The objective of this document is to provide health care professionals with recommendations for genetic counseling and testing of individuals with a suspected or confirmed diagnosis of Fabry disease, with a family history of Fabry disease, and those identified as female carriers of Fabry disease. These recommendations are the opinions of a multicenter working group of genetic counselors, medical geneticists, and other health professionals with expertise in Fabry disease counseling, as well as an individual with Fabry disease who is a founder of a Fabry disease patient advocacy group in the United States. The recommendations are U.S. Preventive Task Force Class III, and they are based on clinical experience, a review of pertinent English-language articles, and reports of expert committees. This document reviews the genetics of Fabry disease, the indications for genetic testing and interpretation of results, psychosocial considerations, and references for professional and patient resources. These recommendations should not be construed as dictating an exclusive course of management, nor does use of such recommendations guarantee a particular outcome. The professional judgment of a healthcare provider, familiar with the facts and circumstances of a specific case, will always supersede these recommendations.
This is a preview of subscription content, access via your institution.
Abe A, Gregory S, Lee L, Killen PD, Brady RO, Kulkarni A, Shayman JA (2000) Reduction of globotriaosylceramide in Fabry disease mice by substrate deprivation.J Clin Invest 105:1563–1571.
Abreo K, Oberley TD, Gilbert EF, Opitz JM, Updike SJ (1984) Clinicopathological conference: A 29-year old man with recurrent episodes of fever, abdominal pain, and vomiting. Am J Med Genet 18:249–264.
ASHG/ACMG Reports (1995) Points to consider: Ethical, legal and psychological implications of genetic testing in children and adolescents. Am J Hum Genet57:1233–1241.
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.
Ashton-Prolla P, Tong B, Shabeer J, Eng CM, Desnick RJ (2000) 22 novel mutations in the ®-galactosidase A gene and genotype/phenotype correlations including mild hemizygotes and severely affected heterozygotes. J Invest Med 48:227.
Baker DL, Schuette JL, Uhlmann WR (eds) (1998) A Guide to Genetic Counseling. New York: Wiley-Liss.
Bennett RL (1999) The Practical Guide to the Genetic Family History. New York: Wiley-Liss.
Bennett RL, Steinhaus KA, Uhrich SB, O'sullivan CK, Resta RG, Lochner-Doyle D, Markel DS, Vincent V, Hamanishi J (1995) Recommendations for standardized pedigree nomenclature. Am J Hum Genet 56:745–752.
Brady RO, Schiffmann R (2000) Clinical features of and recent advances in therapy for Fabry disease. JAMA 284:2771–2775.
Brown LK, Miller A, Bhuptani A, Sloane MF, Zimmerman MI, Schilero G, Eng CM, Desnick RJ (1997) Pulmonary involvement in Fabry disease. Am J Respir Crit Care Med 155:1005–1110.
Clarke A (ed) (1998) The Genetic Testing of Children. Oxford: BIOS Scientific.
Clarke A, Flinter F (1996) The genetic testing of children: A clinical perspective. In: Marteau T, Richards M (eds) The Troubled Helix: Social and Psychological Implications of the New Human Genetics. New York: Cambridge University Press, pp 164–176.
Colombi A, Kostyal A, Bracher R, Gloor F, Mazzi R, Tholen H (1967) Angiokeratoma corporis diffusum: Fabry's disease. Helv Med Acta 34:67–83.
Davis DS (1997) Genetic dilemmas and the child's right to an open future. Hastings Center Report 27:7–15.
Desnick RJ (2001) Enzyme replacement and beyond. J Inherit Metab Dis 24:251–256.
Desnick RJ, Ioannou A, Eng CM(2001) α;-Galactosidase A deficiency: Fabry disease. In: Scriver CR, Beaudet AL, Sly WS, Valle D (eds) The Metabolic and Molecular Bases of Inherited Disease, 8th edn. New York: McGraw-Hill, pp 3733–3774.
Dinc A, Simsek I, Pay S, Caglar K, Can C (2000) Fabry's disease mimicking familial Mediterranean fever. Clin Exp Rheumatol 18:787–788.
Eng CM, Ashley GA, Burgert TS, Enriquez AL, D'souza M, Desnick RJ (1997) Fabry disease: Thirty-five mutations in the α-galactosidaseAgene in patients with classic and variant phenotypes. Molec Med 3:174–182.
Eng CM, Banikazemi M, Gordon RE, Goldman M, Phelps R, Kim L, Gass A, Winston J, Dikman S, Fallon JT, Brodie S, Stacy CB, Mehta D, Parsons R, Norton K, O'Callaghan M, Desnick RJ (2001a) A phase 1/2 clinical trial of enzyme replacement in Fabry disease: Pharmacokinetic, substrate clearance, and safety studies. Am J Hum Genet 68:711–722.
Eng CM, Guffon N, Wilcox WR, Germain DP, Lee P, Waldek S, Caplan L, Linthorst GE, Desnick RJ (2001b) Safety and efficacy of recombinant human ®-galactosidase A replacement therapy in Fabry's disease. N Engl J Med 345:9–16.
Gahl WA (2001) New therapies for Fabry's disease. N Engl J Med 345:55–57.
Germain DP, Salard D, Fellmann F, Azibi K, Caillaud C, Bernard MC, Poenaru L (2001) Identification of a novel de novo mutation (G373D) in the alpha-galactosidaseAgene (GLA) in a patient affected with Fabry disease. Hum Mutat 17:353.
Grewal RP (1993) Psychiatric disorders in patients with Fabry's disease. Int J Psychiatry Med 23:307–312.
Hallowell N, Murton F (1998) The value of written summaries of genetic consultations. Patient Educ Couns 35:27–34.
Holmes LB, Harvey EA, Coull BA, Huntington KB, Khoshbin S, Hayes AM, Ryan LM (2001) The teratogenicity of anticonvulsant drugs. N Engl J Med 344:1132–1138.
Kodoma K, Kobayashi H, Abe R, Ohkawara A, Yoshii N, Yotsumoto S, Fukushige T, Nagatsuka Y, Hirabayashi Y, Kanzaki T (2001) A new case of α-N-acetylgalactosaminidase deficiency with angiokeratoma corporis diffusum, with Meniere's syndrome and without mental retardation. Br J Derm 144:363–368.
Kuhn H, Kohler E, Hort W, Frenzel H (1982) Concealed myocardial storage disease (Fabry's disease): Pitfalls in the diagnosis of hypertrophic non-obstructive cardiomyopathy. Circulation 66(Suppl II): II–117.
Levade T, Giordano F, Maret A, Maraguery MC, Bazex J, Salvayre R (1991) Case report: Different phenotypic expression of Fabry disease in female monozygotic twins. J Inherit Metab Dis 14:105–1060.
MacDermot KD, Holmes A, Miners AH (2001a) Anderson Fabry disease: Clinical manifestations and impact of disease in a cohort of 98 hemizygous males. J Med Genet 38:750–760.
MacDermot KD, Holmes A, Miners AH (2001b) Anderson Fabry disease: Clinical manifestations and impact of disease in a cohort of 60 obligate carrier females. J Med Genet 38:769–775.
McConkie-Rosell A, DeVellis BM (2000) Threat to parental role: A possible mechanism of altered self-concept related to carrier knowledge. J Genet Counsel 9:285–302.
Meikle PJ, Hopwood JJ, Clague AE, Carey WF (1999) Prevalence of lysosomal storage disorders. JAMA 281:249–254.
Michie S (1996) Predictive genetic testing in children: Paternalism or empiricisms? In: Marteau T, Richards M (eds) The Troubled Helix: Social and Psychological Implications of the New Human Genetics. New York: Cambridge University Press, pp 177–183.
Morgan SH, d'A Crawford M(1988) Anderson-Fabry disease: A commonly missed diagnosis. Br Med J 297:872–873.
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.
National Society of Genetic Counselors (1995) National Society of Genetic Counselors, Position statement on prenatal and childhood testing for adult-onset disorders. Perspect Genet Couns 17:5.
Online Mendelian Inheritance in Man (2000) OMIM (Online Mendelian Inheritance in Man)™ McKusick-Nathans Institute for Genetic Medicine. Johns Hopkins University (Baltimore, MD) and National Center for Biotechnology Information, National Library of Medicine (Bethesda, MD). Available: http://www.ncbi.nlm.nih.gov}/Omim
Peters FP, Sommer A, Vermeulen A, Cheriex EC, Kho TL (1997) Fabry's disease: A multidisciplinary disorder. Postgrad Med J 73:710–712.
Resta RG (ed) (2000) Psyche and Helix, Psychological Aspects of Genetic Counseling. Essays by Seymour Kessler, PhD. New York: Wiley-Liss.
Rosenberg OM, Ferrans VJ, Fulmer JD, Line BR, Barranger JA, Brady RO, Crystal RG (1980) Chronic airflow obstruction in Fabry's disease. Am J Med 68:898–905.
Schiffmann R, Murray GJ, Treco D, Daniel P, Sellos-Moura M, Myers M, Quirk JM, Zirzow GC, Borowski M, Loveday K, Anderson T, Gillespie F, Oliver KL, Jeffries NO, Doo E, Liang TJ, Kreps C, Gunter K, Frei K, Crutchfield K, Selden RF, Brady RO(2000) Infusion of α-galactosidase A reduces tissue globotriaosylceramide storage in patients with Fabry disease. PNAS 97:365–370.
Schiffmann R, Kopp JB, Austin HA, Sabnis S, Moore DF, Weibel T, Balow JE, Brady RO (2001) Enzyme replacement therapy in Fabry Disease. A randomized controlled trial. JAMA 285:2743–2749.
Sørensen SA, Hasholt L (1983) Attitudes of persons at risk for Fabry's Disease towards predictive tests and genetic counseling. J Biosoc Sci 15:89–94.
Stryker VL, Kreps C (2001) Fabry disease. AJN 101:39–44.
Sybert V (1997) Genetic Skin Disorders. New York: Oxford University Press.
Topaloglu AK, Ashley GA, Tong B, Shabbeer J, Astrin KH, Eng CM, Desnick RJ (1999) Twenty novel mutations in the alpha-galactosidase A gene causing Fabry disease. Mol Med 5:806–811.
U.S. Preventive Services Task Force (1995) Chairman Harold C Soc J. Guide to Clinical Preventive Services, 2nd edn, Appendix A. U.S. Government Printing Office, Stock No. 907001005158.
Weil J (2000) Psychosocial Genetic Counseling. Oxford: Oxford University Press.
Wertz D, Fanos JH, Reilly PR (1994) Genetic testing for children and adolescents: Who decides? JAMA 272:875–881.
Williams JK, Schutte DL, Evers C, Holkup PA (2000) Redefinition: Coping with normal results from predictive gene testing for neurodegenerative disorders. Res Nurs Health 23:260–269.
Wise D, Wallace HF, Jellinek EH (1962) Angiokeratoma corporis diffusum. Q J Med New Series XXXI(122):177–2120.
About this article
Cite this article
Bennett, R.L., Hart, K.A., O'Rourke, E. et al. Fabry Disease in Genetic Counseling Practice: Recommendations of the National Society of Genetic Counselors. Journal of Genetic Counseling 11, 121–146 (2002). https://doi.org/10.1023/A:1014545521753
- enzyme therapy
- Fabry disease
- genetic counseling
- genetic testing
- National Society of Genetic Counselors
- practice guidelines