Skip to main content

Advertisement

SpringerLink
Log in

Fabry disease: raising awareness of the disease among physicians

  • MEET THE EXPERT
  • Published:
Internal and Emergency Medicine Aims and scope Submit manuscript

Abstract

Fabry disease is an X-linked inherited lysosomal disorder due to dysfunctions of the lysosomal enzyme alpha-galactosidase A, causing insufficient breakdown of glycolipids, which are stored in the eyes, kidneys, autonomic nervous system, skin, vessels and cardiovascular system. Manifestations of Fabry disease include progressive renal and cardiac insufficiency, neuropathic pain, stroke and cerebral disease, skin and gastrointestinal symptoms. Clinical onset usually occurs in childhood, but many severe patients are diagnosed in adulthood. Females may be severely affected as males and both may die prematurely due to stroke, heart disease and renal failure. Enzyme replacement therapy can stabilize or reduce the progression of the disease. There is a need to improve the knowledge of Fabry disease, as an early therapy may prevent complications of the disease. This brief overview aims to raise awareness of the signs and symptoms of Fabry disease and to summarize the effects of treatments.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Desnick RJ, Ioannou YA, Eng CM (2001) Alpha-galactosidase A deficiency: Fabry disease. In: Scriver CR, Beaudet AL, Sly WS, Valle D, Kinzler KE, Vogelstein B (eds) The metabolic and molecular bases of inherited diseases, 8th edn. McGraw-Hill, New York, pp 3733–3774

    Google Scholar 

  2. Mehta A, Ricci R, Widmer U 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  PubMed  CAS  Google Scholar 

  3. Eng CM, Fletcher J, Wilcox WR et al (2007) Fabry disease: baseline medical characteristics of a cohort of 1765 males and females in the Fabry Registry. J Inherit Metab Dis 30:184–192

    Article  PubMed  CAS  Google Scholar 

  4. Wang RY, Lelis A, Mirocha J, Wilcox WR (2007) Heterozygous Fabry women are not just carriers, but have a significant burden of disease and impaired quality of life. Genet Med 9:34–45

    Article  PubMed  CAS  Google Scholar 

  5. Wilcox WR, Oliveira JP, Hopkin RJ et al (2008) Females with Fabry disease frequently have major organ involvement: lessons from the Fabry Registry. Mol Genet Metab 93:112–128

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  7. Kotanko P, Kramar R, Devrnja D et al (2004) Results of a nationwide screening for Anderson-Fabry disease among dialysis patients. J Am Soc Nephrol 15:1323–1329

    Article  PubMed  CAS  Google Scholar 

  8. Rolfs A, Bottcher T, Zschiesche M et al (2005) Prevalence of Fabry disease in patients with cryptogenic stroke: a prospective study. Lancet 366:1794–1796

    Article  PubMed  Google Scholar 

  9. Ashley GA, Shabbeer J, Yasuda M, Eng CM, Desnick RJ (2001) Fabry disease: twenty novel alpha-galactosidase A mutations causing the classical phenotype. J Hum Genet 46:192–196

    Article  PubMed  CAS  Google Scholar 

  10. Nakao S, Kodama C, Takenaka T 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 

  11. Nakao S, Takenaka T, Maeda M et al (1995) An atypical variant of Fabry’s disease in men with left ventricular hypertrophy. N Engl J Med 333:288–293

    Article  PubMed  CAS  Google Scholar 

  12. Zarate YA, Hopkin J (2008) Fabry’s disease. Lancet 372:1427–1435

    Article  PubMed  CAS  Google Scholar 

  13. Low M, Nicholls K, Tubridy N et al (2007) Neurology of Fabry disease. Intern Med J 37:436–447

    Article  PubMed  CAS  Google Scholar 

  14. Desnick RJ, Brady RO (2004) Fabry disease in childhood. J Pediatr 144:S20–S26

    Article  PubMed  Google Scholar 

  15. Allen LE, Cosgrave EM, Kersey JP, Ramaswami U (2010) Fabry disease in children: correlation between ocular manifestations, genotype and systemic clinical severity. Br J Ophthalmol 94:1602–1605

