Damara Ortiz, MD, Director of the Lysosomal Storage Diseases Program at the University of Pittsburgh Medical Center discusses newborn screening for Pompe disease and mucopolysaccharidosis type 1. She presents an in-depth discussion on the history of lysosomal disorders, the mechanism of the diseases, and recommendations for newborn screening in the United States with a focus specifically on screening in Pennsylvania. Additionally, the treatments available for Pompe disease, though not curative, have significant impact on the patients, and delivering those treatments earlier in the child’s life is key for positive outcomes.