Clinical and pathophysiological clues of respiratory dysfunction in late-onset Pompe disease: New insights from a comparative study by MRI and respiratory function assessment
Introduction
Late-onset Pompe disease (LOPD), also known as glycogen storage disease type II (GSDII), is an autosomal recessive inherited disorder, due to a reduced activity of the lysosomal acid alpha-glucosidase (GAA). The deficiency of GAA results in a failure of lysosomal glycogen degradation, leading to a progressive accumulation in several tissues and organs.
LOPD is characterized by progressive limb-girdle weakness and respiratory dysfunction. Since 2006, the enzyme replacement therapy (ERT) represents the only available treatment with a proven efficacy in improving or stabilizing motor and respiratory function in at least 2/3 of LOPD treated patients [1]. However, pulmonary function might progressively deteriorate even in treated patients, likely because ERT was started much after the irreversible muscle damage occurred [2], [3].
Nowadays, respiratory involvement evaluation is based on standard pulmonary function tests which include forced vital capacity (FVC) in sitting and supine position with measurement of the volume drop between the upright and supine positions (FVC drop),that has been suggested as a marker of diaphragmatic dysfunction. Maximal inspiratory/expiratory pressure (MIP/MEP) provides information on respiratory muscle strength rather than capacity as measured by FVC. However, these tests supply limited information about pathophysiological mechanisms of the respiratory failure. Notably, it is still difficult to deeply evaluate the diaphragm function, the most impaired respiratory muscle in LOPD, as well as other muscles devoted to respiration [4].
Several authors focused the attention on a potential role of MRI imaging in the evaluation of diaphragm activity [5], [6], [7], particularly in LOPD [8].
In order to evaluate the ability of MRI in diagnosing the involvement of respiratory muscles in LOPD, we performed MRI evaluation of diaphragm and chest wall muscles activity in 11 patients and five healthy controls, comparing the results with pulmonary function data.
We used a very fast and simple protocol based on the acquisition of one 0.6 second sagittal Balanced Turbo Field Echo (B-TFE) breath hold scan, passing through the center of the right diaphragm both in deep inspiration and expiration. Variation of the lung areas between deep inspiration and expiration and diaphragmatic movement were analyzed and compared with pulmonary function test.
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Patients
The study population included a total of 11 LOPD patients (4 females and 7 males, mean age 44.84, mean weight 72.27 kg, mean height 166.8 cm, Body Mass Index 25.59 and 5 healthy controls (2 females and 3 males, mean age 38.49, mean weight 79.6 kg, mean height 177.2 cm, Body Mass Index 25.38) No significant statistical differences were present between the demographic data of the two groups.
Each patient underwent chest MRI examination as well as pulmonary function tests in the same day after
MR imaging
The imaging data of patients with LOPD and controls are shown in Table 1. In patients, the lung area in maximal inspiration was significantly reduced (P = 0.024) when compared to the control group, while the lung area in maximal expiration did not differ between the two groups. Accordingly, there was a significant maximum difference in lung area delta (P = 0.013) and lung area % (P = 0.007) (Table 1).
On MRI, a marked decreased of C-C distance in maximal inspiration, maximal expiration and delta
Discussion
Respiratory insufficiency is present in the majority of LOPD patients at any age and, even, when they have only mild skeletal muscle symptoms. In 54 patients, Hagemans et al. found that 20 patients utilized ventilatory assistance, having started at a mean age of 49 years, and that 23 patients used a wheelchair, starting at a mean age of 46 years [15]. Fifteen of them used both ventilatory assistance and a wheelchair.
Similarly, Van der Beek et al. found that 59 out of 75 (79%) LOPD patients
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