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Monogenic Disorder: Fabry Disease

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Abstract

Fabry disease is an X-linked lysosomal storage disorder. In its “classical” form, a painful peripheral neuropathy develops in childhood or adolescence, along with non-neurological features. Later, life-threatening complications include renal failure, heart disease, and young-onset stroke. However, patients can present with stroke before a diagnosis of fabry disease has been reached. Despite its mode of inheritance, women with fabry disease may be severely affected, including presenting with young-onset stroke. Characteristic, albeit non-pathognomonic, MRI abnormalities in fabry disease include white matter lesions, pulvinar hyperintensity on T1-weighted images and vascular dolichoectasia. Enzyme replacement therapy has revolutionized the management of fabry disease, but its role in stroke prevention remains unclear.

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References

  1. MIM Number 301500 - Fabry Disease. Johns Hopkins University. http://www.omim.org/entry/301500. Accessed 6 Feb 2017

  2. EC 3.2.1.22. International Union of Biochemistry and Molecular Biology. http://www.chem.qmul.ac.uk/iubmb/enzyme/EC3/2/1/22.html. Accessed 6 Feb 2017

  3. Aerts JM, Groener JE, Kuiper S, et al. Elevated globotriaosylsphingosine is a hallmark of Fabry disease. Proc Natl Acad Sci U S A. 2008;105:2812–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Spada M, Pagliardini S, Yasuda M, et al. High incidence of later-onset Fabry disease revealed by newborn screening. Am J Hum Genet. 2006;79:31–40.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Mehta A, Ricci R, Widmer U, et al. Fabry disease defined: baseline clinical manifestations of 366 patients in the Fabry outcome survey. Eur J Clin Invest. 2004;34:236–42.

    Article  CAS  PubMed  Google Scholar 

  6. Linhart A, Kampmann C, Zamorano JL, et al. Cardiac manifestations of Anderson-Fabry disease: results from the international Fabry outcome survey. Eur Heart J. 2007;28:1228–35.

    Article  PubMed  Google Scholar 

  7. Lidove O, Chauveheid MP, Caillaud C, et al. Aseptic meningitis and ischaemic stroke in Fabry disease. Int J Clin Pract. 2009;63:1663–7.

    Article  CAS  PubMed  Google Scholar 

  8. Löhle M, Hughes D, Milligan A, et al. Clinical prodromes of neurodegeneration in Anderson-Fabry disease. Neurology. 2015;84:1454–64.

    Article  PubMed  PubMed Central  Google Scholar 

  9. Morgan SH, Rudge P, Smith SJ, et al. The neurological complications of Anderson-Fabry disease (alpha-galactosidase A deficiency) – investigation of symptomatic and presymptomatic patients. Q J Med. 1990;75:491–507.

    CAS  PubMed  Google Scholar 

  10. Luciano CA, Russell JW, Banerjee TK, et al. Physiological characterization of neuropathy in Fabry’s disease. Muscle Nerve. 2002;26:622–9.

    Article  PubMed  Google Scholar 

  11. Kocen RS, Thomas PK. Peripheral nerve involvement in Fabry’s disease. Arch Neurol. 1970;22:81–8.

    Article  CAS  PubMed  Google Scholar 

  12. Onishi A, Dyck PJ. Loss of small peripheral sensory neurons in Fabry disease. Histologic and morphometric evaluation of cutaneous nerves, spinal ganglia and posterior columns. Arch Neurol. 1974;31:120–7.

    Article  CAS  PubMed  Google Scholar 

  13. Choi L, Vernon J, Kopach O, et al. The Fabry disease-associated lipid Lyso-Gb3 enhances voltage-gated calcium currents in sensory neurons and causes pain. Neurosci Lett. 2015;594:163–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Mitsias P, Levine SR. Cerebrovascular complications of Fabry’s disease. Ann Neurol. 1996;40:8–17.

    Article  CAS  PubMed  Google Scholar 

  15. MacDermot KD, Holmes A, Miners AH. Anderson-Fabry disease: clinical manifestations and impact of disease in a cohort of 98 hemizygous males. J Med Genet. 2001;38:750–60.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. MacDermot KD, Holmes A, Miners AH. Anderson-Fabry disease: clinical manifestations and impact of disease in a cohort of 60 obligate carrier females. J Med Genet. 2001;38:769–74.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Galanos J, Nicholls K, Grigg L, et al. Clinical features of Fabry disease in Australian patients. Intern Med J. 2002;32:575–84.

