Neurological features of Fabry disease: Clinical, pathophysiological aspects and therapy

Acta Neurologica Scandinavica

Volumn 126, Issue 2, 2012, Pages 77-97

  Bersano, A ^a   Lanfranconi, S ^b   Valcarenghi, C ^b   Bresolin, N ^b   Micieli, G ^a   Baron, P ^b  

^a C MONDINO NATIONAL NEUROLOGICAL INSTITUTE   (Italy)

^b UNIVERSITY OF MILAN   (Italy)

Author keywords

Enzyme replacement therapy; Fabry disease; Neurological aspects; Neuropathy; Stroke

Indexed keywords

ACETAZOLAMIDE; ALGASIDASE ALPHA; ALGASIDASE BETA; CARBAMAZEPINE; GABAPENTIN; PLACEBO; RECOMBINANT ENZYME; UNCLASSIFIED DRUG;

AUTONOMIC DYSFUNCTION; CEREBROVASCULAR DISEASE; CLINICAL TRIAL; ENZYME REPLACEMENT; FABRY DISEASE; HEARING LOSS; HUMAN; NEUROLOGIC DISEASE; NEUROPATHIC PAIN; NEUROPATHY; NONHUMAN; PATHOPHYSIOLOGY; PERIPHERAL NERVOUS SYSTEM; REVIEW;

ALPHA-GALACTOSIDASE; CEREBROVASCULAR DISORDERS; DIAGNOSIS, DIFFERENTIAL; ENZYME REPLACEMENT THERAPY; FABRY DISEASE; HUMANS; PERIPHERAL NERVOUS SYSTEM DISEASES;

EID: 84863452623     PISSN: 00016314     EISSN: 16000404     Source Type: Journal    
DOI: 10.1111/j.1600-0404.2012.01661.x     Document Type: Review

References (136)

