PULMONARY INVOLVEMENT IN FABRY DISEASE

Fabry disease is an X-linked inborn error of metabolism resulting from deficient activity of alpha-galactosidase A. Although several case re ports have suggested an association between Fabry disease and airway o bstruction, this has not been investigated in a large series of patien ts. We studied 25 unselected, consecutive, enzymatically diagnosed men referred to a General Clinical Research Center for evaluation. Thirty -six percent complained of dyspnea, and 24% had cough and/or wheezing. Symptoms were similar in smokers and nonsmokers. Nine (36%) had airwa y obstruction on spirometry; this finding was associated with age grea ter than or equal to 26 yr (p < 0.05) and dyspnea or wheezing (p < 0.0 05), but only weakly with smoking (p = 0.062). Five of eight patients responded to bronchodilators, but all 10 methacholine challenges were negative. Chest radiographs revealed normal lung fields in 24 patients and streaky bibasilar densities in one. No pulmonary uptake occurred on Ga-67 citrate scans (18 patients) and In-111-tagged leukocyte scans (16 patients). Specific alpha-galactosidase A mutations were identifi ed in 17 patients; all three patients with frameshift mutations and bo th subjects with the D264V missense mutation had obstructive impairmen t. We conclude that airway obstruction commonly occurs in patients wit h Fabry disease regardless of smoking history, and it increases with a ge. The presence of obstruction may be associated with certain mutatio ns and most likely results from fixed narrowing of the airways by accu mulated glycosphingolipid.