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Purpose Enzyme replacement therapy with alglucosidase alfa for infantile Pompe disease has improved survival creating new management challenges. We describe an emerging phenotype in a retrospective review of long-term survivors. Methods Inclusion criteria included ventilator-free status and age ≤6 months at treatment initiation, and survival to age ≥5 years. Clinical outcome measures included invasive ventilator-free survival and parameters for cardiac, pulmonary, musculoskeletal, gross motor and ambulatory status; growth; speech, hearing, and swallowing; and gastrointestinal and nutritional status. Results Eleven of 17 patients met study criteria. All were cross-reactive immunologic material-positive, alive, and invasive ventilator-free at most recent assessment, with a median age of 8.0 years (range: 5.4 to 12.0 years). All had marked improvements in cardiac parameters. Commonly present were gross motor weakness, motor speech deficits, sensorineural and/or conductive hearing loss, osteopenia, gastroesophageal reflux disease, and dysphagia with aspiration risk. Seven of 11 patients were independently ambulatory and four required the use of assistive ambulatory devices. All long-term survivors had low or undetectable anti-alglucosidase alfa antibody titers. Conclusions Long-term survivors exhibited sustained improvements in cardiac parameters and gross motor function. Residual muscle weakness, hearing loss, risk for arrhythmias, hypernasal speech, dysphagia with risk for aspiration, and osteopenia were commonly observed findings.

Pompe disease is a rare genetic progressive neuromuscular disorder. The most severe form, infantile Pompe disease, has historically resulted in early mortality, most commonly due to cardiorespiratory failure. Treatment with enzyme replacement therapy (ERT) using alglucosidase alfa (Myozyme(®)) has extended the lifespan of individuals with this disease. With the introduction of ERT and the resultant improved survival, dysphagia is being encountered clinically with increasing regularity though systematic data remain unavailable. We retrospectively studied the oropharyngeal swallowing of 13 infants and children with Pompe disease using videofluoroscopy before initiation of ERT, allowing for baseline swallow function to be established in an untreated cohort. Dysphagia was present in all 13 subjects, even in a participant only 15 days old. Oral stage signs were present in 77%, most frequently a weak suck in 69%. Pharyngeal stage signs were present in 100%, including a pharyngeal swallow delay in 92% and pharyngeal residue in 77%. Airway invasion was present in 76.9% of subjects, including penetration in five (38.46%) and silent aspiration in an additional five (38.46%). No relationship in the relative involvement of swallowing, gross motor function, and cardiac disease appeared to be present.

Lingual weakness may be present as an axial sign of LOPD, even relatively early in the disease course, and may contribute to the differential diagnosis of this now treatable condition. Dysphagia and/or dysarthria may also occur. This finding further expands the phenotype of LOPD.

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