Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Review Article
  • Published:

Neurological manifestations in Fabry's disease

Nature Clinical Practice Neurology volume 3, pages 95–106 (2007)Cite this article

Abstract

Fabry's disease is an X-linked lysosomal storage disorder caused by a defect in the gene that encodes the lysosomal enzyme α-galactosidase A. Symptoms arise because of accumulation of globotriaosylceramide in multiple organs, resulting in severely reduced quality of life and premature death. Neurological symptoms, such as burning sensations (occasionally accompanied by acroparesthesia) and stroke, are among the first to appear, and occur in both male and female patients. A delay in establishing the diagnosis of Fabry's disease can cause unnecessary problems, especially now that enzyme replacement treatment is available to prevent irreversible organ damage. Females with Fabry's disease who present with pain have often been ignored and misdiagnosed because of the disorder's X-linked inheritance. This Review will stress the importance of recognizing neurological symptoms for the diagnosis of Fabry's disease. The possible pathophysiological background will also be discussed.

Key Points

  • Fabry's disease is an X-linked inherited disease, with multiorgan symptoms presenting in both male and female patients

  • Male patients with Fabry's disease present from childhood with burning, lancinating pain (sometimes accompanied by acroparesthesia) and hypohidrosis

  • Female patients with Fabry's disease are phenotypically more heterogeneous than are male patients, but can also present with severe symptoms

  • Stroke appears in early life, with male patients presenting at a lower age than female patients, although the frequency is higher among females

  • Misdiagnosis and delays in diagnosis are major problems; it is important for neurologists to consider a diagnosis of Fabry's disease in patients presenting with neuropathic pain and premature idiopathic stroke

  • Enzyme replacement therapy is essential before irreversible organ damage occurs, and supportive therapy is necessary to prevent stroke, to treat neuropathic pain and to increase quality of life

  • Genetic counseling is essential, as is a multidisciplinary approach to managing patients with Fabry's disease

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Figure 1: Possible mechanisms causing neuropathic pain in Fabry's disease.

Similar content being viewed by others

References

  1. Desnick RJ et al. (1995) Fabry disease: alpha-Galactosidase A deficiency. In The Metabolic and Molecular Bases of Inherited Disease, 2741–2784 (Eds Scriver CR et al.) New York: McGraw Hill

    Google Scholar 

  2. Meikle PJ et al. (1999) Prevalence of lysosomal storage disorders. JAMA 281: 249–254

    Article  CAS  PubMed  Google Scholar 

  3. Spada M et al. (2006) High incidence of later-onset fabry disease revealed by newborn screening. Am J Hum Genet 79: 31–40

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Nakao S et al. (2003) Fabry disease: detection of undiagnosed hemodialysis patients and identification of a “renal variant” phenotype. Kidney Int 64: 801–807

    Article  PubMed  Google Scholar 

  5. Rolfs A et al. (2005) Prevalence of Fabry disease in patients with cryptogenic stroke: a prospective study. Lancet 366: 1794–1796

    Article  PubMed  Google Scholar 

  6. Mehta A et al. (2004) Fabry disease defined: baseline clinical manifestations of 366 patients in the Fabry Outcome Survey. Eur J Clin Invest 34: 236–242

    Article  CAS  PubMed  Google Scholar 

  7. Wilcox W and Wanner C (2005) Fabry RADAR 2005. The Fabry Registry Aggregate Data Annual Report 2005

  8. The Human Gene Mutation Database at the Institute of Medical Genetics in Cardiff [http://www.hgmd.org]

  9. Matsuzawa F et al. (2005) Fabry disease: correlation between structural changes in alpha-galactosidase, and clinical and biochemical phenotypes. Hum Genet 117: 317–328

    Article  CAS  PubMed  Google Scholar 

  10. Garman SC and Garboczi DN (2004) The molecular defect leading to Fabry disease: structure of human alpha-galactosidase. J Mol Biol 337: 319–335

    Article  CAS  PubMed  Google Scholar 

  11. Pastores GM and Lien YH (2002) Biochemical and molecular genetic basis of Fabry disease. J Am Soc Nephrol 13 (Suppl 2): S130–S133

    Article  CAS  PubMed  Google Scholar 

  12. Lemansky P et al. (1987) Synthesis and processing of alpha-galactosidase A in human fibroblasts: evidence for different mutations in Fabry disease. J Biol Chem 262: 2062–2065