1. Brady RO. Enzymatic abnormalities in diseases of sphingolipid metabolism. Clin Chem 1967;13:756577.
2. Brady RO, Gal AE, Bradley RM, Martensson E, Warshaw AL, Laster L. Enzymatic defect in Fabry disease ceramidetrihexosidase deficiency. N Engl J Med 1967;276:11637.
3. Pastores GM, Lien YH. Biochemical and molecular genetic basis of Fabry disease. J Am Soc Nephrol 2002;13:S1303.
4. Schäfer E, Baron K, Widmer U, Deegan P, Neumann HP, SunderPlassmann G et al. Thirtyfour novel mutations of the GLA gene in 121 patients with Fabry disease. Hum Mutat 2005;25:412.
5. MacDermot KD, Holmes A, Miners AH. AndersonFabry disease: clinical manifestations and impact of disease in a cohort of 60 obligate carrier females. J Med Genet 2001;38:769771.
6. Wendrich K, Whybra C, Ries M, Gal A, Beck M. Neurological manifestation of Fabry disease in females. Contrib Nephrol 2001;136:241244.
7. Hoffmann B, Mayatepek E. Fabry diseaseoften seen, rarely diagnosed. Dtsch Arztebl Int 2009;106:4407.
8. Meikle PJ, Hopwood JJ, Clague AE, Carey WF. Prevalence of lysosomal storage disorders. JAMA 1999;281:24954.
9. Spada M, Pagliardini S, Yasuda M, Tukel T, Thiagarajan G, Sakuraba H et al. High incidence of lateronset Fabry disease revealed by newborn screening. Am J Hum Genet 2006;79:3140.
10. Zarate YA, Hopkin RJ. Fabry's disease. Lancet 2008;372:142735.
11. Rolfs A, Böttcher T, Zschiesche M, Morris P, Winchester B, Bauer P et al. Prevalence of Fabry disease in patients with cryptogenic stroke: a prospective study. Lancet 2005;366:17946.
12. Baptista MV, Ferreira S, PinhoEMelo T et al.; PORTuguese Young STROKE Investigators. Mutations of the GLA gene in young patients with stroke: the PORTYSTROKE studyscreening genetic conditions in Portuguese young stroke patients. Stroke 2010;41:4316.
13. Wozniak MA, Kittner SJ, Tuhrim S et al. Frequency of unrecognized Fabry disease among young EuropeanAmerican and AfricanAmerican men with first ischemic stroke. Stroke 2010;41:7881.
14. Mitsias P, Levine SR. Cerebrovascular complications of Fabry disease. Ann Neurol 1996;40:817.
15. Sims K, Politei J, Banikazemi M, Lee P. 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;40:78894.
16. Grewal RP. Stroke in Fabry disease. J Neurol 1994;241:1536.
17. Mehta A, Ginsberg L; FOS Investigators. Natural history of the cerebrovascular complications of Fabry disease. Acta Paediatr 2005;94:247.
18. Vedder AC, Linthorst GE, van Breemen MJ, Groener JE, Bemelman FJ, Strijland A et al. The Dutch Fabry cohort: diversity of clinical manifestations and Gb3 levels. J Inherit Metab Dis 2007;30:6878.
19. Gupta S, Ries M, Kotsopoulos S, Schiffmann R. The relationship of vascular glycolipid storage to clinical manifestations of Fabry disease: a crosssectional study of a large cohort of clinically affected heterozygous women. Medicine (Baltimore) 2005;84:261268.
20. Kolodny EH, Pastores GM. AndersonFabry disease: extrarenal, neurologic manifestations. J Am Soc Nephrol 2002;13:S3150.
21. Crutchfield KE, Patronas NJ, Dambrosia JM, Frei KP, Banerjee TK, Barton NW et al. Quantitative analysis of cerebral vasculopathy in patients with Fabry disease. Neurology 1998;50:17469.
22. Rolfs A, Martus P, Heuschmann PU et al.; sifap1 Investigators. Protocol and methodology of the Stroke in Young Fabry Patients (sifap1) study: a prospective multicenter European study of 5, 024 young stroke patients aged 1855 years. Cerebrovasc Dis 2011;31:25362.
23. Uusimaa J, Moilanen JS, Vainionpää L et al. Prevalence, segregation, and phenotype of the mitochondrial DNA 3243A>G mutation in children. Ann Neurol 2007;62:27887.
24. Sproule DM, Kaufmann P. Mitochondrial encephalopathy, lactic acidosis, and stroke like episodes: basic concepts, clinical phenotype, and therapeutic management of MELAS syndrome. Ann N Y Acad Sci 2008;1142:13358.
