Phrenic Nerve and Diaphragm Electrophysiology in Pompe Disease

Pompe disease is traditionally considered a lysosomal myopathy. However, increasing experimental and clinical evidence suggests involvement of the entire motor unit, including motor neurons, peripheral nerves, neuromuscular junctions, and skeletal muscle. Respiratory impairment is a major cause of morbidity and mortality, and diaphragm dysfunction is frequently observed. Clinical observations at IRCCS Fondazione Mondino have highlighted neurophysiological abnormalities of the phrenic nerve and diaphragm in patients with Pompe disease and respiratory involvement, sometimes occurring even in the absence of clinically significant limb muscle weakness. These findings suggest that respiratory motor unit dysfunction may represent an important component of the disease phenotype. This observational study aims to systematically characterize phrenic nerve conduction parameters and diaphragm electromyographic findings in adult patients with genetically confirmed Pompe disease and in patients with unexplained respiratory failure. Retrospective and prospective clinical, neurophysiological, and respiratory data collected during routine clinical care will be analyzed to explore whether phrenic nerve and diaphragm abnormalities may serve as markers of respiratory motor unit involvement in Pompe disease.

Inclusion Criteria: Age ≥ 18 years. For the prospective cohort: * Genetically confirmed diagnosis of Pompe disease. * Ability to undergo routine neurophysiological and respiratory assessments. * Written informed consent provided. For the retrospective cohort: * History of restrictive respiratory failure or unexplained hypoventilation. * Availability of previous phrenic nerve conduction studies and/or diaphragm electromyography performed as part of routine clinical evaluation. Exclusion Criteria: \- Age \< 18 years. For the prospective cohort: * Conditions preventing completion of neurophysiological assessments (e.g., inability to maintain required positioning or relevant clinical contraindications). * Known primary phrenic nerve injury (e.g., postsurgical phrenic palsy or documented traumatic phrenic neuropathy). * Presence of other neuromuscular disorders potentially confounding data interpretation. * Refusal or inability to provide informed consent. For the retrospective cohort: * Incomplete or technically non-interpretable neurophysiological examinations. * Previously established respiratory or neuromuscular diagnoses fully explaining respiratory impairment. * Cases requiring additional clinical information for study purposes when patient consent for contact or data completion cannot be obtained.