    CAS  PubMed  Google Scholar 

  13. Cable WJ et al. (1982) Fabry disease: significance of ultrastructural localization of lipid inclusions in dermal nerves. Neurology 32: 347–353

    Article  CAS  PubMed  Google Scholar 

  14. Pellissier JF et al. (1981) Morphological and biochemical changes in muscle and peripheral nerve in Fabry's disease. Muscle Nerve 4: 381–387

    Article  CAS  PubMed  Google Scholar 

  15. Toyooka K and Said G (1997) Nerve biopsy findings in hemizygous and heterozygous patients with Fabry's disease. J Neurol 244: 464–468

    Article  CAS  PubMed  Google Scholar 

  16. Gemignani F et al. (1984) Pathological study of the sural nerve in Fabry's disease. Eur Neurol 23: 173–181

    Article  CAS  PubMed  Google Scholar 

  17. Kaye EM et al. (1988) Nervous system involvement in Fabry's disease: clinicopathological and biochemical correlation. Ann Neurol 23: 505–509

    Article  CAS  PubMed  Google Scholar 

  18. Tabira T et al. (1974) Neuropathological and biochemical studies in Fabry's disease. Acta Neuropathol (Berl) 30: 345–354

    Article  CAS  Google Scholar 

  19. Hozumi I et al. (1989) Accumulation of glycosphingolipids in spinal and sympathetic ganglia of a symptomatic heterozygote of Fabry's disease. J Neurol Sci 90: 273–280

    Article  CAS  PubMed  Google Scholar 

  20. deVeber GA et al. (1992) Fabry disease: immunocytochemical characterization of neuronal involvement. Ann Neurol 31: 409–415

    Article  CAS  PubMed  Google Scholar 

  21. Gadoth N and Sandbank U (1983) Involvement of dorsal root ganglia in Fabry's disease. J Med Genet 20: 309–312

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Sima AA and Robertson DM (1978) Involvement of peripheral nerve and muscle in Fabry's disease: histologic, ultrastructural, and morphometric studies. Arch Neurol 35: 291–301

    Article  CAS  PubMed  Google Scholar 

  23. Navarro C et al. (2006) Fabry disease: an ultrastructural comparative study of skin in hemizygous and heterozygous patients. Acta Neuropathol (Berl) 111: 178–185

    Article  Google Scholar 

  24. Lao LM et al. (1998) The ultrastructural characteristics of eccrine sweat glands in a Fabry disease patient with hypohidrosis. J Dermatol Sci 18: 109–117

    Article  CAS  PubMed  Google Scholar 

  25. Lacomis D et al. (2005) Neuropathy and Fabry's disease. Muscle Nerve 31: 102–107

    Article  PubMed  Google Scholar 

  26. MacDermot KD et al. (2001) Anderson–Fabry disease: clinical manifestations and impact of disease in a cohort of 60 obligate carrier females. J Med Genet 38: 769–775

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Galanos J et al. (2002) Clinical features of Fabry's disease in Australian patients. Intern Med J 32: 575–584

    Article  CAS  PubMed  Google Scholar 

  28. Wendrich K et al. (2001) Neurological manifestation of Fabry disease in females. Contrib Nephrol 136: 241–244

    Article  Google Scholar 

  29. Schaefer E et al. (2005) Genotype and phenotype in Fabry disease: analysis of the Fabry Outcome Survey. Acta Paediatr Suppl 94 (Suppl): S87–S92

    Article  Google Scholar 

  30. Eng CM et al. (1997) Fabry disease: thirty-five mutations in the alpha-galactosidase A gene in patients with classic and variant phenotypes. Mol Med 3: 174–182

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. von Scheidt W et al. (1991) An atypical variant of Fabry's disease with manifestations confined to the myocardium. N Engl J Med 324: 395–399

    Article  CAS  PubMed  Google Scholar 

  32. Elleder M et al. (1990) Cardiocyte storage and hypertrophy as a sole manifestation of Fabry's disease: report on a case simulating hypertrophic non-obstructive cardiomyopathy. Virchows Arch A Pathol Anat Histopathol 417: 449–455

    Article  CAS  PubMed  Google Scholar 

  33. Sachdev B et al. (2002) Prevalence of Anderson–Fabry disease in male patients with late onset hypertrophic cardiomyopathy. Circulation 105: 1407–1411

