Early detection in action: developing and refining newborn screening for Pompe disease in North Carolina

Pompe disease, a lysosomal disease, was added to the Recommended Uniform Screening Panel in 2015, and it has been included in the newborn screening (NBS) panel in North Carolina (NC) since February 2023. Across the world, the approach to NBS for Pompe disease varies. This study adds to the literature 20 months of population level health data from NC regarding infants who screened positive for Pompe disease via NBS. Fifty-two of 228,474 (0.02%) infants screened positive for Pompe disease, and after diagnostic testing, 18 (35%) were diagnosed with presumed late-onset Pompe disease (LOPD), resulting in a higher than previously reported incidence of 1 in 12,693. No infants with the infantile onset form of disease were identified at the time of data closure. While seasonal variations existed in the absolute value of dried blood spot (DBS) acid α-glucosidase (GAA) enzyme activity, this was successfully controlled for using cutoffs defined by the percent of the daily median of enzyme activity. None of the following parameters correlated with the final clinical designation in a statistically significant manner: percent of the daily median DBS GAA enzyme activity, creatine/creatinine/GAA ratio, nor birthweight. The use of the creatine/creatinine/GAA ratio has been eliminated in NC because of these data. The GAA/α-L-iduronidase ratio was statistically significant in its association to final clinical designations of Pompe disease, and thus provides an opportunity to further refine NBS for Pompe disease in NC. The mean GAA enzyme activity was also statistically significantly different based on the age of NBS sample collection. We propose two algorithms that outline 1) an approach to enable timely treatment of the infantile onset form of Pompe disease; and 2) a more detailed approach for reaching a clinical designation after a positive NBS for Pompe disease. Opportunities for growth, remaining questions, and responsible stewardship of our public health resources are discussed.