Genetics of Fabry Disease Follow-up
- Author: Robert J Desnick, MD, PhD; Chief Editor: Maria Descartes, MD more...
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.
Inpatient & Outpatient Medications
Transfer to a center with specialists familiar with Fabry disease may be indicated.
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.
As with all chronic illnesses, patients are at risk for anxiety disorders, depression, or both.
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.
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].
[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].
[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].
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].
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].
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].
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].
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].
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].
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].
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].
Brady RO, Schiffmann R. Clinical features of and recent advances in therapy for Fabry disease. JAMA. 2000 Dec 6. 284(21):2771-5. [Medline].
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].
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].
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].
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].
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].
Desnick RJ. Enzyme replacement and enhancement therapies for lysosomal diseases. J Inherit Metab Dis. 2004. 27(3):385-410. [Medline].
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.
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].
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].
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].
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].
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].
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].
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].
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].
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].
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].
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].
Schiffmann R. Enzyme replacement in Fabry disease: the essence is in the kidney. Ann Intern Med. 2007 Jan 16. 146(2):142-4. [Medline].
Schiffmann R. Neuropathy and Fabry disease: pathogenesis and enzyme replacement therapy. Acta Neurol Belg. 2006 Jun. 106(2):61-5. [Medline].
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].
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].
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].
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].