Practical Recommendations for Diagnosis and Management of Respiratory Muscle Weakness in Late-Onset Pompe Disease

Abstract

Pompe disease is an autosomal-recessive lysosomal storage disorder characterized by progressive myopathy with proximal muscle weakness, respiratory muscle dysfunction, and cardiomyopathy (in infants only). In patients with juvenile or adult disease onset, respiratory muscle weakness may decline more rapidly than overall neurological disability. Sleep-disordered breathing, daytime hypercapnia, and the need for nocturnal ventilation eventually evolve in most patients. Additionally, respiratory muscle weakness leads to decreased cough and impaired airway clearance, increasing the risk of acute respiratory illness. Progressive respiratory muscle weakness is a major cause of morbidity and mortality in late-onset Pompe disease even if enzyme replacement therapy has been established. Practical knowledge of how to detect, monitor and manage respiratory muscle involvement is crucial for optimal patient care. A multidisciplinary approach combining the expertise of neurologists, pulmonologists, and intensive care specialists is needed. Based on the authors' own experience in over 200 patients, this article conveys expert recommendations for the diagnosis and management of respiratory muscle weakness and its sequelae in late-onset Pompe disease.

Keywords: Pompe disease; cough assistance; mechanical ventilation; neuromuscular disorders; respiratory muscle weakness.

Figure 1

Recommendations for sleep studies in patients with LOPD. Isolated nocturnal tachypnea or lone increase of base excess on early-morning blood gas analysis may both be indicative of nocturnal hypoventilation but do not justify ventilatory support. However, both scenarios should give rise to monitor patients in shorter intervals. ^a sleep disruption, morning headache, daytime hypersomnolence; ^b dyspnea, orthopnea; ^c VC < 50% predicted, VC postural drop > 40%, MIP < 60 cm H₂O, SNIP < 40 cm H₂O. VC, vital capacity; RMW, respiratory muscle weakness; paCO₂, carbon dioxide tension; paO₂, oxygen tension; AHI, apnea hypopnea index; SpO₂, oxygen saturation; tcCO₂, transcutaneous carbon dioxide tension; CPAP, continuous positive airway pressure; OSA, obstructive sleep apnea; PSG, polysomnography; SNIP, sniff nasal inspiratory pressure; MIP maximum inspiratory pressure.