Medscape is available in 5 Language Editions – Choose your Edition here.


Genetics of Fabry Disease Medication

  • Author: Robert J Desnick, MD, PhD; Chief Editor: Maria Descartes, MD  more...
Updated: Feb 24, 2016

Medication Summary

Neuropathic pain agents and ERT may be indicated.



Class Summary

These agents are used to relieve neuropathic pain. Phenytoin and carbamazepine are 2 medications used to treat acroparesthesias in patients with Fabry disease. Either drug may be used, although some patients benefit from a combination.

Phenytoin (Dilantin)


Used for analgesia for acroparesthesia. May act in the motor cortex, where it may inhibit spread of seizure activity. Activity of the brainstem centers responsible for the tonic phase of grand mal seizures may also be inhibited. Individualize dose. Administer larger dose before bedtime if dose cannot be equally divided.

Carbamazepine (Tegretol)


Indicated for complex partial seizures and trigeminal neuralgia. May block posttetanic potentiation by reducing summation of temporal stimulation. May reduce polysynaptic responses and block posttetanic potentiation. Following therapeutic response, may reduce dose to minimum effective level or discontinue treatment at least once every 3 mo. Doses are typically lower than those used to treat seizures and are administered once daily.

Gabapentin (Neurontin)


FDA-approved PO medication for management of postherpetic neuralgia. Also FDA approved for the treatment of partial seizures in adults and children. Chemical structure similar to the inhibitory neurotransmitter GABA. Appears to work by raising GABA levels by some effect on a GABA transporter protein. Also decreases activity of voltage-gated calcium channels via binding to a secondary protein. Approved for epilepsy in children. Available as tab, cap, and liquid dosage forms.


Enzyme Replacement Therapy

Class Summary

α -Gal A deficiency leads to the accumulation of GSLs with terminal α -galactosyl residues. Clinical manifestations of Fabry disease are reflected in the tissue target sites of lipid storage. The recombinantly produced enzyme α -Gal A is available in Europe and United States.

Agalsidase alfa (Fabrazyme, Replagal)


Recombinant form of the human enzyme α -Gal A, which is deficient in patients with Fabry disease. Data from clinical trials show a decrease in GL-3 levels following enzyme replacement, reversal in lipid tissue storage, stabilized or improved renal and cardiac function, and reduction or relief of neuropathic pain. Following enzyme replacement, the long-term use of neuropathic pain medication has been reduced. Agalsidase beta (Fabrazyme) is manufactured by Genzyme Corporation (Cambridge, Mass) and is based on expression of the human GLA gene in CHO cells. Agalsidase alfa (Replagal) is manufactured by Transkaryotic Therapies, Inc (Cambridge, Mass) and is based on activation of the human GLA gene expression in human (skin) fibroblasts.

Contributor Information and Disclosures

Robert J Desnick, MD, PhD Dean for Genetics and Genomics, Professor and Chairman, Department of Genetics and Genomic Sciences, Mount Sinai School of Medicine

Robert J Desnick, MD, PhD is a member of the following medical societies: American Society for Biochemistry and Molecular Biology, Eastern Society for Pediatric Research, American College of Medical Genetics and Genomics, American Pediatric Society, American Society for Clinical Investigation, American Society for Microbiology, American Society of Human Genetics, Central Society for Clinical and Translational Research, New York Academy of Sciences, Sigma Xi, Society for Experimental Biology and Medicine, Society for Pediatric Research

Disclosure: Received consulting fee from Amicus Therapeutics for consulting; Received consulting fee from Genzyme for consulting; Received grant/research funds from Genzyme for consulting; Received royalty from Genzyme for none; Received scientific advisory board from Genzyme for none; Received consulting fee from Synageva BioPharma for none; Received stock options from Synageva BioPharma for none; Received royalty from Shire HGT for none.


Kenneth H Astrin, PhD Associate Professor of Human Genetics, Department of Human Genetics, Mount Sinai School of Medicine

Kenneth H Astrin, PhD is a member of the following medical societies: American Society of Human Genetics

Disclosure: Nothing to disclose.

Maryam Banikazemi, MD Assistant Professor of Clinical Pediatrics, New York Medical College

Maryam Banikazemi, MD is a member of the following medical societies: American Academy of Pediatrics, American Society of Human Genetics

Disclosure: Nothing to disclose.

Specialty Editor Board

Mary L Windle, PharmD Adjunct Associate Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Nothing to disclose.

Chief Editor

Maria Descartes, MD Professor, Department of Human Genetics and Department of Pediatrics, University of Alabama at Birmingham School of Medicine

Maria Descartes, MD is a member of the following medical societies: American Academy of Pediatrics, American College of Medical Genetics and Genomics, American Medical Association, American Society of Human Genetics, Society for Inherited Metabolic Disorders, International Skeletal Dysplasia Society, Southeastern Regional Genetics Group

Disclosure: Nothing to disclose.

