Infantile-onset Pompe disease entering adulthood: Insights from 2 decades of enzyme replacement therapy experience.

PURPOSE: This study details the long-term clinical outcomes in adult participants with CRIM-positive infantile-onset Pompe disease treated with enzyme replacement therapy (ERT), initially reported in 2012 (n = 11).

METHODS

Medical records were reviewed for multisystem involvement and biomarker trends. Central nervous system involvement was evaluated using a Modified Fazekas Score to grade white matter hyperintensities on brain magnetic resonance imaging.

RESULTS

Of the initial 11 participants, 8 had survived to adulthood (median age 19.6 years), and 3 died (2 of arrhythmia, 1 of status epilepticus). All survivors began ERT between 0.2 to 6 months of age (7 at 20 mg/kg biweekly; 1 at 40 mg/kg biweekly), with subsequent escalation to 40 mg/kg/week of alglucosidase alfa between ages 8 to 15 years. None of the participants received immune modulation. Cardiac hypertrophy was resolved in all; 2 developed arrhythmias requiring intervention. None of the participants required invasive ventilation. Two participants were ambulatory; 6 used wheelchairs. Flaccid dysarthria (8/8), ptosis (4/8), and sensorineural hearing loss (6/8) were common. White matter hyperintensities were present in all but remained mild to moderate on Modified Fazekas Score. Cognitive function remained stable.

CONCLUSION

Long-term ERT preserves cardiac and respiratory function in adult infantile-onset Pompe disease survivors; however, multisystem morbidity persists, highlighting the need for earlier diagnosis and better therapies targeting muscle and other tissues including the central nervous system.