Clinical and pathophysiological clues of respiratory dysfunction in late-onset Pompe disease: New insights from a comparative study by MRI and respiratory function assessment

Abstract

Respiratory insufficiency commonly develops in patients with Late Onset Pompe Disease (LOPD). It is conceivable that a timely starting of enzyme replacement therapy could avoid this life-threatening complication. Respiratory function in LOPD is commonly evaluated with standard pulmonary tests which do not extensively provide an accurate definition of the muscular pathophysiology. In eleven patients with LOPD and five healthy subjects, we compared pulmonary function results with MRI data, based on scans of the right lung acquired on maximum expiration and inspiration. We observed that variations in the cranio-caudal lung height and of lung areas in inspiration and expiration (lung delta) as well as the area of diaphragmatic movement strongly correlated with pulmonary function results. Moreover, MRI data confirmed that development of respiratory insufficiency in LOPD is mainly due to the diaphragmatic weakness with sparing of the antero-posterior chest expansion related to the activity of the intercostal muscles. These results suggest that respiratory muscle MRI is a quick, useful and reproducible tool for patient management as well as a reliable outcome measure for future LOPD therapeutic trials.

Keywords: Diaphragm; Pompe disease; Respiratory muscles MRI.