    Article  PubMed  CAS  Google Scholar 

  16. Whybra C, Kampmann C, Krummenauer F et al (2004) The Mainz Severity Score Index: a new instrument for quantifying the Anderson-Fabry disease phenotype and the response of patients to enzyme replacement therapy. Clin Genet 65:299–307

    Article  PubMed  CAS  Google Scholar 

  17. Hegemann S, Hajioff D, Conti G et al (2006) Hearing loss in Fabry disease: data from the Fabry Outcome Survey. Eur J Clin Invest 36:654–662

    Article  PubMed  CAS  Google Scholar 

  18. Pieroni M, Chimenti C, De Cobelli F et al (2006) Fabry’s disease cardiomyopathy: echocardiographic detection of endomyocardial glycosphingolipid compartmentalization. J Am Coll Cardiol 47:1663–1671

    Article  PubMed  Google Scholar 

  19. Linhart A, Kampmann C, Zamorano JL et al (2007) Cardiac manifestations of Anderson-Fabry disease: results from the international Fabry outcome survey. Eur Heart J 28:1228–1235

    Article  PubMed  Google Scholar 

  20. Waldek S, Patel MR, Banikazemi M, Lemay R, Lee P (2009) Life expectancy and cause of death in males and females with Fabry disease: findings from the Fabry Registry. Genet Med 11:790–796

    Article  PubMed  Google Scholar 

  21. Moore DF, Kaneski CR, Askari H, Schiffmann R (2007) The cerebral vasculopathy of Fabry disease. J Neurol Sci 257:258–263

    Article  PubMed  Google Scholar 

  22. Alroy J, Sabnis S, Kopp JB (2002) Renal pathology in Fabry disease. J Am Soc Nephrol 13(s2):134–138

    Google Scholar 

  23. Cole AL, Lee PJ, Hughes DA et al (2007) Depression in adults with Fabry disease: a common and under-diagnosed problem. J Inherit Metab Dis 30:943–951

    Article  PubMed  CAS  Google Scholar 

  24. Mehta A, Beck M, Elliott P, On Behalf of the Fabry Outcome Survey Investigators et al (2009) Enzyme replacement therapy with agalsidase alfa in patients with Fabry’s disease: an analysis of registry data. Lancet 374:1986–1996

    Article  PubMed  CAS  Google Scholar 

  25. Desnick RJ, Brady R, Barranger J et al (2003) Fabry disease, an underrecognized multisystemic disorder: expert recommendations for diagnosis, management, and enzyme replacement therapy. Ann Intern Med 38:338–346

    Google Scholar 

  26. Eng CM, Germain DP, Banikazem M et al (2006) Fabry disease: guidelines for the evaluation and management of multi-organ system involvement. Genet Med 8:539–548

    Article  PubMed  Google Scholar 

  27. Giannini EH, Mehta AB, Hilz MJ et al (2010) A validated disease severity scoring system for Fabry disease. Mol Genet Metab 99:283–290

    Article  PubMed  CAS  Google Scholar 

  28. Hughes DA, Ramaswami U et al (2010) Age adjusting severity scores for Anderson-Fabry disease. Mol Genet Metab 101:219–227

    Article  PubMed  CAS  Google Scholar 

  29. Breunig F, Weidemann F, Strotmann J, Knoll A, Wanner C (2006) Clinical benefit of enzyme replacement therapy in Fabry disease. Kidney Int 69:1216–1221

    Article  PubMed  CAS  Google Scholar 

  30. Hughes DA, Elliott PM, Shah J et al (2008) Effects of enzyme replacement therapy on the cardiomyopathy of Anderson-Fabry disease: a randomized, double-blind, placebo-controlled clinical trial of agalsidase-alfa. Heart 94:153–158

