Altered activation of the diaphragm in late-onset Pompe disease

•Transdiaphragmatic pressure (PDI) was lower in all patients, compared to controls.•CMAP amplitude was lower in patients who used external ventilatory support.•PDI but not CMAP correlated to clinical estimates of respiratory muscle function.•The results point to a reconfiguration of phrenic output to preserve ventilation.

Pompe disease is an inherited neuromuscular disorder that affects respiratory function and leads to dependence on external ventilatory support. We studied the activation of the diaphragm using bilateral phrenic magnetic stimulation and hypothesized that diaphragm compound muscle action potential (CMAP) amplitude and evoked transdiaphragmatic pressure (Twitch PDI) would correlate to disease severity. Eight patients with late onset Pompe disease (LOPD, aged 14–48 years) and four healthy control subjects completed the tests. Maximal Twitch PDI responses were progressively reduced in patients with LOPD compared to control subjects (1.4–17.1 cm H2O, p < 0.001) and correlated to voluntary functional tests (p < 0.05). Additionally, CMAP amplitude (mA) was lower in the patients who used nighttime or fulltime ventilatory support, when compared to controls and patients who used no ventilatory support (p < 0.005). However, the normalized (%peak) Twitch PDI and CMAP responses were similar between patients and controls. This suggests a loss of functional phrenic motor units in patients, with normal recruitment of remaining motor units.