A comprehensive study on the effect of alglucosidase alpha and immunomodulation on survival, motor and cardiac outcome, creatine kinase and antibody titers in classic infantile Pompe disease: the Monza experience

We report on 13 classic infantile Pompe patients, including four cross-reactive immunological material negative (31%), treated with alglucosidase alpha (rhGAA) at Fondazione IRCCS San Gerardo, Monza, between 2003 and 2024. Median age at rhGAA initiation was 3.3 months, with nine patients (69%) starting on doses > 20 mg/kg/every other week. With a median follow-up of 6.9 years, the 5- and 10-year survival was 92%. Four patients died, and three became ventilator-dependent. Hypertrophic cardiomyopathy normalized in all patients, though electrocardiogram abnormalities persisted in 36%. Walking was achieved by 10 (77%). Ten patients received immune tolerance induction (77%, five primary, two secondary, three both), and seven received long-term sirolimus. Nine developed anti-rhGAA, of whom five (38%) had high-sustained antibody titers (HSAT). All had elevated creatine kinase at diagnosis; creatine phosphokinase normalized over time in four patients on 40 mg/kg/week since start without HSAT. This study offers real-world insight into managing classic infantile Pompe disease and compares the cohort's outcome to international experiences.