title: Natural history of the respiratory involvement in Anderson-Fabry disease.
abstract: BACKGROUND
  Anderson-Fabry disease (AFD) is an X-linked disorder caused by deficient activity of enzyme alpha-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.
  
  
  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 %FEF(25-75) 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.
authors.affiliation: Second Department of Internal Medicine, Charles University in Prague, First Faculty of Medicine, U Nemocnice 2, 128 08, Prague 2, Czech Republic.
authors.forename: S
authors.initials: S
authors.lastname: Magage
authors.forename: J-C
authors.initials: JC
authors.lastname: Lubanda
authors.forename: Z
authors.initials: Z
authors.lastname: Susa
authors.forename: J
authors.initials: J
authors.lastname: Bultas
authors.forename: D
authors.initials: D
authors.lastname: Karetová
authors.forename: R
authors.initials: R
authors.lastname: Dobrovolný
authors.forename: M
authors.initials: M
authors.lastname: Hrebícek
authors.forename: D P
authors.initials: DP
authors.lastname: Germain
authors.forename: A
authors.initials: A
authors.lastname: Linhart
mesh_terms: D000328:Adult; D000367:Age Factors; D000402:Airway Obstruction; D016022:Case-Control Studies; D018153:Czech Republic; D018450:Disease Progression; D000795:Fabry Disease / Q000201:enzymology / Q000235:genetics / Q000503:physiopathology*; D005260:Female; D005500:Follow-Up Studies; D005541:Forced Expiratory Volume; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D010641:Phenotype; D011379:Prognosis; D012119:Respiration; D012720:Severity of Illness Index; D012737:Sex Factors; D013147:Spirometry; D013997:Time Factors; D014797:Vital Capacity; D000519:alpha-Galactosidase / Q000235:genetics / Q000378:metabolism
chemical_list: D000519:alpha-Galactosidase