Genetics of Fabry Disease Follow-up

  • Author: Maryam Banikazemi, MD; Chief Editor: Bruce Buehler, MD   more...
 
Updated: Jul 8, 2009
 

Further Outpatient Care

Genetic counseling is necessary for the proband, and a careful pedigree should be obtained to identify all family members potentially affected by Fabry disease.

Because Fabry disease is an X-linked recessive trait, all daughters of affected males are carriers, and no sons of affected males have the gene for Fabry disease. Typically, mothers of probands are obligate carriers, and their siblings should be considered at risk.

Next

Inpatient & Outpatient Medications

See Treatment.

Previous
Next

Transfer

Transfer to a center with specialists familiar with Fabry disease may be indicated.

Previous
Next

Deterrence/Prevention

Prenatal testing can be performed in women who are pregnant and are carriers of the gene to identify fetuses affected with Fabry disease. A karyotype should be obtained first to identify if the fetus is male. Enzyme activity can then be measured, using either chorionic villus sampling (CVS) or amniotic fluid samples.

If the mutation carried in the family is known, DNA can be isolated from CVS or amniotic fluid samples, and genotyping can be performed.

Previous
Next

Complications

As with all chronic illnesses, patients are at risk for anxiety disorders, depression, or both.

Previous
Next

Prognosis

Prognosis for patients with Fabry disease has improved with the more widespread use of advanced medical techniques, such as hemodialysis and renal transplant.

Enzyme replacement therapy (ERT) has demonstrated favorable results in modifying long-term complications of Fabry disease. Early treatment with ERT to prevent irreversible damage to the organs seems reasonable.

Previous
 
Contributor Information and Disclosures
Author

Maryam Banikazemi, MD  Assistant Professor of Clinical Pediatrics, Department of Clinical and Molecular Genetics, Columbia University College of Physicians and Surgeons; Director of Newborn Screening Program, Director of Lysosomal Storage Disorders Program, Department of Pediatrics, Columbia University Medical Center

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

Disclosure: Nothing to disclose.

Coauthor(s)

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 College of Medical Genetics, American Pediatric Society, American Society for Biochemistry and Molecular Biology, American Society for Clinical Investigation, American Society for Microbiology, American Society of Human Genetics, Central Society for Clinical Research, Eastern Society for Pediatric Research, New York Academy of Sciences, Sigma Xi, Society for Experimental Biology and Medicine, and Society for Pediatric Research

Disclosure: Amicus Therapeutics Consulting fee Consulting; Genzyme Consulting fee Consulting

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.

Specialty Editor Board

Robert D Steiner, MD  Credit Unions for Kids Professor of Pediatric Research; Faculty, Pediatrics, Molecular and Medical Genetics, and Program in Molecular and Cellular Biosciences; Vice Chair for Research in Pediatrics, Doernbecher Children's Hospital, Oregon Health and Science University; Director and Consulting Staff, Metabolic Bone Disease Clinic, Shriner's Hospital

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, American Society of Human Genetics, Oregon Medical Association, Society for Inherited Metabolic Disorders, Society for Pediatric Research, Society for the Study of Inborn Errors of Metabolism, and Western Society for Pediatric Research

Disclosure: Amicus Honoraria Consulting; Actelion Honoraria Consulting; Actelion Honoraria Speaking and teaching; Biomarin Honoraria Consulting; Genzyme Honoraria Consulting; Shire Honoraria Consulting

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.

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 and American College of Medical Genetics

Disclosure: Nothing to disclose.

Paul D Petry, DO, FACOP, FAAP  Consulting Staff, Freeman Pediatric Care, Freeman Health System

Paul D Petry, DO, FACOP, FAAP is a member of the following medical societies: American Academy of Osteopathy, American Academy of Pediatrics, American College of Osteopathic Pediatricians, and American Osteopathic Association

Disclosure: Nothing to disclose.

Chief Editor

Bruce Buehler, MD  Professor, Department of Pediatrics and Genetics, Director RSA, University of Nebraska Medical Center

Bruce Buehler, MD is a member of the following medical societies: American Academy for Cerebral Palsy and Developmental Medicine, American Academy of Pediatrics, American Association on Mental Retardation, American College of Medical Genetics, American College of Physician Executives, American Medical Association, and Nebraska Medical Association

Disclosure: Nothing to disclose.

References

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

  2. [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. Feb 18 2003;138(4):338-46. [Medline]. [Full Text].

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

  4. 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. Jul 2000;48(4):227-35. [Medline].

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

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

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

  8. 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. Apr 2002;11(2):121-46. [Medline].

  9. 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. Jul 1986;83(13):4859-63. [Medline]. [Full Text].

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

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

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

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

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

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

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

  17. 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. Mar 2001;68(3):711-22. [Medline]. [Full Text].

  18. 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. Jul 5 2001;345(1):9-16. [Medline].

  19. 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. May 1998;30(3):842-3. [Medline].

  20. 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. Jul 5 2001;345(1):25-32. [Medline].

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

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

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

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

  25. 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. May 1990;75(277):491-507. [Medline].

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

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

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

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

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

  31. 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. Jan 4 2000;97(1):365-70. [Medline]. [Full Text].

  32. 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. Feb 7 1991;324(6):395-9. [Medline].

  33. 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. Jul 2004;75(1):65-74. [Medline]. [Full Text].

 
Previous
Next
 
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 © 1994-2012 by WebMD LLC.
This website also contains material copyrighted by 3rd parties.

DISCLAIMER: The content of this Website is not influenced by sponsors. The site is designed primarily for use by qualified physicians and other medical professionals. The information contained herein should NOT be used as a substitute for the advice of an appropriately qualified and licensed physician or other health care provider. The information provided here is for educational and informational purposes only. In no way should it be considered as offering medical advice. Please check with a physician if you suspect you are ill.