Latest Advancements in Treatment Options for Infantile-Onset Pompe Disease: A Comprehensive Narrative Review

Infantile-onset Pompe disease (IOPD) is a rare genetic disorder associated with a deficiency of a lysosomal enzyme, the acid alpha-glucosidase. It is characterized by the accumulation of lysosomal and non-lysosomal-bound glycogen in various organs, such as the heart, skeletal muscle, and brain tissue, resulting in muscle weakness, hypertrophic cardiomyopathy, respiratory insufficiency, and other complications. Without treatment, IOPD has a very high mortality rate, with patients dying within the first year of life. Over the past few decades, significant therapeutic advancements have been made to improve the prognosis and quality of life for IOPD patients. Enzyme replacement therapy (ERT) with recombinant human GAA has been the cornerstone of treatment, demonstrating efficacy in prolonging survival and reducing cardiac hypertrophy. However, ERT has limitations, including the development of immune responses, inconsistent skeletal muscle uptake, and the inability to cross the brain barrier. Recent research has focused on enhancing ERT through adjunctive therapies such as immune modulation, gene therapy, and chaperone-mediated approaches to improve enzyme delivery and function. Additionally, advancements in early diagnosis, including newborn screening, have enabled timely intervention, which is crucial for better outcomes. This review comprehensively examines the current therapeutic strategies for IOPD, their efficacy, challenges, and future directions for managing this disease.