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Treatment of Fabry disease

Authors
Michael Mauer, MD
Jeffrey B Kopp, MD
Section Editors
Gary C Curhan, MD, ScD
Barbara Murphy, MB, BAO, BCh, FRCPI
Deputy Editor
Albert Q Lam, MD

INTRODUCTION

Fabry disease, also called Anderson-Fabry disease, is the second most prevalent lysosomal storage disorder after Gaucher's disease. It is an X-linked inborn error of the glycosphingolipid metabolic pathway. This results in accumulation of globotriaosylceramide (Gb3) within lysosomes in a wide variety of cells, thereby leading to the protean manifestations of the disease [1,2].

There is no cure for Fabry disease. Recombinant alpha-galactosidase A (alpha-Gal A), the enzyme that is deficient in patients with Fabry disease, and migalastat hydrochloride, an oral pharmacological chaperone that facilitates trafficking of alpha-Gal A to lysosomes, are therapeutic options for eligible individuals. The impact of these therapies on mortality is unknown.

The treatment and prognosis of Fabry disease is presented here. The epidemiology, pathogenesis, clinical manifestations, and diagnosis of this disorder are discussed separately. (See "Clinical features and diagnosis of Fabry disease" and "Clinical features, diagnosis, and management of patients with Fabry disease with cardiac disease" and "Neurologic manifestations of Fabry disease".)

GENERAL APPROACH TO THERAPY

The treatment of patients with Fabry disease primarily focuses upon replacing the missing or deficient enzyme (alpha-galactosidase A, or alpha-Gal A). All classically affected males (ie, with very low or undetectable levels of alpha-Gal A) should receive enzyme replacement therapy (ERT) as soon as the diagnosis is made, regardless of whether or not clinical manifestations are present. Female carriers and atypically affected males (ie, with marginal levels of alpha-Gal A) should receive ERT if clinical manifestations (eg, renal, neurologic, cardiovascular) are present. We also treat patients who have end-stage renal disease (ESRD) with enzyme replacement, as this may reduce cardiovascular and neurologic complications of Fabry disease. Although new approaches are being developed, their role in the treatment of Fabry disease is much less well defined. (See 'Alternatives to ERT' below.)

Patients who develop chronic kidney disease should receive the same monitoring and care as a patient with chronic kidney disease due to a different etiology. (See "Overview of the management of chronic kidney disease in adults".)

                                

