Background: Inborn errors of metabolism (IEMs) represent a diverse group of genetic disorders affecting various metabolic pathways, with an estimated collective incidence of 1 in 2,500 live births. These conditions result from defects in enzymes, transporters, or cofactors involved in cellular metabolism, leading to substrate accumulation, product deficiency, or alternative pathway activation.
Objective: To provide a comprehensive review of IEMs across all major metabolic categories, including carbohydrate, amino acid, lipid, purine-pyrimidine, porphyrin, vitamin, mineral, and organellar metabolism disorders, with detailed case-based analysis and clinical correlations.
Methods: A systematic review of current literature was conducted using PubMed, EMBASE, and Cochrane databases from 1990 to 2024. Representative clinical cases were selected based on diagnostic criteria, clinical presentation patterns, and therapeutic outcomes. Cases were analyzed using standardized parameters including demographics, clinical features, laboratory findings, diagnostic methods, and treatment responses.
Results: Twenty-five representative cases spanning nine major metabolic categories were analyzed. Early diagnosis through newborn screening programs improved outcomes in 78% of treatable conditions. Enzyme replacement therapy showed efficacy in lysosomal storage disorders, while dietary interventions remained cornerstone therapy for amino acid and carbohydrate disorders. Mortality rates varied significantly across categories, with highest rates in mitochondrial disorders (45%) and lowest in vitamin cofactor deficiencies (5%).
Conclusions: IEMs require early recognition and prompt intervention for optimal outcomes. Advances in newborn screening, molecular diagnostics, and targeted therapies have significantly improved prognosis. However, challenges remain in rare disorders, late-onset presentations, and conditions lacking specific treatments. Future directions include gene therapy, precision medicine approaches, and expanded screening programs