25. Choi EJ, Choi CG, Kim JS. Large cerebral artery involvement in CADASIL. Neurology 2005;65:13224.
26. Choi JC, Kang SY, Kang JH, Park JK. Intracerebral hemorrhages in CADASIL. Neurology 2006;67:20424.
27. Schermuly I, Müller MJ, Keller I et al. Neuropsychiatric symptoms, disease burden and brain structure in Fabry disease. Proceedings of the 5th Symposium on Lysosomal Storage Disorders 2008; Abstract P31, P42.
28. Chabriat H, Joutel A, Dichgans M, TournierLasserve E, Bousser MG. Cadasil. Lancet Neurol 2009;8:64353.
29. Kang SY, Oh JH, Kang JH, Choi JC, Lee JS. Nerve conduction studies in cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy. J Neurol 2009;256:17247.
30. Grand MG, Kaine J, Fulling K et al. Cerebroretinal vasculopathy. Ophthalmology 1988;95:649659.
31. Jen J, Cohen AH, Yue Q et al. Hereditary endotheliopathy with retinopathy, nephropathy, and stroke (HERNS). Neurology 1997;49:32230.
32. Le Charpentier Y, Crouzet J, Le Charpentier M et al. Fabry disease without cutaneous angiokeratoma: diagnosis by electron microscope study of skin biopsy. Sem Hop 1981;57:7882.
33. 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;50:1415.
34. Testai FD, Gorelick PB. Inherited metabolic disorders and stroke part 1: Fabry disease and mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke like episodes. Arch Neurol 2010;67:1924.
35. Rombach SM, Twickler TB, Aerts JM, Linthorst GE, Wijburg FA, Hollak CE. Vasculopathy in patients with Fabry disease: current controversies and research directions. Mol Genet Metab 2010;99:99108.
36. Aerts JM, Groener JE, Kuiper S, DonkerKoopman WE, Strijland A, Ottenhoff R et al. Elevated globotriaosylsphingosine is a hallmark of Fabry disease. Proc Natl Acad Sci USA 2008;105:28127.
37. Eitzman DT, Bodary PF, Shen Y, Khairallah CG, Wild SR, Abe A et al. Fabry disease in mice is associated with agedependent susceptibility to vascular thrombosis. J Am Soc Nephrol 2003;14:298302.
38. Shu L, Murphy HS, Cooling L, Shayman JA. An in vitro model of Fabry disease. J Am Soc Nephrol 2005;16:263645.
39. Shen Y, Bodary PF, Vargas FB, Homeister JW, Gordon D, Ostenso KA et al. Alphagalactosidase A deficiency leads to increased tissue fibrin deposition and thrombosis in mice homozygous for the factor V Leiden mutation. Stroke 2006;37:11068.
40. Utsumi K, Yamamoto N, Kase R et al. High incidence of thrombosis in Fabry disease. Intern Med 1996;36:327329.
41. Moore DF, Gelderman MP, Fuhrmann SR, Schiffmann R, Brady RO, Goldin E. Fabry disease and vascular risk factors: future strategies for patientbased studies and the knockout murine model. Acta Paediatr Suppl 2006;95:6971.
42. Park JL, Whitesall SE, D'Alecy LG, Shu L, Shayman JA. Vascular dysfunction in the alphagalactosidase Aknockout mouse is an endothelial cell, plasma membranebased defect. Clin Exp Pharmacol Physiol 2008;35:115663.
43. Puccio D, Coppola G, Corrado E, Muratori I, Pistone G, Buongiorno MR et al. Non invasive evaluation of endothelial function in patients with AndersonFabry disease. Int Angiol 2005;24:2959.
44. Kalliokoski RJ, Kalliokoski KK, Penttinen M, Kantola I, Leino A, Viikari JS et al. Structural and functional changes in peripheral vasculature of Fabry patients. J Inherit Metab Dis 2006;29:6606.
45. DeGraba T, Azhar S, DignatGeorge F et al. Profile of endothelial and leukocyte activation in Fabry patients. Ann Neurol 2000;47:22933.
46. Moore DF, Scott LT, Gladwin MT, Altarescu G, Kaneski C, Suzuki K et al. Regional cerebral hyperperfusion and nitric oxide pathway dysregulation in Fabry disease: reversal by enzyme replacement therapy. Circulation 2001;104:150612.
