Infantile-onset Pompe disease entering adulthood: insights from two 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 (IOPD) 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 (CNS) involvement was evaluated using a Modified Fazekas Score (MFS) to grade white matter hyperintensities (WMHI) on brain MRI. RESULTS: Of the initial 11 participants, 8 survived to adulthood (median age 19.6 years); 3 died (2 of arrhythmia, 1 of status epilepticus). All survivors began ERT between 0.2-6 months of age (seven at 20 mg/kg biweekly; one at 40 mg/kg biweekly), with subsequent escalation to 40 mg/kg/week of alglucosidase alfa between ages 8-15 years. None received immune modulation. Cardiac hypertrophy resolved in all; two developed arrhythmias requiring intervention. None required invasive ventilation. Two participants were ambulatory, six used wheelchairs. Flaccid dysarthria (8/8), ptosis (4/8), and sensorineural hearing loss (6/8) were common. WMHI were present in all but remained mild to moderate on MFS. Cognitive function remained stable. CONCLUSIONS: Long-term ERT preserves cardiac and respiratory function in adult IOPD survivors, but multisystem morbidity persists, highlighting the need for earlier diagnosis and better therapies targeting muscle and other tissues including the CNS.

Duke Scholars

Author Priya Sunil Kishnani Pediatrics, Medical Genetics