Related Experiment Video
Updated: May 22, 2026
In Vitro Enzyme Measurement to Test Pharmacological Chaperone Responsiveness in Fabry and Pompe Disease
Published on: December 20, 2017
The emerging phenotype of long-term survivors with infantile Pompe disease
Sean N Prater1, Suhrad G Banugaria, Stephanie M DeArmey
1Division of Medical Genetics, Department of Pediatrics, Duke University Medical Center, Durham, NC, USA.
Insights
Long-term survivors of infantile Pompe disease on alglucosidase alfa therapy show improved cardiac function but persistent challenges. Emerging phenotypes include motor weakness, hearing loss, and swallowing difficulties, requiring ongoing management.
Area of Science:
- Biochemistry
- Genetics
- Pediatrics
Background:
- Enzyme replacement therapy (ERT) with alglucosidase alfa has transformed outcomes for infantile Pompe disease, improving survival rates.
- Increased survival presents new challenges in managing the long-term health and developmental trajectory of these patients.
Purpose of the Study:
- To describe the emerging clinical phenotype in long-term survivors of infantile Pompe disease treated with alglucosidase alfa.
- To identify common residual health issues and functional deficits in this patient population.
Main Methods:
- Retrospective review of patients with infantile Pompe disease initiated on alglucosidase alfa at age ≤6 months.
- Inclusion criteria included ventilator-free status and survival to at least 5 years.
- Outcome measures assessed cardiac, pulmonary, musculoskeletal, motor, ambulatory, speech, hearing, swallowing, and gastrointestinal status.
Main Results:
- Eleven patients met criteria, all surviving past 5 years, ventilator-free, and with low antibody titers.
- Significant cardiac improvements were noted, but common findings included gross motor weakness, speech deficits, hearing loss, osteopenia, and dysphagia.
- Seven patients were independently ambulatory, while four required assistive devices.
Conclusions:
- Long-term survivors demonstrate sustained cardiac and gross motor function improvements with alglucosidase alfa therapy.
- Residual challenges such as muscle weakness, hearing impairment, swallowing difficulties, and osteopenia necessitate continued monitoring and management.
- The emerging phenotype highlights the need for comprehensive, multidisciplinary care for these individuals.
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: 5.4-12.0 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, 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.
Conclusion:
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.