47. Heare T, Alp NJ, Priestman DA, Kulkarni AB, Qasba P, Butters TD et al. Severe endothelial dysfunction in the aorta of a mouse model of Fabry disease, partial prevention by Nbutyldeoxynojirimycin treatment. J Inherit Metab Dis. 2007;30:7987.
48. Bodary PF, Shen Y, Vargas FB, Bi X, Ostenso KA, Gu S et al. Alphagalactosidase A deficiency accelerates atherosclerosis in mice with apolipoprotein E deficiency. Circulation 2005;111:62932.
49. Demuth K, Germain DP. Endothelial markers and homocysteine in patients with classic Fabry disease. Acta Paediatr Suppl 2002;91:5761.
50. Garzuly F, Marodi L, Erdos M, Grubits J, Varga Z, Gelpi E et al. Megadolichobasilar anomaly with thrombosis in a family with Fabry disease and a novel mutation in the alphagalactosidase A gene. Brain 2005;128:207883.
51. Utsumi K, Ueda K, Watanabe M et al. Thrombosis in Japanese patients with Fabry disease. J Neurol Sci 2009;283:835.
52. Fellgiebel A, Keller I, Marin D et al. Diagnostic utility of different MRI and MR angiography measures in Fabry disease. Neurology 2009;72:6368.
53. Moore DF, Kaneski CR, Askari H, Schiffmann R. The cerebral vasculopathy of Fabry disease. J Neurol Sci 2007;257:258263.
54. Hilz MJ, Kolodny EH, Brys M, Stemper B, Haendl T, Marthol H. Reduced cerebral blood flow velocity and impaired cerebral autoregulation in patients with Fabry disease. J Neurol 2004;251:56470.
55. Altarescu G, Moore DF, Schiffmann R. Effect of genetic modifiers on cerebral lesions in Fabry disease. Neurology 2005;64:21482150.
56. Fellgiebel A, Müller MJ, Ginsberg L. CNS manifestations of Fabry disease. Lancet Neurol 2005;5:7915.
57. Jardim L, Vedolin L, Schwartz IV, Burin MG, Cecchin C, Kalakun L et al. CNS involvement in Fabry disease: clinical and imaging studies before and after 12 months of enzyme replacement therapy. J Inherit Metab Dis 2004;27:22940.
58. Moore DF, Ye F, Schiffmann R, Butman JA. Increased signal intensity in the pulvinar on T1weighted images: a pathognomonic MR imaging sign of Fabry disease. AJNR Am J Neuroradiol 2003;24:1096101.
59. Takanashi J, Barkovich AJ, Dillon WP, Sherr EH, Hart KA, Packman S. T1 hyperintensity in the pulvinar: key imaging feature for diagnosis of Fabry disease. AJNR Am J Neuroradiol 2003;24:91621.
60. Schiffmann R. Natural history of Fabry disease in males: preliminary observations. J Inherit Metab Dis 2001;24:157.
61. Kocen RS, Thomas PK. Peripheral nerve involvement in Fabry's disease. Arch Neurol 1970;22:818.
62. Ramaswami U, Whybra C, Parini R, PintosMorell G, Mehta A, SunderPlassmann G et al. Clinical manifestations of Fabry disease in children: data from the Fabry Outcome Survey. Acta Paediatr 2006;95:8692.
63. Moller AT, FeldtRasmussen U, Rasmussen AK, Sommer C, Hasholt L, Bach FW et al. Smallfibre neuropathy in female Fabry patients: reduced allodynia and skin blood flow after topical capsaicin. J Peripher Nerv Syst 2006;11:11925.
64. Sheth KJ, Bernhard GC. The arthropathy of Fabry disease. Arthritis Rheum 1979;22:7813.
65. Rahman AN, Simeone FA, Hackel DB, Hall PW, Hirsch EZ, Harris JW. Angiokeratoma corporis diffusum universale (hereditary dystopic lipidosis). Trans Assoc Am Physicians 1971;74:36677.
66. Whybra C, Wendrich K, Ries M, Gal A, Beck M. Clinical manifestation in female Fabry disease patients. Contrib Nephrol 2001;136:24550.
67. Grewal RP. Psychiatric disorders in patients with Fabry disease. Int J Psychiatry Med 1993;23:30712.
68. Dütsch M, Marthol H, Stemper B, Brys M, Haendl T, Hilz MJ. Small fiber dysfunction predominates in Fabry neuropathy. J Clin Neurophysiol 2003;19:57586.
69. Hilz MJ, Stemper B, Kolodny EH. Lower limb cold exposure induces pain and prolonged small fiber dysfunction in Fabry patients. Pain 2000;84:3615.
