Aim: Fabry disease is an X-linked genetic disorder due
to deficiency of the lysosomal enzyme a-galactosidase
A, which leads to the accumulation of neutral glycosphingolipids
within the lysosomes of almost all tissues.
Clinical manifestations usually include acroparaesthesia,
renal insufficiency and cardiomyopathy.
Recently, pulmonary manifestations consisting of
progressive obstructive airway disease have been
reported. The aim of this study was to analyse the
cross-sectional prevalence of airflow obstruction in a
Swiss cohort of patients, and in selected cases, to
evaluate the impact of enzyme replacement therapy
(ERT) with agalsidase alfa (ReplagalTM; TKT - 5S).
Methods: Forty-four patients (27 men, 17 women)
were included in the study and received pulmonary
function testing. Fifteen patients underwent spirometry
after ERT.
Results: Twelve patients (nine men) had chronic
obstructive pulmonary disease according to the
Global Obstructive Lung Disease (GOLD) initiative
criteria: forced expiratory volume (FEV1)/forced
vital capacity (FVC) 50.7), but only one was an
active smoker and one a previous smoker. FEV1/
FVC as percentage predicted was weakly correlated
with age (r=0.42, p=0.005, calculated by Pearson
product-moment correlation), demonstrating that
airway obstruction occurs in the late stages of the
disease. Median FEV1 in patients with obstruction
was 67% of predicted (range, 45-90%). Reversibility
of FEV1 after b2-agonist inhalation never exceeded
8% of predicted. Diffusing capacity of the lung for
carbon monoxide (DLCO) was measured in 13
individuals with a median of 88% of predicted
(range, 39-125%). After 15+9 months of ERT,
spirometry measurements were recorded in 15
patients. Decline in FEV1 was -2+5% of predicted.
(p40.05, measured by the Wilcoxon signed-rank
test). Median change in DLCO was -10% of
predicted (-40 to +25%, p40.05). High resolution
computed tomography scans demonstrated a moderate
thickening of the bronchial wall in affected
individuals, without evidence of emphysema.
Conclusion: We conclude that Fabry disease can be
complicated by significant airway obstruction, particularly
in patients in the advanced stages of the disease,
and that in the period studied, ERT had no demonstrable
impact on pulmonary function.