    Article  CAS  PubMed  Google Scholar 

  18. Sims K, Politei J, Banikazemi M, et al. Stroke in Fabry disease frequently occurs before diagnosis and in the absence of other clinical events. Natural history data from the Fabry Registry. Stroke. 2009;40:788–94.

    Article  PubMed  Google Scholar 

  19. Deegan PB, Baehner AF, Barba Romero MA, for the European FOS Investigators, et al. Natural history of Fabry disease in females in the Fabry outcome survey. J Med Genet. 2006;43:347–52.

    Article  CAS  PubMed  Google Scholar 

  20. Mehta A, Ginsberg L, for the FOS Investigators. Natural history of the cerebrovascular complications of Fabry disease. Acta Paediatr. 2005;94(Suppl 447):24–7.

    Article  CAS  Google Scholar 

  21. Ginsberg L, Manara R, Reinke J, et al. Characterisation of ischaemic stroke in Fabry disease: data from the international Fabry outcome survey. Eur J Neurol. 2008;15(Suppl 3):21–2.

    Google Scholar 

  22. Fellgiebel A, Müller MJ, Ginsberg L. CNS manifestations of Fabry’s disease. Lancet Neurol. 2006;5:791–5.

    Article  PubMed  Google Scholar 

  23. Ginsberg L, Manara R, Valentine AR, et al. Magnetic resonance imaging changes in Fabry disease. Acta Paediatr. 2006;95(Suppl 451):57–62.

    Article  Google Scholar 

  24. Crutchfield KE, Patronas NJ, Dambrosia JM, et al. Quantitative analysis of cerebral vasculopathy in patients with Fabry disease. Neurology. 1998;50:1746–9.

    Article  CAS  PubMed  Google Scholar 

  25. Fellgiebel A, Müller MJ, Mazanek M, et al. White matter lesion severity in male and female patients with Fabry disease. Neurology. 2005;65:600–2.

    Article  CAS  PubMed  Google Scholar 

  26. Cabrera-Salazar MA, O’Rourke E, Charria-Ortiz G, et al. Radiological evidence of early cerebral microvascular disease in young children with Fabry disease. J Pediatr. 2005;147:102–5.

    Article  PubMed  Google Scholar 

  27. Rolfs A, Böttcher T, Zschiesche M, et al. Prevalence of Fabry disease in patients with cryptogenic stroke: a prospective study. Lancet. 2005;366:1794–6.

    Article  PubMed  Google Scholar 

  28. Reisin RC, Romero C, Marchesoni C, et al. Brain MRI findings in patients with Fabry disease. J Neurol Sci. 2011;305:41–4.

    Article  PubMed  Google Scholar 

  29. Kono Y, Wakabayashi T, Kobayashi M, et al. Characteristics of cerebral microbleeds in patients with Fabry disease. J Stroke Cerebrovasc Dis. 2016;25:1320–5.

    Article  PubMed  Google Scholar 

  30. Moore DF, Ye F, Schiffmann R, et al. Increased signal intensity in the pulvinar on T1-weighted images: a pathognomonic MR imaging sign of Fabry disease. AJNR Am J Neuroradiol. 2003;24:1096–101.

    PubMed  Google Scholar 

  31. Takanashi J, Barkovich AJ, Dillon WP, et al. T1 hyperintensity in the pulvinar: key imaging feature for diagnosis of Fabry disease. AJNR Am J Neuroradiol. 2003;24:916–21.

    PubMed  Google Scholar 

  32. Garzuly F, Maródi L, Erdös M, et al. Megadolichobasilar anomaly with thrombosis in a family with Fabry’s disease and a novel mutation in the α-galactosidase A gene. Brain. 2005;128:2078–83.

    Article  PubMed  Google Scholar 

  33. Fellgiebel A, Keller I, Marin D, et al. Diagnostic utility of different MRI and MR angiography measures in Fabry disease. Neurology. 2009;72:63–8.