70. Luciano CA, Russell JW, Banerjee TK, Quirk JM, Scott LJ, Dambrosia JM et al. Physiological characterization of neuropathy in Fabry disease. Muscle Nerve 2002;26:6229.
71. 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;31:1207.
72. Toyooka K, Said G. Nerve biopsy findings in hemizygous and heterozygous patients with Fabry's disease. J Neurol 1997;244:4648.
73. Gadoth N, Sandbank U. Involvement of dorsal root ganglia in Fabry disease. J Med Genet 1983;20:30912.
74. Attal N, Bouhassira D. Mechanisms of pain in peripheral neuropathy. Acta Neurol Scand 1999;173:1224.
75. Schiffmann R. Neuropathy and Fabry disease: pathogenesis and enzyme replacement therapy. Acta Neurol Belg 2006;106:615.
76. Dougherty JA, Rhoney DH. Gabapentin: a unique antiepileptic agent. Neurol Res 2001;23:8219.
77. FillingKatz MR, Merrick HF, Fink JK, Miles RB, Sokol J, Barton NW. Carbamazepine in Fabry disease: effective analgesia with dosedependent exacerbation of autonomic dysfunction. Neurology 1989;39:598600.
78. Freeman R. Autonomic peripheral neuropathy. Lancet 2005;365:125970.
79. Adams D. Hereditary and acquired amyloid neuropathies. J Neurol 2001;248:64757.
80. Houlden H, Smith S, de Carvalho M, Blake J, Mathias C, Wood NW et al. Clinical and genetic characterization of families with triple A (Allgrove) syndrome. Brain 2002;125:268190.
81. Low PA, Dyck PJ, Okazaki H, Kyle R, Fealey RD. The splanchnic autonomic outflow in amyloid neuropathy and Tangier disease. Neurology 1981;31:46163.
82. Schippling S, Orth M, Beisiegel U et al. Severe Tangier disease with a novel ABCA1 gene mutation. Neurology 2008;71:14545.
83. Dyck PJ, Carney JA, Sizemore GW, Okazaki H, Brimijoin WS, Lambert EH. Multiple endocrine neoplasia, type 2b: phenotype recognition, neurological features and their pathological basis. Ann Neurol 1979;6:30214.
84. Johnsen SD, Johnson PC, Stein SR. Familial sensory autonomic neuropathy with arthropathy in Navajo children. Neurology 1993;43:112025.
85. Cable WJ, Kolodny EH, Adams RD. Fabry disease: impaired autonomic function. Neurology 1982;32:498502.
86. MacDermot KD, Holmes A, Miners AH. AndersonFabry disease: clinical manifestations and impact of disease in a cohort of 98 hemizygous males. J Med Genet 2001;38:75060.
87. Low PA, OpferGehrking TL. The autonomic laboratory. Am J Electroneurodiagnostic Technol 1999;39:6576.
88. Yamamoto K, Sobue G, Iwase S, Kumazawa K, Mitsuma T, Mano T. Possible mechanism of anydrosis in a symptomatic female carrier of Fabry disease: an assessment by skin sympathetic nerve activity and sympathetic skin response. Clin Auton Res 1996;6:10710.
89. Lien YH, Lai LW, Lui CY. Unexpected diagnosis of Fabry disease in an 80yearold man with syncope. Cardiology 2001;96:1156.
90. Palla A, Hegemann S, Widmer U, Straumann D. Vestibular and auditory deficits in Fabry disease and their response to enzyme replacement therapy. J Neurol 2007;254:143342.
91. Linthorst GE, Hollak CE, DonkerKoopman WE, Strijland A, Aerts JM. Enzyme therapy for Fabry disease: neutralizing antibodies toward agalsidase alpha and beta. Kidney Int 2004;66:158995.
92. Schaefer RM, TylkiSzymańska A, Hilz MJ. Enzyme replacement therapy for Fabry disease: a systematic review of available evidence. Drugs 2009;69:2179205.
93. Sakurab H, MurataOhsawa M, Kawashima I, Tajima Y, Kotani M, Ohshima T et al. Comparison of the effects of agalsidase alfa and agalsidase beta on cultured human Fabry fibroblasts and Fabry mice. J Hum Genet 2006;51:1808.
94. Mehta A, West ML, PintosMorell G et al. Therapeutic goals in the treatment of Fabry disease. Genet Med 2010;12:71320.
95. Eng CM, Germain DP, Banikazemi M, Warnock DG, Wanner C, Hopkin RJ et al. Fabry disease: guidelines for the evaluation and management of multiorgan system involvement. Genet Med 2006;8:53948.