    Article  CAS  PubMed  Google Scholar 

  34. Brady RO et al. (2001) Enzyme replacement therapy in Fabry disease. J Inherit Metab Dis 24 (Suppl 2): S18–S24

    Article  Google Scholar 

  35. Schiffmann R et al. (2000) Infusion of alpha-galactosidase A reduces tissue globotriaosylceramide storage in patients with Fabry disease. Proc Natl Acad Sci USA 97: 365–370

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Hilz MJ et al. (2004) Enzyme replacement therapy improves function of C-, Adelta-, and Abeta-nerve fibers in Fabry neuropathy. Neurology 62: 1066–1072

    Article  CAS  PubMed  Google Scholar 

  37. Yam GH et al. (2006) Pharmacological chaperone corrects lysosomal storage in Fabry disease caused by trafficking-incompetent variants. Am J Physiol Cell Physiol 290: C1076–C1082

    Article  CAS  PubMed  Google Scholar 

  38. Fan JQ et al. (1999) Accelerated transport and maturation of lysosomal alpha-galactosidase A in Fabry lymphoblasts by an enzyme inhibitor. Nat Med 5: 112–115

    Article  CAS  PubMed  Google Scholar 

  39. Fan JQ and Ishii S (2003) Cell-based screening of active-site specific chaperone for the treatment of Fabry disease. Methods Enzymol 363: 412–420

    Article  CAS  PubMed  Google Scholar 

  40. Mattocks M et al. (2006) Treatment of neutral glycosphingolipid lysosomal storage diseases via inhibition of the ABC drug transporter, MDR1. Cyclosporin A can lower serum and liver globotriaosyl ceramide levels in the Fabry mouse model. FEBS J 273: 2064–2075

    Article  CAS  PubMed  Google Scholar 

  41. Park J et al. (2003) Long-term correction of globotriaosylceramide storage in Fabry mice by recombinant adeno-associated virus-mediated gene transfer. Proc Natl Acad Sci USA 100: 3450–3454

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Ziegler RJ et al. (2004) AAV2 vector harboring a liver-restricted promoter facilitates sustained expression of therapeutic levels of alpha-galactosidase A and the induction of immune tolerance in Fabry mice. Mol Ther 9: 231–240

    Article  CAS  PubMed  Google Scholar 

  43. Crutchfield KE et al. (1998) Quantitative analysis of cerebral vasculopathy in patients with Fabry disease. Neurology 50: 1746–1749

    Article  CAS  PubMed  Google Scholar 

  44. Mitsias P and Levine SR (1996) Cerebrovascular complications of Fabry's disease. Ann Neurol 40: 8–17

    Article  CAS  PubMed  Google Scholar 

  45. Ginsberg L et al. (2006) Magnetic resonance imaging changes in Fabry disease. Acta Paediatr Suppl 95 (Suppl): S57–S62

    Article  Google Scholar 

  46. Moore DF et al. (2001) Selective arterial distribution of cerebral hyperperfusion in Fabry disease. J Neuroimaging 11: 303–307

    Article  CAS  PubMed  Google Scholar 

  47. Altarescu G et al. (2001) Enhanced endothelium-dependent vasodilation in Fabry disease. Stroke 32: 1559–1562

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. Fellgiebel A et al. (2005) White matter lesion severity in male and female patients with Fabry disease. Neurology 65: 600–602

    Article  CAS  PubMed  Google Scholar 

  49. Fellgiebel A et al. (2006) Pattern of microstructural brain tissue alterations in Fabry disease: a diffusion-tensor imaging study. J Neurol 253: 780–787

    Article  PubMed  Google Scholar 

  50. Jardim L et al. (2004) CNS involvement in Fabry disease: clinical and imaging studies before and after 12 months of enzyme replacement therapy. J Inherit Metab Dis 27: 229–240

    Article  CAS  PubMed  Google Scholar 

  51. Kolodny EH and Pastores GM (2006) CNS pathology and vascular/circulatory abnormalities in Fabry disease. Acta Paediatr Suppl 95 (Suppl): S55–S56

    Article  Google Scholar 

  52. Marino S et al. (2006) Diffuse structural and metabolic brain changes in Fabry disease. J Neurol 253: 434–440

    Article  CAS  PubMed  Google Scholar 

  53. Moore DF et al. (2001) Regional cerebral hyperperfusion and nitric oxide pathway dysregulation in Fabry disease: reversal by enzyme replacement therapy. Circulation 104: 1506–1512

    Article  CAS  PubMed  Google Scholar 

  54. Moore DF et al. (2002) Elevated cerebral blood flow velocities in Fabry disease with reversal after enzyme replacement. Stroke 33: 525–531

