Natural history of the respiratory involvement in Anderson–Fabry disease

  • S. Magage
  • J.-C. Lubanda
  • Z. Susa
  • J. Bultas
  • D. Karetová
  • R. Dobrovolný
  • M. Hřebíček
  • D. P. Germain
  • A. Linhart
Original Article

Summary

Background:

Anderson–Fabry disease (AFD) is an X-linked disorder caused by deficient activity of enzyme α-galactosidase A, resulting in the accumulation of glycosphingolipids within lysosomes. Pulmonary involvement in AFD has previously been documented, but until now has been studied only in a few series of patients without any longitudinal follow-up. The aim of this study was to compare spirometric changes in AFD patients with a matched control population and to follow the subsequent progression of the disease.

Materials and methods:

Fifty individuals (27 women, 23 men, mean age 40±14 years) with AFD from 14 families underwent a static spirometric examination under standard conditions. A set of indices was compared with that of the control population. Out of this cohort, 39 individuals not receiving enzyme replacement therapy were longitudinally evaluated (median follow-up time 24 months).

Results:

A clinically significant reduction in spirometric parameters, corresponding to mild to severe airway obstruction, was observed in 26% of women and 61% of men. During the serial follow-up, a significant (p<0.05) age-dependent reduction of predicted %FVC and %FEV1 values was observed in male patients, while the influence of age was not seen in female patients. The %FEF25–75 values decreased by similar degrees in men and women and in older and younger patients, indicating that progressive bronchial disease affects the small airways first.

Conclusions:

We have demonstrated a clinically relevant age- and sex-dependent progressive pulmonary involvement in AFD patients. The effects of enzyme replacement therapy on pulmonary involvement remain to be demonstrated.

References

  1. Banikazemi M, Bultas J, Waldek S, et al (2007) Fabry Disease Clinical Trial Study Group. Agalsidase-beta therapy for advanced Fabry disease: a randomized trial. Ann Intern Med 146: 77–86.PubMedGoogle Scholar
  2. Brown LK, Miller A, Bhuptani A, et al (1997) Pulmonary involvement in Fabry disease. Am J Respir Crit Care Med 155: 1004–1010.PubMedGoogle Scholar
  3. Desnick RJ, Ioannou YA, Eng CM (2001) α-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
  4. Desnick RJ, Brady R, Barranger J, et al (2003) Fabry disease, an under-recognised multisystemic disorder: expert recommendations for diagnosis, management, and enzyme replacement therapy. Ann Intern Med 138: 338–346.PubMedGoogle Scholar
  5. Dobrovolny R, Dvorakova L, Ledvinova J, et al (2005) Relationship between X-inactivation and clinical involvement in Fabry heterozygotes. Eleven novel mutations in the α-galactosidase A gene in the Czech and Slovak population. J Mol Med 3: 647–654.CrossRefGoogle Scholar
  6. Elleder M, Bradova V, Smid F, et al (1990) Cardiocyte storage and hypertrophy as a sole manifestation of Fabry’s disease. Report on a case simulating hypertrophic non-obstructive cardiomyopathy. Virchows Arch A Pathol Anat Histopathol 417: 449–455.CrossRefPubMedGoogle Scholar
  7. Eng CM, Guffon N, Wilcox WR, et al (2001) Safety and efficacy of recombinant human alpha-galactosidase A replacement therapy in Fabry’s disease. N Engl J Med 345: 9–16.CrossRefPubMedGoogle Scholar
  8. Kampmann C, Baehner F, Whybra C, et al (2002) Cardiac manifestations of Anderson–Fabry disease in heterozygous females. J Am Coll Cardiol 40: 1668–1674.CrossRefPubMedGoogle Scholar
  9. Kariman K, Singletary WV Jr, Sieker HO (1978) Pulmonary involvement in Fabry’s disease. Am J Med 64: 911–912.CrossRefPubMedGoogle Scholar
  10. Kelly MM, Leigh R, McKenzie R, et al (2000) Induced sputum examination: diagnosis of pulmonary involvement in Fabry’s disease. Thorax 55: 720–721.CrossRefPubMedGoogle Scholar
  11. Linhart A, Palecek T, Bultas J, et al (2000) New insights in cardiac structural changes in patients with Fabry’s disease. Am Heart J 139: 1101–1108.CrossRefPubMedGoogle Scholar
  12. MacDermot KD, Holmes A, Miners AH (2001) Anderson–Fabry disease: clinical manifestations and impact of disease in a cohort of 60 obligate carrier females. J Med Genet 38: 769–775.CrossRefPubMedGoogle Scholar
  13. Magage S, Lubanda JC, Germain DP, Bultas J, Karetova D, Linhart A (2005) Respiratory involvement in patients with Fabry disease. Med Sci 21(11 Supplement): 37–39.Google Scholar
  14. Quanjer PH, Tammeling GJ, Cotes JE, et al (1993) Lung volumes and forced ventilatory flows. Report Working Party Standardization of Lung Function Tests, European Community for Steel and Coal. Official Statement of the European Respiratory Society. Eur Respir J Suppl 16: 5–40.PubMedGoogle Scholar
  15. Rosenberg DM, Ferrans VJ, Fulmer JD, et al (1980) Chronic airflow obstruction in Fabry’s disease. Am J Med 68: 898–905.CrossRefPubMedGoogle Scholar
  16. Schiffmann R, Kopp JB, Austin HA III, et al (2001) Enzyme replacement therapy in Fabry disease: a randomized controlled trial. JAMA 285: 2743–2749.CrossRefPubMedGoogle Scholar
  17. Siafakas NM, Vermeire P, Pride NB, et al (1995) Optimal assessment and management of chronic obstructive pulmonary disease (COPD). The European Respiratory Society Task Force. Eur Respir J 8: 1398–1420.CrossRefPubMedGoogle Scholar
  18. Smith P, Heath D, Rodgers B, et al (1991) Pulmonary vasculature in Fabry’s disease. Histopathology 19: 567–569.CrossRefPubMedGoogle Scholar
  19. Weidemann F, Breunig F, Beer M, et al (2003) Improvement of cardiac function during enzyme replacement therapy in patients with Fabry disease: a prospective strain rate imaging study. Circulation 108: 1299–1301.CrossRefPubMedGoogle Scholar

Copyright information

© SSIEM and Springer 2007

Authors and Affiliations

  • S. Magage
    • 1
  • J.-C. Lubanda
    • 1
  • Z. Susa
    • 1
  • J. Bultas
    • 1
  • D. Karetová
    • 1
  • R. Dobrovolný
    • 2
  • M. Hřebíček
    • 2
  • D. P. Germain
    • 3
  • A. Linhart
    • 1
  1. 1.Second Department of Internal MedicineCharles University in Prague, First Faculty of MedicinePrague 2Czech Republic
  2. 2.Department of Inherited Metabolic DisordersCharles University in Prague, First Faculty of MedicinePragueCzech Republic
  3. 3.Department of GeneticsGeorges Pompidou European HospitalParisFrance

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