    Article  CAS  PubMed  Google Scholar 

  34. Fellgiebel A, Keller I, Martus P, et al. Basilar artery diameter is a potential screening tool for Fabry disease in young stroke patients. Cerebrovasc Dis. 2011;31:294–9.

    Article  PubMed  Google Scholar 

  35. Fazekas F, Enzinger C, Schmidt R, et al. Brain magnetic resonance imaging findings fail to suspect Fabry disease in young patients with an acute cerebrovascular event. Stroke. 2015;46:1548–53.

    Article  PubMed  Google Scholar 

  36. Gal A. Molecular genetics of Fabry disease and genotype-phenotype correlation. In: Elstein D, Altarescu G, Beck M, editors. Fabry disease. New York: Springer-Verlag; 2010. p. 3–19.

    Chapter  Google Scholar 

  37. Ginsberg L, Larroque S, Burlina A, et al. Stroke in Fabry disease: genotype-phenotype correlation. J Inherit Metab Dis. 2012;35:S93.

    Google Scholar 

  38. Nakao S, Takenaka T, Maeda M, et al. An atypical variant of Fabry's disease in men with left ventricular hypertrophy. N Engl J Med. 1995;333:288–93.

    Article  CAS  PubMed  Google Scholar 

  39. Ritter M, Dittrich R, Droste DW. Microembolus detection in four patients with Fabry disease: further support for a primarily microangiopathic origin of early cerebrovascular symptoms. Eur Neurol. 2003;50:141–5.

    Article  PubMed  Google Scholar 

  40. Moore DF, Scott LT, Gladwin MT, et al. Regional cerebral hyperperfusion and nitric oxide pathway deregulation in Fabry disease: reversal by enzyme replacement therapy. Circulation. 2001;104:1506–12.

    Article  CAS  PubMed  Google Scholar 

  41. Hilz MJ, Kolodny EH, Brys M, et al. Reduced cerebral blood flow velocity and impaired cerebral autoregulation in patients with Fabry disease. J Neurol. 2004;251:564–70.

    Article  PubMed  Google Scholar 

  42. DeGraba T, Azhar S, Dignat-George F, et al. Profile of endothelial and leukocyte activation in Fabry patients. Ann Neurol. 2000;47:229–33.

    Article  CAS  PubMed  Google Scholar 

  43. Kolodny E, Fellgiebel A, Hilz MJ, et al. Cerebrovascular involvement in Fabry disease: current status of knowledge. Stroke. 2015;46:302–13.

    Article  PubMed  Google Scholar 

  44. Rolfs A, Fazekas F, Grittner U, et al. Acute cerebrovascular disease in the young: the stroke in young Fabry patients study. Stroke. 2013;44:340–9.

    Article  PubMed  Google Scholar 

  45. Linthorst GE, Ginsberg L. Prevalence of Fabry disease in TIA/stroke cohorts. What defines Fabry disease? Eur J Neurol. 2012;19:1383–4.

    Article  CAS  PubMed  Google Scholar 

  46. van der Tol L, Smid BE, Poorthuis BJ, et al. A systematic review on screening for Fabry disease: prevalence of individuals with genetic variants of unknown significance. J Med Genet. 2014;51:1–9.

    Article  PubMed  Google Scholar 

  47. Saarinen JT, Sillanpää N, Kantola I. A male Fabry disease patient treated with intravenous thrombolysis for acute ischemic stroke. J Clin Neurosci. 2015;22:423–5.

    Article  PubMed  Google Scholar 

  48. Schiffmann R, Kopp JB, Austin 3rd HA, et al. Enzyme replacement therapy in Fabry disease: a randomized controlled trial. JAMA. 2001;285:2743–9.

    Article  CAS  PubMed  Google Scholar 

  49. Eng CM, Guffon N, Wilcox WR, for the International Collaborative Fabry Disease Study Group, et al. Safety and efficacy of recombinant human α-galactosidase A replacement therapy in Fabry’s disease. N Engl J Med. 2001;345:9–16.

    Article  CAS  PubMed  Google Scholar 

  50. Schiffmann R, Floeter MK, Dambrosia JM, et al. Enzyme replacement therapy improves peripheral nerve and sweat function in Fabry disease. Muscle Nerve. 2003;28:703–10.