    Article  PubMed  Google Scholar 

  55. Fellgiebel A et al. (2006) CNS manifestations of Fabry's disease. Lancet Neurol 5: 791–795

    Article  PubMed  Google Scholar 

  56. Bowsher D (1996) Central pain: clinical and physiological characteristics. J Neurol Neurosurg Psychiatry 61: 62–69

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  57. Zimmermann M (2001) Pathobiology of neuropathic pain. Eur J Pharmacol 429: 23–37

    Article  CAS  PubMed  Google Scholar 

  58. Baron R (2006) Mechanisms of disease: neuropathic pain—a clinical perspective. Nat Clin Pract Neurol 2: 95–106

    Article  PubMed  Google Scholar 

  59. Finnerup NB and Jensen TS (2006) Mechanisms of disease: mechanism-based classification of neuropathic pain—a critical analysis. Nat Clin Pract Neurol 2: 107–115

    Article  PubMed  Google Scholar 

  60. Woolf CJ and Salter MW (2000) Neuronal plasticity: increasing the gain in pain. Science 288: 1765–1769

    Article  CAS  PubMed  Google Scholar 

  61. Hasholt L et al. (1990) A Fabry's disease heterozygote with a new mutation: biochemical, ultrastructural, and clinical investigations. J Med Genet 27: 303–306

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  62. Whybra C et al. (2001) Anderson–Fabry disease: clinical manifestations of disease in female heterozygotes. J Inherit Metab Dis 24: 715–724

    Article  CAS  PubMed  Google Scholar 

  63. Deegan PB et al. (2006) Natural history of Fabry disease in females in the Fabry Outcome Survey. J Med Genet 43: 347–352

    Article  CAS  PubMed  Google Scholar 

  64. Hilz MJ et al. (2000) Lower limb cold exposure induces pain and prolonged small fiber dysfunction in Fabry patients. Pain 84: 361–365

    Article  CAS  PubMed  Google Scholar 

  65. Dutsch M et al. (2002) Small fiber dysfunction predominates in Fabry neuropathy. J Clin Neurophysiol 19: 575–586

    Article  CAS  PubMed  Google Scholar 

  66. Luciano CA et al. (2002) Physiological characterization of neuropathy in Fabry's disease. Muscle Nerve 26: 622–629

    Article  PubMed  Google Scholar 

  67. Morgan SH et al. (1990) The neurological complications of Anderson–Fabry disease (alpha-galactosidase A deficiency)—investigation of symptomatic and presymptomatic patients. Q J Med 75: 491–507

    CAS  PubMed  Google Scholar 

  68. Moller AT et al. (2006) Small-fibre neuropathy in female Fabry patients: reduced allodynia and skin blood flow after topical capsaicin. J Peripher Nerv Syst 11: 119–125

    Article  PubMed  Google Scholar 

  69. Filling-Katz MR et al. (1989) Carbamazepine in Fabry's disease: effective analgesia with dose-dependent exacerbation of autonomic dysfunction. Neurology 39: 598–600

    Article  CAS  PubMed  Google Scholar 

  70. Ries M et al. (2003) Use of gabapentin to reduce chronic neuropathic pain in Fabry disease. J Inherit Metab Dis 26: 413–414

    Article  CAS  PubMed  Google Scholar 

  71. Schiffmann R et al. (2003) Enzyme replacement therapy improves peripheral nerve and sweat function in Fabry disease. Muscle Nerve 28: 703–710

    Article  CAS  PubMed  Google Scholar 

  72. Schiffmann R et al. (2006) Enzyme replacement therapy and intraepidermal innervation density in Fabry disease. Muscle Nerve 34: 53–56

    Article  CAS  PubMed  Google Scholar 

  73. Myers RR et al. (2006) The role of neuroinflammation in neuropathic pain: mechanisms and therapeutic targets. Drug Discov Today 11: 8–20

    Article  CAS  PubMed  Google Scholar 

  74. Jensen TS and Baron R (2003) Translation of symptoms and signs into mechanisms in neuropathic pain. Pain 102: 1–8

    Article  PubMed  Google Scholar 

  75. Jensen TS et al. (2001) The clinical picture of neuropathic pain. Eur J Pharmacol 429: 1–11

    Article  CAS  PubMed  Google Scholar 

  76. Newton RA et al. (2001) Dorsal root ganglion neurons show increased expression of the calcium channel alpha2delta-1 subunit following partial sciatic nerve injury. Brain Res Mol Brain Res 95: 1–8

