Enzyme Replacement Therapy & Other Therapeutic Frontiers in Infantile Metabolic Disorders.

Abstract

Inborn errors of metabolism are a heterogeneous group of genetic disorders caused by deficiencies in specific enzymes or proteins, leading to toxic substrate accumulation or deficient product formation. Enzyme replacement therapy (ERT) has emerged as a transformative treatment, particularly for lysosomal storage disorders such as infantile-onset Pompe disease. This review explores the evolution, clinical application, and emerging innovations in ERT, focusing on disorders that present during the neonatal and infantile period. Treatment of patients with Pompe disease illustrates the benefits and limitations of ERT. Early intravenous administration of recombinant acid alpha-glucosidase has dramatically improved survival and cardiac function in affected infants. However, challenges such as immunogenicity, limited central nervous system penetration, and variable skeletal muscle response persist. Novel approaches, such as in utero enzyme replacement therapy, show promise in enhancing outcomes through early intervention and immune tolerance induction. This review also examines ERT in other infantile disorders, outlining efficacy and limitations. Expanding therapeutic frontiers-including gene therapy, gene editing, substrate reduction therapy, and stem cell transplantation-are discussed as complementary or alternative strategies. Despite its success, ERT faces barriers including high cost, limited global access, and the need for ongoing surveillance of long-term outcomes. Addressing these challenges requires investment in research, expanded newborn screening, and equitable access to care. ERT continues to reshape the prognosis of several fatal pediatric metabolic disorders, offering hope for improved quality of life and survival through early and innovative interventions.