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Literature review current through: Nov 2016. | This topic last updated: Thu Oct 20 00:00:00 GMT+00:00 2016.
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References
Top
  1. Germain DP. Fabry disease. Orphanet J Rare Dis 2010; 5:30.
  2. Lidove O, Kaminsky P, Hachulla E, et al. Fabry disease 'The New Great Imposter': results of the French Observatoire in Internal Medicine Departments (FIMeD). Clin Genet 2012; 81:571.
  3. Schiffmann R, Murray GJ, Treco D, et al. Infusion of alpha-galactosidase A reduces tissue globotriaosylceramide storage in patients with Fabry disease. Proc Natl Acad Sci U S A 2000; 97:365.
  4. 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; 68:711.
  5. Schiffmann R, Kopp JB, Austin HA 3rd, et al. Enzyme replacement therapy in Fabry disease: a randomized controlled trial. JAMA 2001; 285:2743.
  6. Eng CM, Guffon N, Wilcox WR, et al. Safety and efficacy of recombinant human alpha-galactosidase A--replacement therapy in Fabry's disease. N Engl J Med 2001; 345:9.
  7. El Dib R, Gomaa H, Carvalho RP, et al. Enzyme replacement therapy for Anderson-Fabry disease. Cochrane Database Syst Rev 2016; 7:CD006663.
  8. Najafian B, Svarstad E, Bostad L, et al. Progressive podocyte injury and globotriaosylceramide (GL-3) accumulation in young patients with Fabry disease. Kidney Int 2011; 79:663.
  9. Ortiz A, Abiose A, Bichet DG, et al. Time to treatment benefit for adult patients with Fabry disease receiving agalsidase β: data from the Fabry Registry. J Med Genet 2016; 53:495.
  10. Hopkin RJ, Jefferies JL, Laney DA, et al. The management and treatment of children with Fabry disease: A United States-based perspective. Mol Genet Metab 2016; 117:104.
  11. Terryn W, Cochat P, Froissart R, et al. Fabry nephropathy: indications for screening and guidance for diagnosis and treatment by the European Renal Best Practice. Nephrol Dial Transplant 2013; 28:505.
  12. Desnick RJ, Brady R, Barranger J, et al. Fabry disease, an under-recognized multisystemic disorder: expert recommendations for diagnosis, management, and enzyme replacement therapy. Ann Intern Med 2003; 138:338.
  13. Mosnier JF, Degott C, Bedrossian J, et al. Recurrence of Fabry's disease in a renal allograft eleven years after successful renal transplantation. Transplantation 1991; 51:759.
  14. Bai HW, Shi BY, Qian YY, et al. Endothelial cell chimerism by fluorescence in situ hybridization in gender mismatched renal allograft biopsies. Chin Med J (Engl) 2007; 120:859.
  15. Lubanda JC, Anijalg E, Bzdúch V, et al. Evaluation of a low dose, after a standard therapeutic dose, of agalsidase beta during enzyme replacement therapy in patients with Fabry disease. Genet Med 2009; 11:256.
  16. Tøndel C, Bostad L, Larsen KK, et al. Agalsidase benefits renal histology in young patients with Fabry disease. J Am Soc Nephrol 2013; 24:137.
  17. Weidemann F, Krämer J, Duning T, et al. Patients with Fabry disease after enzyme replacement therapy dose reduction versus treatment switch. J Am Soc Nephrol 2014; 25:837.
  18. Skrunes R, Svarstad E, Kampevold Larsen K, et al. Reaccumulation of globotriaosylceramide in podocytes after agalsidase dose reduction in young Fabry patients. Nephrol Dial Transplant 2016.
  19. Goker-Alpan O, Gambello MJ, Maegawa GH, et al. Reduction of Plasma Globotriaosylsphingosine Levels After Switching from Agalsidase Alfa to Agalsidase Beta as Enzyme Replacement Therapy for Fabry Disease. JIMD Rep 2016; 25:95.
  20. Wilcox WR, Banikazemi M, Guffon N, et al. Long-term safety and efficacy of enzyme replacement therapy for Fabry disease. Am J Hum Genet 2004; 75:65.
  21. Beck M, Ricci R, Widmer U, et al. Fabry disease: overall effects of agalsidase alfa treatment. Eur J Clin Invest 2004; 34:838.
  22. Linthorst GE, Vedder AC, Ormel EE, et al. Home treatment for Fabry disease: practice guidelines based on 3 years experience in The Netherlands. Nephrol Dial Transplant 2006; 21:355.
  23. Weidemann F, Sommer C, Duning T, et al. Department-related tasks and organ-targeted therapy in Fabry disease: an interdisciplinary challenge. Am J Med 2010; 123:658.e1.
  24. Biegstraaten M, Arngrímsson 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.
  25. Arends M, Linthorst GE, Hollak CE, Biegstraaten M. Discontinuation of enzyme replacement therapy in Fabry disease in the Dutch cohort. Mol Genet Metab 2016; 117:194.
  26. Banikazemi M, Bultas J, Waldek S, et al. Agalsidase-beta therapy for advanced Fabry disease: a randomized trial. Ann Intern Med 2007; 146:77.
  27. Bénichou B, Goyal S, Sung C, et al. A retrospective analysis of the potential impact of IgG antibodies to agalsidase beta on efficacy during enzyme replacement therapy for Fabry disease. Mol Genet Metab 2009; 96:4.
  28. Najafian B, Tøndel C, Svarstad E, et al. One Year of Enzyme Replacement Therapy Reduces Globotriaosylceramide Inclusions in Podocytes in Male Adult Patients with Fabry Disease. PLoS One 2016; 11:e0152812.
  29. Schiffmann R, Ries M, Timmons M, et al. Long-term therapy with agalsidase alfa for Fabry disease: safety and effects on renal function in a home infusion setting. Nephrol Dial Transplant 2006; 21:345.
  30. Schiffmann R, Askari H, Timmons M, et al. Weekly enzyme replacement therapy may slow decline of renal function in patients with Fabry disease who are on long-term biweekly dosing. J Am Soc Nephrol 2007; 18:1576.
  31. West M, Nicholls K, Mehta A, et al. Agalsidase alfa and kidney dysfunction in Fabry disease. J Am Soc Nephrol 2009; 20:1132.
