Natural history of the respiratory involvement in Anderson-Fabry disease

J Inherit Metab Dis. 2007 Oct;30(5):790-9. doi: 10.1007/s10545-007-0616-9. Epub 2007 Jul 9.

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.

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 %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.

Publication types

  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Age Factors
  • Airway Obstruction*
  • Case-Control Studies
  • Czech Republic
  • Disease Progression
  • Fabry Disease / enzymology
  • Fabry Disease / genetics
  • Fabry Disease / physiopathology*
  • Female
  • Follow-Up Studies
  • Forced Expiratory Volume
  • Genetic Predisposition to Disease
  • Genotype
  • Humans
  • Male
  • Middle Aged
  • Mutation
  • Phenotype
  • Prognosis
  • Respiration*
  • Severity of Illness Index
  • Sex Factors
  • Spirometry
  • Time Factors
  • Vital Capacity
  • alpha-Galactosidase / genetics
  • alpha-Galactosidase / metabolism

Substances

  • alpha-Galactosidase