    Article  CAS  PubMed  Google Scholar 

  77. Luo ZD et al. (2002) Injury type-specific calcium channel alpha 2 delta-1 subunit up-regulation in rat neuropathic pain models correlates with antiallodynic effects of gabapentin. J Pharmacol Exp Ther 303: 1199–1205

    Article  CAS  PubMed  Google Scholar 

  78. Wood JN et al. (2004) Voltage-gated sodium channels and pain pathways. J Neurobiol 61: 55–71

    Article  CAS  PubMed  Google Scholar 

  79. DeGraba T et al. (2000) Profile of endothelial and leukocyte activation in Fabry patients. Ann Neurol 47: 229–233

    Article  CAS  PubMed  Google Scholar 

  80. Kalliokoski RJ et al. (2006) Structural and functional changes in peripheral vasculature of Fabry patients. J Inherit Metab Dis 29: 660–666

    Article  PubMed  Google Scholar 

  81. Boutouyrie P et al. (2001) Non-invasive evaluation of arterial involvement in patients affected with Fabry disease. J Med Genet 38: 629–631

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  82. Bots ML et al. (1993) Carotid intima-media wall thickness in elderly women with and without atherosclerosis of the abdominal aorta. Atherosclerosis 102: 99–105

    Article  CAS  PubMed  Google Scholar 

  83. Barbey F et al. (2006) Increased carotid intima–media thickness in the absence of atherosclerotic plaques in an adult population with Fabry disease. Acta Paediatr Suppl 95 (Suppl): S63–S68

    Article  Google Scholar 

  84. Schiffmann R et al. (2006) Pathological findings in a patient with Fabry disease who died after 2.5 years of enzyme replacement. Virchows Arch 448: 337–343

    Article  PubMed  Google Scholar 

  85. Bodary PF et al. (2005) Alpha-galactosidase A deficiency accelerates atherosclerosis in mice with apolipoprotein E deficiency. Circulation 111: 629–632

    Article  CAS  PubMed  Google Scholar 

  86. Inagaki M et al. (1992) Relative hypoxia of the extremities in Fabry disease. Brain Dev 14: 328–333

    Article  CAS  PubMed  Google Scholar 

  87. Demuth K and Germain DP (2002) Endothelial markers and homocysteine in patients with classic Fabry disease. Acta Paediatr Suppl 91 (Suppl): S57–S61

    Article  Google Scholar 

  88. Lang PM et al. (2006) Sensory neuropathy and signs of central sensitization in patients with peripheral arterial disease. Pain 124: 190–200

    Article  PubMed  Google Scholar 

  89. Birklein F et al. (2000) Experimental tissue acidosis leads to increased pain in complex regional pain syndrome (CRPS). Pain 87: 227–234

    Article  CAS  PubMed  Google Scholar 

  90. Fujimura H et al. (1991) Vulnerability of nerve fibres to ischaemia: a quantitative light and electron microscope study. Brain 114: 1929–1942

    Article  PubMed  Google Scholar 

  91. Bevan S and Geppetti P (1994) Protons: small stimulants of capsaicin-sensitive sensory nerves. Trends Neurosci 17: 509–512

    Article  CAS  PubMed  Google Scholar 

  92. Fu D et al. (2004) Permanent occlusion of the middle cerebral artery upregulates expression of cytokines and neuronal nitric oxide synthase in the spinal cord and urinary bladder in the adult rat. Neuroscience 125: 819–831

    Article  CAS  PubMed  Google Scholar 

  93. Sommer C and Kress M (2004) Recent findings on how proinflammatory cytokines cause pain: peripheral mechanisms in inflammatory and neuropathic hyperalgesia. Neurosci Lett 361: 184–187

    Article  CAS  PubMed  Google Scholar 

  94. Breese NM et al. (2005) Peripheral inflammation selectively increases TRPV1 function in IB4-positive sensory neurons from adult mouse. Pain 115: 37–49

    Article  CAS  PubMed  Google Scholar 

  95. Schafers M et al. (2002) Anterograde transport of tumor necrosis factor-alpha in the intact and injured rat sciatic nerve. J Neurosci 22: 536–545