Additional Contributors

Robert D Steiner, MD Chief Medical Officer, Acer Therapeutics; Clinical Professor, University of Wisconsin School of Medicine and Public Health

Robert D Steiner, MD is a member of the following medical societies: American Academy of Pediatrics, American Association for the Advancement of Science, American College of Medical Genetics and Genomics, American Society of Human Genetics, Society for Inherited Metabolic Disorders, Society for Pediatric Research, Society for the Study of Inborn Errors of Metabolism

Disclosure: Serve(d) as a director, officer, partner, employee, advisor, consultant or trustee for: Acer Therapeutics; Retrophin; Raptor Pharma; Veritas Genetics; Censa Pharma<br/>Received income in an amount equal to or greater than $250 from: Acer Therapeutics; Retrophin; Raptor Pharma; Censa Pharma.

David Flannery, MD, FAAP, FACMG Vice Chair of Education, Chief, Section of Medical Genetics, Professor, Department of Pediatrics, Medical College of Georgia

David Flannery, MD, FAAP, FACMG is a member of the following medical societies: American Academy of Pediatrics, American College of Medical Genetics and Genomics

Disclosure: Nothing to disclose.

  1. Watanabe H, Goto S, Miyashita A, et al. Role of the p.E66Q variant of GLA in the progression of chronic kidney disease. Clin Exp Nephrol. 2014 Apr 10. [Medline].

  2. [Guideline] Eng CM, Germain DP, Banikazemi M, et al. Fabry disease: guidelines for the evaluation and management of multi-organ system involvement. Genet Med. 2006 Sep. 8(9):539-48. [Medline].

  3. [Guideline] 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 Feb 18. 138(4):338-46. [Medline]. [Full Text].

  4. Auray-Blais C, Boutin M, Gagnon R, Dupont FO, Lavoie P, Clarke JT. Urinary globotriaosylsphingosine-related biomarkers for fabry disease targeted by metabolomics. Anal Chem. 2012 Mar 20. 84(6):2745-53. [Medline].

  5. West M, Nicholls K, Mehta A, et al. Agalsidase alfa and kidney dysfunction in Fabry disease. J Am Soc Nephrol. 2009 May. 20(5):1132-9. [Medline]. [Full Text].

  6. Wilcox WR, Linthorst GE, Germain DP, Feldt-Rasmussen U, Waldek S, Richards SM, et al. Anti-a-galactosidase A antibody response to agalsidase beta treatment: Data from the Fabry Registry. Mol Genet Metab. 2012 Mar. 105(3):443-9. [Medline].

  7. Trimarchi H, Canzonieri R, Schiel A, et al. Podocyturia is significantly elevated in untreated vs treated Fabry adult patients. J Nephrol. 2016 Feb 3. [Medline].

  8. Ashton-Prolla P, Tong B, Shabbeer J, et al. Fabry disease: twenty-two novel mutations in the alpha-galactosidase A gene and genotype/phenotype correlations in severely and mildly affected hemizygotes and heterozygotes. J Investig Med. 2000 Jul. 48(4):227-35. [Medline].

  9. Banikazemi M, Bultas J, Waldek S, et al. Agalsidase-beta therapy for advanced Fabry disease: a randomized trial. Ann Intern Med. 2007 Jan 16. 146(2):77-86. [Medline]. [Full Text].

  10. Banikazemi M, Desnick RJ. Does enzyme replacement therapy improve symptoms of Fabry disease in patients undergoing dialysis?. Nat Clin Pract Nephrol. 2006 Feb. 2(2):72-3. [Medline].

  11. Banikazemi M, Ullman T, Desnick RJ. Gastrointestinal manifestations of Fabry disease: clinical response to enzyme replacement therapy. Mol Genet Metab. 2005 Aug. 85(4):255-9. [Medline].

  12. Bennett RL, Hart KA, O'Rourke E, et al. Fabry disease in genetic counseling practice: recommendations of the National Society of Genetic Counselors. J Genet Couns. 2002 Apr. 11(2):121-46. [Medline].

  13. Bishop DF, Calhoun DH, Bernstein HS, et al. Human alpha-galactosidase A: nucleotide sequence of a cDNA clone encoding the mature enzyme. Proc Natl Acad Sci U S A. 1986 Jul. 83(13):4859-63. [Medline]. [Full Text].

  14. Brady RO, Schiffmann R. Clinical features of and recent advances in therapy for Fabry disease. JAMA. 2000 Dec 6. 284(21):2771-5. [Medline].

  15. Bühler FR, Thiel G, Dubach UC, Enderlin F, Gloor F, Tholen H. Kidney transplantation in Fabry's disease. Br Med J. 1973 Jul 7. 3(5870):28-9. [Medline].

  16. Chien YH, Lee NC, Chiang SC, Desnick RJ, Hwu WL. Fabry Disease: Incidence of the Common Later-Onset a -Galactosidase A IVS4+919G>A Mutation in Taiwanese Newborns -- Superiority of DNA-Based to Enzyme-Based Newborn Screening for Common Mutations. Mol Med. 2012 Mar 19. [Medline].

  17. Cho ME, Kopp JB. Fabry disease in the era of enzyme replacement therapy: a renal perspective. Pediatr Nephrol. 2004 Jun. 19(6):583-93. [Medline].

