A Retrospective, Multinational, Multicenter Study on the Natural History of Infantile-Onset Pompe Disease

Abstract

Objective To characterize the natural progression of infantile-onset Pompe disease. Study design Retrospective chart reviews of 168 patients with documented acid a- glucosidase deficiency and symptom onset by 12 months of age ; Kaplan-Meier analysis of total and ventilator-free survival time; Cox proportional hazards regression modeling of mortality risk factors. Results The median age at symptom onset was 2.0 months ( range 0 to 12 months), 4.7 months at diagnosis (range: prenatal to 4.2 months). 5.9 months at first ventilator support (range 0.1 to 31.1 months) , and 8.7 months at death (range 0.3 to 73.4 months). Survival rates at 12 months of age were 25.7% overall and 16.9% ventilator- free; at 18 months 12.3% and 6.7%. Cardiomegaly (92%), hypotonia (88%), cardiomyopathy (88%) , respiratory distress( 78%), muscle weakness (63%), feeding difficulties (57%), and failure to thrive (53%) appeared after a median age of similar to 4.0 months. Multiple covariate analysis confirmed that early symptom onset increased risk of early death. Conclusion Despite frequent therapeutic interventions, infantile-onset Pompe disease remains lethal.