In late-onset disease, progression is slower, and the concern with a gap is loss of respiratory and mobility function that may not be regained. Nexviazyme was approved in the United States in 2021 for late-onset Pompe disease in patients one year and older. Adults with advanced late-onset disease who depend on ventilatory support or have limited respiratory reserve have the least room for functional loss. Cipaglucosidase alfa administered with oral miglustat is an approved alternative for some adults with late-onset disease, and switching involves clinical judgment about disease stage, prior response and antibody status. Infants with infantile-onset disease and adults with advanced late-onset disease, particularly those with limited respiratory reserve.