This suggestion is strengthened by whole body MRI imaging data showing apparent pathology in lum-bar extensor and abdominal muscles of Pompe patients (Carlieret al., 2011). That study also revealed that patients with the mos timpaired respiratory function had the most substantial alterationsin the intercostal muscles. Respiratory muscle dysfunction and histopathology is also prominent in Pompe animal models (Mahet al., 2007, 2010). For example, the in vitro contractile force generated by the Gaa−/−mouse diaphragm is substantially bluntedcompared to wildtype control mice, and histological and biochemical evaluation shows profound glycogen accumulation. Thus, theliterature has unequivocally established that diaphragm weaknessis a hallmark feature of Pompe disease, and it is likely that the accessory respiratory muscles are also impaired. In this review, however,we emphasize that ventilatory failure in Pompe disease reflectsa complex interplay between neural and muscular function (seeSection 8).