Braxel E, et al. Clin Neurol Neurosurg. 2007;109:479–484. - PubMed
  17.  
    1. Zurich Fabry study - prevalence of Fabry disease in young patients with first cryptogenic ischaemic stroke or TIA. Sarikaya H, Yilmaz M, Michael N, Miserez AR, Steinmann B, Baumgartner RW. Eur J Neurol. 2012;19:1421–1426. - PubMed
  18.  
    1. Prevalence of Fabry disease in young patients with stroke in Argentina. Reisin RC, Mazziotti J, Cejas LL, et al. J Stroke Cerebrovasc Dis. 2018;27:575–582. - PubMed
  19.  
    1. Frequency of unrecognized Fabry disease among young European-American and African-American men with first ischemic stroke. Wozniak MA, Kittner SJ, Tuhrim S, et al. Stroke. 2010;41:78–81. - PMC - PubMed
  20.  
    1. Characteristics of neurological symptoms in adult Japanese patients with Fabry disease. Sawada J, Nakagawa N, Kano K, et al. Intern Med. 2021;60:1819–1826. - PMC - PubMed
  21.  
    1. Reduced cerebral blood flow velocity and impaired cerebral autoregulation in patients with Fabry disease. Hilz MJ, Kolodny EH, Brys M, Stemper B, Haendl T, Marthol H. J Neurol. 2004;251:564–570. - PubMed
  22.  
    1. Vasculopathy in patients with Fabry disease: current controversies and research directions. Rombach SM, Twickler TB, Aerts JM, Linthorst GE, Wijburg FA, Hollak CE. Mol Genet Metab. 2010;99:99–108. - PubMed
  23.  
    1. Fabry disease and early stroke. Feldt-Rasmussen U. Stroke Res Treat. 2011;2011:615218. - PMC - PubMed
  24.  
    1. Stroke in Fabry disease frequently occurs before diagnosis and in the absence of other clinical events: natural history data from the Fabry Registry. Sims K, Politei J, Banikazemi M, Lee P. Stroke. 2009;40:788–794. - PubMed
  25.  
    1. Genomic screening of Fabry disease in young stroke patients: the Taiwan experience and a review of the literature. Lee TH, Yang JT, Lee JD, et al. Eur J Neurol. 2019;26:553–555. - PMC - PubMed
  26.  
    1. Acute cerebrovascular disease in the young: the Stroke in Young Fabry Patients study. Rolfs A, Fazekas F, Grittner U, et al. Stroke. 2013;44:340–349. - PubMed
  27.  
    1. Dietary magnesium intake and risk of cardiovascular disease among women. Song Y, Manson JE, Cook NR, Albert CM, Buring JE, Liu S. Am J Cardiol. 2005;96:1135–1141. - PubMed
  28.  
    1. Fabry's disease and stroke: effectiveness of enzyme replacement therapy (ERT) in stroke prevention, a review with meta-analysis. Sheng S, Wu L, Nalleballe K, et al. J Clin Neurosci. 2019;65:83–86. - PubMed
  29.  
    1. Time to treatment benefit for adult patients with Fabry disease receiving agalsidase β: data from the Fabry Registry. Ortiz A, Abiose A, Bichet DG, et al. J Med Genet. 2016;53:495–502. - PMC - PubMed