96. West M, Nicholls K, Mehta A, Clarke JT, Steiner R, Beck M et al. Agalsidase alfa and kidney dysfunction in Fabry disease. J Am Soc Nephrol 2009;20:11329.
97. Imbriaco M, Pisani A, Spinelli L, Cuocolo A, Messalli G, Capuano E et al. Effects of enzymereplacement therapy in patients with AndersonFabry disease: a prospective longterm cardiac magnetic resonance imaging study. Heart 2009;95:11037.
98. Weidemann F, Niemann M, Breunig F, Herrmann S, Beer M, Störk S et al. Longterm effects of enzyme replacement therapy on fabry cardiomyopathy: evidence for a better outcome with early treatment. Circulation 2009;119:5249.
99. Brady RO, Murray GJ, Moore DF, Schiffmann R. Enzyme replacement therapy in Fabry disease. J Inherit Metab Dis 2001;24:1824.
100. Schiffmann R, Murray GJ, Treco D, Daniel P, SellosMoura M, Myers M et al. Infusion of alphagalactosidase A reduces tissue globotriaosylceramide storage in patients with Fabry disease. Proc Natl Acad Sci USA, 2000;97:36570.
101. Alphadel M, Sirrs S, Alfadhel M, Sirrs S. Enzyme replacement therapy for Fabry disease: some answers but more questions. Ther Clin Risk Manag 2011;7:6982.
102. Mehta A, Beck M, Elliott P et al. Enzyme replacement therapy with agalsidase alfa in patients with Fabry's disease: an analysis of registry data. Lancet 2009;374:19861996.
103. Kleinert J, Dehout F, Schwarting A et al. Prevalence of uncontrolled hypertension in patients with Fabry disease. Am J Hypertens 2006;19:782787.
104. Banikazemi M, Bultas J, Waldek S, Wilcox WR, Whitley CB, McDonald M et al. Agalsidasebeta therapy for advanced Fabry disease: a randomized trial. Ann Intern Med 2007;146:7786.
105. Wilcox WR, Banikazemi M, Guffon N et al.; International Fabry Disease Study Group. Longterm safety and efficacy of enzyme replacement therapy for Fabry disease. Am J Hum Genet 2004;75:6574.
106. Buechner S, Moretti M, Burlina AP et al. Central nervous system involvement in AndersonFabry disease: a clinical and MRI retrospective study. J Neurol Neurosurg Psychiatry 2008;79:12491254.
107. Schiffmann R, Moore DF. Neurological effects of enzyme replacement therapy in Fabry disease. In: Mehta A, Beck M, SunderPlassmann G, eds. Fabry disease: perspectives from 5 years of FOS. Oxford: Oxford PharmaGenesis, 2006; Chapter 39.
108. Salviati A, Burlina AP, Borsini W. Nervous system and Fabry disease, from symptoms to diagnosis: damage evaluation and followup in adult patients, enzyme replacement, and support therapy. Neurol Sci 2010;31:299306.
109. Eng CM, Guffon N, Wilcox WR et al.; International Collaborative Fabry Disease Study Group. Safety and efficacy of recombinant human alphagalactosidase Areplacement therapy in Fabry's disease. N Engl J Med 2001;345:916.
110. Eng CM, Banikazemi M, Gordon RE et al. A phase 1/2 clinical trial of enzyme replacement in fabry disease: pharmacokinetic, substrate clearance, and safety studies. Am J Hum Genet 2001;68:71122.
111. Schiffmann R, Kopp JB, Austin HA III et al. Enzyme replacement therapy in Fabry disease: a randomized controlled trial. JAMA 2001;285:27439.
112. Moore DF, Altarescu G, Herscovitch P, Schiffmann R. Enzyme replacement reverses abnormal cerebrovascular responses in Fabry disease. BMC Neurol 2002;2:4.
113. Moore DF, Altarescu G, Ling GS et al. Elevated cerebral blood flow velocities in Fabry disease with reversal after enzyme replacement. Stroke 2002;33:52531.
114. Guffon N, Fouilhoux A. Clinical benefit in Fabry patients given enzyme replacement therapya case series. J Inherit Metab Dis 2004;27:2217.
115. Beck M, Ricci R, Widmer U et al. Fabry disease: overall effects of agalsidase alfa treatment. Eur J Clin Invest 2004;34:83844.