    Article  PubMed  CAS  Google Scholar 

  31. Ramaswami U, Wendt S, Pintos-Morell G et al (2007) Enzyme replacement therapy with agalsidase alfa in children with Fabry disease. Acta Paediatr 96:122–127

    Article  PubMed  CAS  Google Scholar 

  32. Schaefer RM, Tylki-Szymańska A, Hilz MJ (2009) Enzyme replacement therapy for Fabry disease: a systematic review of available evidence. Drugs 69:2179–2205

    Article  PubMed  CAS  Google Scholar 

  33. Keating GM, Simpson D (2007) Agalsidase Beta: a review of its use in the management of Fabry disease. Drugs 67:435–455

    Article  PubMed  CAS  Google Scholar 

  34. Mignani R, Panichi V, Giudicissi A et al (2004) Enzyme replacement therapy with agalsidase beta in kidney transplant patients with Fabry disease: a pilot study. Kidney Int 65:1381–1385

    Article  PubMed  CAS  Google Scholar 

  35. Wraith JE, Tylki-Szymanska A, Guffon N et al (2008) Safety and efficacy of enzyme replacement therapy with agalsidase beta: an international, open-label study in pediatric patients with Fabry disease. J Pediatr 152:563–570

    Article  PubMed  CAS  Google Scholar 

  36. Germain DP, Waldek S, Banikazemi M et al (2007) Sustained, long-term renal stabilization after 54 months of agalsidase beta therapy in patients with Fabry disease. J Am Soc Nephrol 18:1547–1557

    Article  PubMed  CAS  Google Scholar 

  37. Vedder AC, Linthorst GE, Houge G et al (2007) Treatment of Fabry disease: outcome of a comparative trial with agalsidase alfa or beta at a dose of 0.2 mg/kg. PLoS One 2:e598

    Article  PubMed  Google Scholar 

  38. Linthorst GE, Hollak CE, Donker-Koopman WE, Strijland A, Aerts JM (2004) Enzyme therapy for Fabry disease: neutralizing antibodies toward agalsidase alpha and beta. Kidney Int 66:1589–1595

    Article  PubMed  CAS  Google Scholar 

  39. Yam GH, Bosshard N, Zuber C, Steinmann B, Roth J (2006) Pharmacological chaperone corrects lysosomal storage in Fabry disease caused by trafficking-incompetent variants. Am J Physiol Cell Physiol 290:C1076–C1082

    Article  PubMed  CAS  Google Scholar 

  40. Germain DP, Fan JQ (2009) Pharmacological chaperone therapy by active-site specific chaperones in Fabry disease: in vitro and preclinical studies. Int J Clin Pharmacol Therapy 47(Suppl 1):S111–S117

    CAS  Google Scholar 

  41. Abe A, Gregory S, Lee L et al (2000) Reduction of globotriaosylceramide in Fabry disease mice by substrate deprivation. J Clin Invest 105:1563–1571

    Article  PubMed  CAS  Google Scholar 

Download references

Conflict of interest

FC attended meetings sponsored by Genzyme Corp. and Shire Human Genetic Therapies. LB declares that has no conflict of interest.

Author information

Authors and Affiliations

  1. Department of Medicine, Endocrinology, Metabolism and Geriatrics, University of Modena and Reggio Emilia, NOSE U.O. Medicina ad indirizzo metabolico-nutrizionistico, Via Giardini 1355, 41126, Modena, MO, Italy

    Francesca Carubbi & Lisa Bonilauri

Authors
  1. Francesca Carubbi
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Lisa Bonilauri
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Francesca Carubbi.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Carubbi, F., Bonilauri, L. Fabry disease: raising awareness of the disease among physicians. Intern Emerg Med 7 (Suppl 3), 227–231 (2012). https://doi.org/10.1007/s11739-012-0821-x

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11739-012-0821-x

Keywords

Search

Navigation