  32. Thurberg BL, Rennke H, Colvin RB, et al. Globotriaosylceramide accumulation in the Fabry kidney is cleared from multiple cell types after enzyme replacement therapy. Kidney Int 2002; 62:1933.
  33. Germain DP, Waldek S, Banikazemi M, et al. Sustained, long-term renal stabilization after 54 months of agalsidase beta therapy in patients with Fabry disease. J Am Soc Nephrol 2007; 18:1547.
  34. 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.
  35. Ries M, Clarke JT, Whybra C, et al. Enzyme-replacement therapy with agalsidase alfa in children with Fabry disease. Pediatrics 2006; 118:924.
  36. Ramaswami U, Wendt S, Pintos-Morell G, et al. Enzyme replacement therapy with agalsidase alfa in children with Fabry disease. Acta Paediatr 2007; 96:122.
  37. Wraith JE, Tylki-Szymanska A, Guffon N, et al. Safety and efficacy of enzyme replacement therapy with agalsidase beta: an international, open-label study in pediatric patients with Fabry disease. J Pediatr 2008; 152:563.
  38. Ramaswami U, Parini R, Pintos-Morell G, et al. Fabry disease in children and response to enzyme replacement therapy: results from the Fabry Outcome Survey. Clin Genet 2012; 81:485.
  39. Schiffmann R, Martin RA, Reimschisel T, et al. Four-year prospective clinical trial of agalsidase alfa in children with Fabry disease. J Pediatr 2010; 156:832.
  40. Pisani A, Spinelli L, Sabbatini M, et al. Enzyme replacement therapy in Fabry disease patients undergoing dialysis: effects on quality of life and organ involvement. Am J Kidney Dis 2005; 46:120.
  41. Pastores GM, Boyd E, Crandall K, et al. Safety and pharmacokinetics of agalsidase alfa in patients with Fabry disease and end-stage renal disease. Nephrol Dial Transplant 2007; 22:1920.
  42. Mignani R, Panichi V, Giudicissi A, et al. Enzyme replacement therapy with agalsidase beta in kidney transplant patients with Fabry disease: a pilot study. Kidney Int 2004; 65:1381.
  43. Mignani R, Feriozzi S, Pisani A, et al. Agalsidase therapy in patients with Fabry disease on renal replacement therapy: a nationwide study in Italy. Nephrol Dial Transplant 2008; 23:1628.
  44. Germain DP, Fan JQ. Pharmacological chaperone therapy by active-site-specific chaperones in Fabry disease: in vitro and preclinical studies. Int J Clin Pharmacol Ther 2009; 47 Suppl 1:S111.
  45. 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.
  46. Tahir H, Jackson LL, Warnock DG. Antiproteinuric therapy and fabry nephropathy: sustained reduction of proteinuria in patients receiving enzyme replacement therapy with agalsidase-beta. J Am Soc Nephrol 2007; 18:2609.
  47. Feriozzi S, Torras J, Cybulla M, et al. The effectiveness of long-term agalsidase alfa therapy in the treatment of Fabry nephropathy. Clin J Am Soc Nephrol 2012; 7:60.
  48. Warnock DG, Thomas CP, Vujkovac B, et al. Antiproteinuric therapy and Fabry nephropathy: factors associated with preserved kidney function during agalsidase-beta therapy. J Med Genet 2015; 52:860.
  49. Batista EC, Carvalho LR, Casarini DE, et al. ACE activity is modulated by the enzyme α-galactosidase A. J Mol Med (Berl) 2011; 89:65.
  50. Wanner C, Breunig F. Fabry nephropathy and the case for adjunctive renal therapy. J Am Soc Nephrol 2007; 18:2426.
  51. Desnick R, Ioannou Y, Eng C. Alpha-galactosidase A deficiency: Fabry disease. In: The Metabolic and Molecular Bases of Inherited Disease, 8th ed, Scriver CR, Beaudet AL, Sly WS, et al (Eds), McGraw Hill, New York 2001. p.3733.
  52. Maizel SE, Simmons RL, Kjellstrand C, Fryd DS. Ten-year experience in renal transplantation for Fabry's disease. Transplant Proc 1981; 13:57.
  53. Ojo A, Meier-Kriesche HU, Friedman G, et al. Excellent outcome of renal transplantation in patients with Fabry's disease. Transplantation 2000; 69:2337.
  54. Shah T, Gill J, Malhotra N, et al. Kidney transplant outcomes in patients with Fabry disease. Transplantation 2009; 87:280.
  55. Alroy J, Sabnis S, Kopp JB. Renal pathology in Fabry disease. J Am Soc Nephrol 2002; 13 Suppl 2:S134.
  56. Gantenbein H, Bruder E, Burger HR, et al. Recurrence of Fabry's disease in a renal allograft 14 years after transplantation. Nephrol Dial Transplant 1995; 10:287.
  57. Peces R. Is there true recurrence of Fabry's disease in the transplanted kidney? Nephrol Dial Transplant 1996; 11:561.
  58. Thadhani R, Wolf M, West ML, et al. Patients with Fabry disease on dialysis in the United States. Kidney Int 2002; 61:249.
  59. Tsakiris D, Simpson HK, Jones EH, et al. Report on management of renale failure in Europe, XXVI, 1995. Rare diseases in renal replacement therapy in the ERA-EDTA Registry. Nephrol Dial Transplant 1996; 11 Suppl 7:4.
  60. Wagner M, Krämer J, Blohm E, et al. Kidney function as an underestimated factor for reduced health related quality of life in patients with Fabry disease. BMC Nephrol 2014; 15:188.
  61. Branton MH, Schiffmann R, Sabnis SG, et al. Natural history of Fabry renal disease: influence of alpha-galactosidase A activity and genetic mutations on clinical course. Medicine (Baltimore) 2002; 81:122.
  62. 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.
  63. Warnock DG, Ortiz A, Mauer M, et al. Renal outcomes of agalsidase beta treatment for Fabry disease: role of proteinuria and timing of treatment initiation. Nephrol Dial Transplant 2012; 27:1042.
  64. Breunig F, Weidemann F, Strotmann J, et al. Clinical benefit of enzyme replacement therapy in Fabry disease. Kidney Int 2006; 69:1216.
  65. Feriozzi S, Schwarting A, Sunder-Plassmann G, et al. Agalsidase alfa slows the decline in renal function in patients with Fabry disease. Am J Nephrol 2009; 29:353.