Fig. 1: Model framework.

(a) Clinical identification. ^aCohort of 4,000,000. ^bInfantile-onset Pompe disease was defined as symptom onset prior to 12 months. ^cTwo-thirds of patients identified with infantile-onset Pompe disease without cardiomyopathy experience a delay in treatment and do not start treatment until age 3. ^dMuscle weakness and declining muscle tone, but maintain the ability to walk and perform most activities independently. ^eIncreasing muscle weakness and breathing problems necessitating wheelchair use and ventilator dependence. (b) Newborn screening. ^aInfantile-onset Pompe disease was defined as symptom onset prior to 12 months. ^bMuscle weakness and declining muscle tone, but maintain the ability to walk and perform most activities independently. ^cIncreasing muscle weakness and breathing problems necessitating wheelchair use and ventilator dependence. ^dSince the focus of this study is on screening for and the identification of infantile-onset Pompe, we have not distinguished the potential reasons for false positives such as being heterozygous for a pathogenic variant or other technical reasons. ^eSix of the ten false negatives are expected to have a pseudodeficiency and never develop any symptoms.