Journal of Rare Disorders: Diagnosis & Therapy

Pulmonary Manifestations and the Effectiveness of Enzyme replacement in Fabry Disease with the p.R227X Mutation

Introduction: Fabry disease is a rare X-linked multiorgan disease caused by a defect in α-galactosidase A gene which leads to a progressive accumulation of globotriaosylceramide (Gb3) and its metabolites in several organs. Pulmonary manifestations of Fabry disease mimic chronic obstructive pulmonary disease and are disproportionate to smoking status. The effect of enzyme replacement therapy on pulmonary function is inconclusive.

Objectives: We studied the effect of enzyme replacement therapy on pulmonary function in Fabry disease with a classical mutation p.R227X in Finland to minimize confounding factors caused by genetic and environmental variation. R227X is one of the most common mutations causing classical Fabry disease worldwide.

Methods: 12 of 14 patients with R227X met the criteria for enzyme replacement therapy and were included in this study. Based on the maximal pulmonary oxygen consumption at the baseline, either cardiopulmonary exercise test or combination of spirometry and six-minute walking test were performed annually during fiveyear follow-up.

Results: Three of 12 patients had obstruction by the Global Initiative for Obstructive Lung Disease (GOLD) criterion before enzyme replacement therapy, and one had borderline obstruction. In five years, five patients were classified obstructive, although the real change in FEV1/FVC was unchanged in the whole cohort. Only one patient was active smoker.

Conclusion: The findings of our study suggest that pulmonary manifestations in classical Fabry disease are mild in a predominantly non-smoking cohort. Enzyme replacement therapy might stabilize natural history of the lung disease in this condition.

Author(s):

Päivi Pietilä-Effati^1*,  Johan Söderström² , Jukka T. Saarinen³, Eliisa Löyttyniemi⁴, Ilkka Kantola⁵

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