    Article  PubMed  PubMed Central  Google Scholar 

  96. Seino Y et al. (1983) Peripheral hemodynamics in patients with Fabry's disease. Am Heart J 105: 783–787

    Article  CAS  PubMed  Google Scholar 

  97. Lyon MF (2002) X-chromosome inactivation and human genetic disease. Acta Paediatr Suppl 91 (Suppl): S107–S112

    Article  Google Scholar 

  98. Migeon BR and Haisley-Royster C (1998) Familial skewed X inactivation and X-linked mutations: unbalanced X inactivation is a powerful means to ascertain X-linked genes that affect cell proliferation. Am J Hum Genet 62: 1555–1557

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  99. Van den Veyver I (2001) Skewed X inactivation in X-linked disorders. Semin Reprod Med 19: 183–191

    Article  CAS  PubMed  Google Scholar 

  100. Puck JM and Willard HF (1998) X inactivation in females with X-linked disease. N Engl J Med 338: 325–328

    Article  CAS  PubMed  Google Scholar 

  101. Dobyns WB (2006) The pattern of inheritance of X-linked traits is not dominant or recessive, just X-linked. Acta Paediatr Suppl 95 (Suppl): S11–S15

    Article  Google Scholar 

  102. Redonnet-Vernhet I et al. (1996) Uneven X inactivation in a female monozygotic twin pair with Fabry disease and discordant expression of a novel mutation in the alpha-galactosidase A gene. J Med Genet 33: 682–688

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  103. Dobrovolny R et al. (2005) Relationship between X-inactivation and clinical involvement in Fabry heterozygotes: eleven novel mutations in the alpha-galactosidase A gene in the Czech and Slovak population. J Mol Med 83: 647–654

    Article  CAS  PubMed  Google Scholar 

  104. Morrone A et al. (2003) Fabry disease: molecular studies in Italian patients and X inactivation analysis in manifesting carriers. J Med Genet 40: e103

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  105. Maier EM et al. (2006) Disease manifestations and X inactivation in heterozygous females with Fabry disease. Acta Paediatr Suppl 95 (Suppl): S30–S38

    Article  Google Scholar 

  106. Beck M (2006) The Mainz Severity Score Index (MSSI): development and validation of a system for scoring the signs and symptoms of Fabry disease. Acta Paediatr Suppl 95 (Suppl): S43–S46

    Article  Google Scholar 

  107. Linthorst GE et al. (2003) Blood group does not correlate with disease severity in patients with Fabry disease (alpha-galactosidase A deficiency). Blood Cells Mol Dis 31: 324–326

    Article  CAS  PubMed  Google Scholar 

  108. Street NJ et al. (2006) Comparison of health-related quality of life between heterozygous women with Fabry disease, a healthy control population, and patients with other chronic disease. Genet Med 8: 346–353

    Article  PubMed  Google Scholar 

  109. MacDermot KD et al. (2001) Anderson–Fabry disease: clinical manifestations and impact of disease in a cohort of 98 hemizygous males. J Med Genet 38: 750–760

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  110. Gupta S et al. (2005) The relationship of vascular glycolipid storage to clinical manifestations of Fabry disease: a cross-sectional study of a large cohort of clinically affected heterozygous women. Medicine (Baltimore) 84: 261–268

    Article  CAS  Google Scholar 

  111. Guffon N (2003) Clinical presentation in female patients with Fabry disease. J Med Genet 40: e38

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  112. Shabbeer J et al. (2006) Fabry disease: identification of 50 novel alpha-galactosidase A mutations causing the classic phenotype and three-dimensional structural analysis of 29 missense mutations. Hum Genomics 2: 297–309

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  113. MacDermot KD et al. (2001) Natural history of Fabry disease in affected males and obligate carrier females. J Inherit Metab Dis 24 (Suppl 2): S13–S14

    Article  Google Scholar 

  114. Scott LJ et al. (1999) Quantitative analysis of epidermal innervation in Fabry disease. Neurology 52: 1249–1254

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. AT Møller is an MD and PhD student at the Danish Pain Research Center, and TS Jensen is a Consultant in Neurology and Professor of Experimental and Clinical Pain Research, both at the Aarhus University Hospital, Aarhus, Denmark.,

    Anette T Møller & Troels S Jensen

Authors
  1. Anette T Møller
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Troels S Jensen
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Anette T Møller.

Ethics declarations

Competing interests

The authors declare no competing financial interests.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Møller, A., Jensen, T. Neurological manifestations in Fabry's disease. Nat Rev Neurol 3, 95–106 (2007). https://doi.org/10.1038/ncpneuro0407

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1038/ncpneuro0407

This article is cited by

Search

Advanced search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing