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Fabry disease: Baseline medical characteristics of a cohort of 1765 males and females in the Fabry Registry

  • ICIEM 2006
  • Published:
Journal of Inherited Metabolic Disease


The Fabry Registry is a global observational research platform established to define outcome data on the natural and treated course of this rare disorder. Participating physicians submit structured longitudinal data to a centralized, confidential database. This report describes the baseline demographic and clinical characteristics of the first 1765 patients (54% males (16% aged < 20 years) and 46% females (13% < 20 years)) enrolled in the Fabry Registry. The median ages at symptom onset and diagnosis were 9 and 23 years (males) and 13 and 32 years (females), respectively, indicating diagnostic delays in both sexes. Frequent presenting symptoms in males included neurological pain (62%), skin signs (31%), gastroenterological symptoms (19%), renal signs (unspecified) (17%), and ophthalmological signs (11%). First symptoms in females included neurological pain (41%), gastroenterological symptoms (13%), ophthalmological (12%), and skin signs (12%). For those patients reporting renal progression, the median age at occurrence was 38 years for both sexes, but onset of cerebrovascular and cardiovascular events was later in females (median 43 and 47 years, respectively) than in males (38 and 41 years, respectively). This paper demonstrates that in spite of the considerable burden of disease in both sexes that begins to manifest in childhood or adolescence, the recognition of the underlying diagnosis is delayed by 14 years in males and 19 years in females. The Fabry Registry provides data that can increase awareness of common symptoms in all age groups, as well as insight into treated and untreated disease course, leading to improved recognition and earlier treatment, and possibly to improved outcomes for affected individuals.

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central nervous system


enzyme replacement therapy

α-Gal A:

α-galactosidase A




Health Insurance Portability and Accountability Act


Institutional Review Board/Ethics Committee


standard deviation


  • Altarescu G, Moore D, Schiffmann R (2002) Natural history of cardiac involvement in hemizygotes Fabry patients [abstract]. Am J Hum Genet 71: 415.

    Article  Google Scholar 

  • Banikazemi M, Bultas J, Waldek S, et al (2007) Agalsidase-beta therapy for advanced Fabry disease: a randomized trial. Ann Intern Med 146: 77–86.

    PubMed  Google Scholar 

  • Beck M, Whybra C, Wendrich K, et al (2001) Anderson—Fabry disease in children and adolescents. Contrib Nephrol 136: 251–255.

    Article  PubMed  Google Scholar 

  • Branton M, Schiffmann R, Kopp JB (2002) Natural history and treatment of renal involvement in Fabry disease. J Am Soc Nephrol 13: 139–143.

    Google Scholar 

  • Cable WJ, Kolodny EH, Adams RD (1982) Fabry disease: impaired autonomic function. Neurology 32: 498–502.

    PubMed  CAS  Google Scholar 

  • Desnick RJ, Ioannou Y, Eng CM (2001) Alpha-galactosidase A deficiency: Fabry disease. In: Scriver CR, Beaudet al, Sly WS, Valle D, eds; Childs B, Kinzler KW, Vogelstein B, assoc, eds. The Metabolic and Molecular Bases of Inherited Disease, 8th edn. New York: McGraw-Hill, 3733–3774.

    Google Scholar 

  • Desnick RJ, Brady R, Barranger J, et al (2003) Fabry disease, an under-recognized multisystemic disorder: expert recommendations for diagnosis, management, and enzyme replacement therapy. Ann Intern Med 138: 338–346.

    PubMed  Google Scholar 

  • Eng CM, Banikazemi M, Gordon RE, et al (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.

    Article  CAS  Google Scholar 

  • Eng CM, Guffon N, Wilcox WR, et al (2001b) Safety and efficacy of recombinant human alpha-galactosidase A—replacement therapy in Fabry's disease. N Engl J Med 345: 9–16.

    Article  CAS  Google Scholar 

  • Eng CM, Germain DP, Banikazemi M, et al (2006) Fabry disease: guidelines for the evaluation and management of multi-organ system involvement. Genet Med 8: 539–548.

    Article  PubMed  Google Scholar 

  • Gubler MC, Lenoir G, Grunfeld JP, et al (1978) Early renal changes in hemizygous and heterozygous patients with Fabry's disease. Kidney Int 13: 223–235.

    PubMed  CAS  Google Scholar 

  • Lee K, Jin X, Zhang K, et al (2003) A biochemical and pharmacological comparison of enzyme replacement therapies for the glycolipid storage disorder Fabry disease. Glycobiology 13: 305–313.

    Article  PubMed  Google Scholar 

  • MacDermot KD, Holmes A, Miners AH (2001a) Anderson-Fabry disease: clinical manifestations and impact of disease in a cohort of 60 obligate carrier females. J Med Genet 38: 769–775.

    Article  CAS  Google Scholar 

  • MacDermot KD, Holmes A, Miners AH (2001b) Anderson—Fabry disease: clinical manifestations and impact of disease in a cohort of 98 hemizygous males. J Med Genet 38: 750–760.

    Article  CAS  Google Scholar 

  • Mehta A, Ricci R, Widmer U, et al (2004) Fabry disease defined: baseline clinical manifestations of 366 patients in the Fabry Outcome Survey. Eur J Clin Invest 34: 236–242.

    Article  PubMed  CAS  Google Scholar 

  • Morgan SH, Rudge P, Smith SJ, et al (1990) The neurological complications of Anderson—Fabry disease (alpha-galactosidase A deficiency)—investigation of symptomatic and presymptomatic patients. Q J Med 75: 491–507.

    PubMed  CAS  Google Scholar 

  • Ramaswami U, Whybra C, Parini R, et al (2006) Clinical manifestations of Fabry disease in children: data from the Fabry Outcome Survey. Acta Paediatr 95: 86–92.

    Article  PubMed  Google Scholar 

  • Ries M, Ramaswami U, Parini R, et al (2003) The early clinical phenotype of Fabry disease: a study on 35 European children and adolescents. Eur J Pediatr 162: 767–772.

    Article  PubMed  Google Scholar 

  • Schiffmann R (2001) Natural history of Fabry disease in males: preliminary observations. J Inherit Metab Dis 24: 15–17.

    Article  PubMed  Google Scholar 

  • Schiffmann R, Murray GJ, Treco D, et al (2000) Infusion of alpha-galactosidase A reduces tissue globotriaosylceramide storage in patients with Fabry disease. Proc Natl Acad Sci USA 97: 365–370.

    Article  PubMed  CAS  Google Scholar 

  • Schiffmann R, Kopp JB, Austin HA, 3rd, et al (2001) Enzyme replacement therapy in Fabry disease: a randomized controlled trial. JAMA 285: 2743–2749.

    Article  PubMed  CAS  Google Scholar 

  • Shelley ED, Shelley WB, Kurczynski TW (1995) Painful fingers, heat intolerance, and telangiectases of the ear: easily ignored childhood signs of Fabry disease. Pediatr Dermatol 12: 215–219.

    PubMed  CAS  Google Scholar 

  • Sher NA, Letson RD, Desnick RJ (1979) The ocular manifestations in Fabry's disease. Arch Ophthalmol 97: 671–676.

    PubMed  CAS  Google Scholar 

  • Sheth KJ, Werlin SL, Freeman ME, et al (1981) Gastrointestinal structure and function in Fabry's disease. Am J Gastroenterol 76: 246–251.

    PubMed  CAS  Google Scholar 

  • Thadhani R, Wolf M, West ML, et al (2002) Patients with Fabry disease on dialysis in the United States. Kidney Int 61: 249–255.

    Article  PubMed  Google Scholar 

  • Thurberg BL, Rennke H, Colvin RB, et al (2002) Globotriaosylceramide accumulation in the Fabry kidney is cleared from multiple cell types after enzyme replacement therapy. Kidney Int 62: 1933–1946.

    Article  PubMed  CAS  Google Scholar 

  • Thurberg BL, Randolph Byers H, Granter SR, Phelps RG, Gordon RE, O'Callaghan M (2004) Monitoring the 3-year efficacy of enzyme replacement therapy in Fabry disease by repeated skin biopsies. J Invest Dermatol 122: 900–908.

    Article  PubMed  CAS  Google Scholar 

  • Tsakiris D (1996) Rare diseases in renal replacement therapy in the ERA-EDTA registry. Nephrol Dialysis Transpl 11: 4–20.

    Google Scholar 

  • Wilcox WR, Banikazemi M, Guffon N, et al (2004) Long-term safety and efficacy of enzyme replacement therapy for Fabry disease. Am J Hum Genet 75: 65–74.

    Article  PubMed  CAS  Google Scholar 

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Correspondence to C. M. Eng.

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Communicating editor: Verena Peters

Competing interests: Authors may have provided paid and unpaid consultancy services for Genzyme, may have been in receipt of travel expenses to attend meetings and may have participated in a number of clinical trials sponsored by Genzyme. This work was supported by grants from Genzyme Corporation, which also maintains the central Fabry Registry database, but the authors do not have financial interests related to it. All support to physicians participating in the Fabry Registry is conducted under strict guidelines for disclosure and compliance.

References to electronic databases: Fabry disease (OMIM 301500); α-galactosidase A (α-Gal A; EC

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Eng, C.M., Fletcher, J., Wilcox, W.R. et al. Fabry disease: Baseline medical characteristics of a cohort of 1765 males and females in the Fabry Registry. J Inherit Metab Dis 30, 184–192 (2007).

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