    Article  CAS  PubMed  Google Scholar 

  51. Hajioff D, Enever Y, Quiney R, et al. Hearing loss in Fabry disease: the effect of agalsidase alfa replacement therapy. J Inherit Metab Dis. 2003;26:787–94.

    Article  CAS  PubMed  Google Scholar 

  52. Mehta A, Beck M, Elliott P, for the Fabry Outcome Survey Investigators, et al. Enzyme replacement therapy with agalsidase alfa in patients with Fabry’s disease: an analysis of registry data. Lancet. 2009;374:1986–96.

    Article  CAS  PubMed  Google Scholar 

  53. Germain DP, Charrow J, Desnick RJ, et al. Ten-year outcome of enzyme replacement therapy with agalsidase beta in patients with Fabry disease. J Med Genet. 2015;52:353–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  54. Rombach SM, Smid BE, Bouwman MG, et al. Long term enzyme replacement therapy for Fabry disease: effectiveness on kidney, heart and brain. Orphanet J Rare Dis. 2013;8:47.

    Article  PubMed  PubMed Central  Google Scholar 

  55. Fellgiebel A, Gartenschläger M, Wildberger K, et al. Enzyme replacement therapy stabilized white matter lesion progression in Fabry disease. Cerebrovasc Dis. 2014;38:448–56.

    Article  CAS  PubMed  Google Scholar 

  56. Schiffmann R, Rapkiewicz A, Abu-Asab M, et al. Pathological findings in a patient with Fabry disease who died after 2.5 years of enzyme replacement. Virchows Arch. 2005;29:1–7.

    Google Scholar 

  57. Biegstraaten M, Arngrimsson R, Barbey F, et al. Recommendations for initiation and cessation of enzyme replacement therapy in patients with Fabry disease: the European Fabry Working Group consensus document. Orphanet J Rare Dis. 2015;10:36.

    Article  PubMed  PubMed Central  Google Scholar 

  58. Altarescu G, Moore DF, Schiffmann R. Effect of genetic modifiers on cerebral lesions in Fabry disease. Neurology. 2005;64:2148–50.

    Article  CAS  PubMed  Google Scholar 

  59. Albrecht J, Dellani PR, Müller MJ, et al. Voxel based analyses of diffusion tensor imaging in Fabry disease. J Neurol Neurosurg Psychiatry. 2007;78:964–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  60. Hughes DA, Malmenas M, Deegan PB, et al. Fabry international prognostic index – a predictive severity score for Anderson-Fabry disease. J Med Genet. 2012;49:212–20.

    Article  CAS  PubMed  Google Scholar 

  61. Germain DP, Hughes DA, Nicholls K, et al. Treatment of Fabry’s disease with the pharmacologic chaperone migalastat. N Engl J Med. 2016;375:545–55.

    Article  CAS  PubMed  Google Scholar 

  62. Hughes DA, Nicholls K, Shankar SP, et al. Oral pharmacological chaperone migalastat compared with enzyme replacement therapy in Fabry disease: 18-month results from the randomised phase III ATTRACT study. J Med Genet 2017 (in press).

    Google Scholar 

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Authors and Affiliations

  1. University College London, Medical School, Royal Free Hospital, London, UK

    Lionel Ginsberg BSc.,MBBS.,PhD.,FRCP.,FHEA

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  1. Lionel Ginsberg BSc.,MBBS.,PhD.,FRCP.,FHEA
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Correspondence to Lionel Ginsberg BSc.,MBBS.,PhD.,FRCP.,FHEA .

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Editors and Affiliations

  1. Department of Neurology, Institute of Cardiovascular Research Royal Holloway College, University of London Imperial College London Healthcare NHS Trust, London, United Kingdom

    Pankaj Sharma

  2. Department of Neurology, Mayo Clinic, Jacksonville, Florida, USA

    James F. Meschia

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Ginsberg, L. (2017). Monogenic Disorder: Fabry Disease. In: Sharma, P., Meschia, J. (eds) Stroke Genetics. Springer, Cham. https://doi.org/10.1007/978-3-319-56210-0_7

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  • DOI: https://doi.org/10.1007/978-3-319-56210-0_7

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