Pulmonary manifestations and the effectiveness of enzyme replacement therapy in Fabry Disease with the p. Arg227Ter (p.R227) mutation

• Published in: Molecular genetics & genomic medicine Vol. 10; no. 5; pp. e1915 - n/a
• Main Authors: Pietilä‐Effati, Päivi, Söderström, Johan, Saarinen, Jukka T., Löyttyniemi, Eliisa, Kantola, Ilkka
• Format: Journal Article
• Language: English
• Published: United States John Wiley & Sons, Inc 01-05-2022; John Wiley and Sons Inc; Wiley
• Subjects: Age; alpha-Galactosidase - genetics; alpha-Galactosidase - therapeutic use; Chronic obstructive pulmonary disease; Electrocardiography; Enzyme Replacement Therapy; Enzymes; Fabry disease; Fabry Disease - drug therapy; Fabry Disease - genetics; Fabry's disease; Female; Females; Globotriaosylceramide; Humans; Laboratories; Lung; Lung diseases; Male; Males; Metabolites; Mutation; nonsmoker; Obstructive lung disease; Organs; Original; Oxygen consumption; Patients; Pulmonary arteries; Pulmonary functions; Respiratory function; Smoking; Smooth muscle; Spirometry; Values; X chromosomes; Finland; Fabry disease; nonsmoker; enzyme replacement therapy
• ISSN: 2324-9269; 2324-9269
• DOI: 10.1002/mgg3.1915

Background
Fabry disease (FD) is caused by a defect in α‐galactosidase A gene (GLA) which leads to a progressive accumulation of neutral shingolipids, mainly globotriaosylceramide and its metabolites in several organs. Pulmonary manifestations of FD mimic chronic obstructive pulmonary disease and are disproportionate to smoking status. The effect of enzyme replacement therapy (ERT) on pulmonary function is inconclusive.
We studied the effect of ERT on pulmonary function in FD with a mutation p. Arg227Ter (p.R227*) which is one of the most common mutations causing classical FD in Finland and worldwide.
Methods
Patients were annually examined by multidisciplinary team. Based on the maximal pulmonary oxygen consumption at the baseline, either cardiopulmonary exercise test or combination of spirometry and 6‐minute walking test were performed annually during 5‐year follow‐up.
Results
Four males and eight females met the criteria for ERT and were included in this study. Three of 12 patients had obstruction by GOLD criterion before ERT, and one had a borderline obstruction. In 5 years, five patients were classified as obstructive, although the real change in FEV1/FVC was unchanged in the whole cohort. Only one patient was an active smoker.
Conclusion
In nonsmokers, pulmonary manifestations in classical FD are mild and might be stabilized by ERT.
Pulmonary manifestations of Fabry disease mimic chronic obstructive pulmonary disease and are disproportionate to smoking status. The effect of enzyme replacement therapy (ERT) on pulmonary function is inconclusive. In non‐smokers, pulmonary manifestations in classical Fabry disease are mild and might be stabilized by ERT.