  18. Colombi A, Kostyal A, Bracher R, Gloor F, Mazzi R, Tholen H. Angiokeratoma corporis diffusum--Fabry's disease. Helv Med Acta. 1967 Dec. 34(1):67-83. [Medline].

  19. Crutchfield KE, Patronas NJ, Dambrosia JM, et al. Quantitative analysis of cerebral vasculopathy in patients with Fabry disease. Neurology. 1998 Jun. 50(6):1746-9. [Medline].

  20. Desnick RJ. Enzyme replacement and enhancement therapies for lysosomal diseases. J Inherit Metab Dis. 2004. 27(3):385-410. [Medline].

  21. Desnick RJ, Ioannou YA, Eng CM. a-Galactosidase A deficiency: Fabry disease. Scriver CR, Beaudet AL, Sly WS, eds. In: Metabolic and Molecular Bases of Inherited Disease. 8th ed. McGraw-Hill Professional; 2001. 3733-74.

  22. Eng CM, Banikazemi M, Gordon RE, Goldman M, Phelps R, Kim L, 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 Mar. 68(3):711-22. [Medline]. [Full Text].

  23. 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 Jul 5. 345(1):9-16. [Medline].

  24. Erten Y, Ozdemir FN, Demirhan B, et al. A case of Fabry's disease with normal kidney function at 10 years after successful renal transplantation. Transplant Proc. 1998 May. 30(3):842-3. [Medline].

  25. Frustaci A, Chimenti C, Ricci R, et al. Improvement in cardiac function in the cardiac variant of Fabry's disease with galactose-infusion therapy. N Engl J Med. 2001 Jul 5. 345(1):25-32. [Medline].

  26. Goldman ME, Cantor R, Schwartz MF, et al. Echocardiographic abnormalities and disease severity in Fabry's disease. J Am Coll Cardiol. 1986 May. 7(5):1157-61. [Medline].

  27. Hilz MJ, Brys M, Marthol H. Enzyme replacement therapy improves function of C-, Adelta-, and Abeta-nerve fibers in Fabry neuropathy. Neurology. 2004 Apr 13. 62(7):1066-72. [Medline].

  28. Hilz MJ, Stemper B, Kolodny EH, et al. Lower limb cold exposure induces pain and prolonged small fiber dysfunction in Fabry patients. Pain. 2000 Feb. 84(2-3):361-5. [Medline].

  29. Linthorst GE, De Rie MA, Tjiam KH. Misdiagnosis of Fabry disease: importance of biochemical confirmation of clinical or pathological suspicion. Br J Dermatol. 2004 Mar. 150(3):575-7. [Medline].

  30. 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 May. 75(277):491-507. [Medline].

  31. Ojo A, Meier-Kriesche HU, Friedman G, et al. Excellent outcome of renal transplantation in patients with Fabry's disease. Transplantation. 2000 Jun 15. 69(11):2337-9. [Medline].

  32. Ries M, Clarke JT, Whybra C, et al. Enzyme-replacement therapy with agalsidase alfa in children with Fabry disease. Pediatrics. 2006 Sep. 118(3):924-32. [Medline].

  33. Schiffmann R. Enzyme replacement in Fabry disease: the essence is in the kidney. Ann Intern Med. 2007 Jan 16. 146(2):142-4. [Medline].

  34. Schiffmann R. Neuropathy and Fabry disease: pathogenesis and enzyme replacement therapy. Acta Neurol Belg. 2006 Jun. 106(2):61-5. [Medline].

  35. Schiffmann R, Kopp JB, Austin HA, et al. Enzyme replacement therapy in Fabry disease: a randomized controlled trial. JAMA. 2001 Jun 6. 285(21):2743-9. [Medline].

  36. Schiffmann R, Murray GJ, Treco D, Daniel P, Sellos-Moura M, Myers M, et al. Infusion of alpha-galactosidase A reduces tissue globotriaosylceramide storage in patients with Fabry disease. Proc Natl Acad Sci U S A. 2000 Jan 4. 97(1):365-70. [Medline]. [Full Text].

  37. von Scheidt W, Eng CM, Fitzmaurice TF, et al. An atypical variant of Fabry's disease with manifestations confined to the myocardium. N Engl J Med. 1991 Feb 7. 324(6):395-9. [Medline].

  38. Wilcox WR, Banikazemi M, Guffon N, Waldek S, Lee P, Linthorst GE, et al. Long-term safety and efficacy of enzyme replacement therapy for Fabry disease. Am J Hum Genet. 2004 Jul. 75(1):65-74. [Medline]. [Full Text].

Angiokeratoma is the small punctate reddish-to-bluish angiectases on the umbilicus.
Angiokeratomas are commonly observed as dense cluster of lesions on the flank and private areas.
Corneal verticillata, commonly seen in patients with Fabry disease, detectable by slit lamp examination.
All material on this website is protected by copyright, Copyright © 1994-2016 by WebMD LLC. This website also contains material copyrighted by 3rd parties.