Nutritional and Dietary Management of Inborn Errors of Metabolism: A Review

Abstract

Inborn errors of metabolism (IEMs) are a heterogeneous category of inherited genetic illnesses caused by mutations leading to the lack or complete absence of enzymes, transport proteins or critical cofactors involved in metabolic pathways. These defects disturb normal biochemical pathways and cause the accumulation of toxic metabolites and/or the deficiency of essential metabolic products. Metabolic disorders, if left untreated, can result in severe morbidity, irreversible organ damage, neurodevelopmental disability, and premature mortality. Nutritional and dietary therapy is the cornerstone of management in many IEMs especially the disorders of amino acid metabolism, organic acidemias, fatty acid oxidation disorders and carbohydrate metabolism disorders.
Early discovery through increased newborn screening programs and rapid, individualised dietary management afterward have drastically improved survival, neurocognitive outcomes and general quality of life in affected individuals. Dietary management depends on the specific metabolic defect and generally consists of restriction of substrates which cannot be metabolised appropriately, provision of alternative sources of nutrients and energy, supplementation of deficient metabolites or cofactors and prevention of catabolic states by adequate caloric intake and appropriate feeding strategies. Ongoing nutritional surveillance and periodic metabolic assessment by a multidisciplinary team of health care professionals including metabolic physicians, dietitians, nurses, geneticists and laboratory specialists are essential for optimising growth, neurologic development, metabolic stability and long-term health outcomes.
Recent advances in metabolic medicine such as precision nutrition, specialised medical foods, enteral nutritional support, enzyme replacement therapy, and gene-based therapeutic approaches have further improved the efficacy of nutritional management and expanded treatment options for several IEMs. Here we discuss basic concepts, existing tactics, emerging breakthroughs, problems and future views of nutritional and dietary therapy in patients with inborn errors of metabolism.