116. Hilz MJ, Brys M, Marthol H, Stemper B, Dütsch M. Enzyme replacement therapy improves function of C, Adelta, and Abetanerve fibers in Fabry neuropathy. Neurology 2004;62:106672.
117. Eto Y, Ohashi T, Utsunomiya Y et al. Enzyme replacement therapy in Japanese Fabry disease patients: the results of a phase 2 bridging study. J Inherit Metab Dis 2005;28:57583.
118. Hoffmann B, Garcia de Lorenzo A, Mehta A, Beck M, Widmer U, Ricci R; FOS European Investigators. Effects of enzyme replacement therapy on pain and health related quality of life in patients with Fabry disease: data from FOS (Fabry Outcome Survey). J Med Genet 2005;42:24752.
119. Schiffmann R, Hauer P, Freeman B et al. Enzyme replacement therapy and intraepidermal innervation density in Fabry disease. Muscle Nerve 2006;34:536.
120. Ries M, Clarke JT, Whybra C et al. Enzymereplacement therapy with agalsidase alfa in children with Fabry disease. Pediatrics 2006;118:92432.
121. Vedder AC, Linthorst GE, Houge G et al. Treatment of Fabry disease: outcome of a comparative trial with agalsidase alfa or beta at a dose of 0.2 mg/kg. PLoS ONE 2007;2:e598.
122. Hoffmann B, Beck M, SunderPlassmann G, Borsini W, Ricci R, Mehta A. Nature and prevalence of pain in Fabry disease and its response to enzyme replacement therapya retrospective analysis from the Fabry Outcome Survey. Clin J Pain 2007;23:53542.
123. Ramaswami U, Wendt S, PintosMorell G et al. Enzyme replacement therapy with agalsidase alfa in children with Fabry disease. Acta Paediatr 2007;96:1227.
124. PierreLouis B, Kumar A, Frishman WH. Fabry disease: cardiac manifestations and therapeutic options. Cardiol Rev 2009;17:315.
125. Mehta A. Fabry disease whom to treat and when. Clin Ther 2008;30:S434.
126. Wang RY, Lelis A, Mirocha J, Wilcox WR. Heterozygous Fabry women are not just carriers, but have a significant burden of disease and impaired quality of life. Genet Med 2007;9:3445.
127. Jung SC, Han IP, Limaye A et al. Adenoassociated viral vectormediated gene transfer results in longterm enzymatic and functional correction in multiple organs of Fabry mice. Proc Natl Acad Sci USA 2001;98:26762681.
128. Parenti G. Treating lysosomal storage diseases with pharmacological chaperones: from concept to clinics. EMBO Mol Med 2009;1:268279.
129. Park J, Murray GJ, Limaye A et al. Longterm correction of globotriaosylceramide storage in Fabry mice by recombinant adenoassociated virusmediated gene transfer. Proc Natl Acad Sci USA 2003;1006:34503454.
130. Yam GH, Bosshard N, Zuber C, Steinmann B, Roth J. Pharmacological chaperone corrects lysosomal storage in Fabry disease caused by trafficking competent variants. Am J Physiol Cell Physiol 2006;290:C1076C1082.
131. Ishii S, Yoshioka H, Mannen K, Kulkarni AB, Fan JQ. Transgenic mouse expressing human mutant alphagalactosidase A in an endogenous enzyme deficient background: a biochemical animal model for studying activesite specific chaperone therapy for Fabry disease. Biochim Biophys Acta 2004;1690:250257.
132. Politei JM. Can we use statins to prevent stroke in Fabry disease? J Inherit Metab Dis 2009;32:4817.
133. FillingKatz MR, Merrick HF, Fink JK, Miles RB, Sokol J, Barton NW. Carbamazepine in Fabry's disease: effective analgesia with dosedependent exacerbation of autonomic dysfunction. Neurology 1989;39:598600.
134. Ries M, Mengel E, Kutschke G et al. Use of gabapentin to reduce chronic neuropathic pain in Fabry disease. J Inherit Metab Dis 2003;26:413414.
135. Brouns R, Thijs V, Eyskens F et al.; BeFaS Investigators. Belgian Fabry study: prevalence of Fabry disease in a cohort of 1000 young patients with cerebrovascular disease. Stroke 2010;41:8638.
136. Dütsch M, Hilz MJ. Neurological complications in Fabry disease. Rev Med Interne 2010;31:S2435.