Current Status of Cellular and Gene-Based Therapies for Congenital Metabolic Disorders: A Review

Congenital metabolic disorders often lead to irreversible organ damage beginning during fetal life or shortly after birth. Advances in prenatal diagnostics have enabled earlier identification of these conditions, creating opportunities for prenatal therapeutic intervention. Preclinical studies have demonstrated that prenatal cell therapies can result in donor cell engraftment, enzyme production, and partial correction of metabolic defects in several disease models. The fetal environment may support immune tolerance and enhance treatment effectiveness. Limited clinical experience suggests that these approaches are feasible and may be beneficial in selected conditions, including lysosomal storage diseases and infantile-onset Pompe disease. In utero gene therapy has also shown long-term metabolic correction in animal models. However, important challenges remain, including limited engraftment, immune responses, vector safety, ethical concerns, and regulatory barriers. Prenatal cellular and gene-based therapies are promising but remain experimental. Current evidence is strongest for biological rationale and preclinical proof of concept; clinical benefit has not yet been established for most disorders. Further clinical studies are needed to determine their safety, efficacy, and future role in the treatment of congenital metabolic disorders. This article reviews the current status of prenatal fetal cellular and gene‑based therapeutic approaches for inborn errors of metabolism.