Nutrition and Energy Metabolism in the Differential Diagnosis of Ten Clinical Profiles in Neurodevelopmen

Abstract

Background: Research on diet, microbiota, and neurodevelopmental disorders has focused primarily on autism, although treatable metabolic disorders, gastrointestinal symptoms, and treatment-related adverse effects may occur across diverse clinical profiles. Objective: To organize the evidence around ten operational clinical profiles within SMART-NB and examine nutrition, inborn errors of metabolism, mitochondrial function, oxidative stress, folates, allergies, changes in food systems, and the effects of psychotropic drugs. Methods: A critical, nonsystematic narrative review drawing on clinical literature, observational studies, trials, and guidelines, distinguishing evidence from hypotheses. Synthesis: Specific metabolic diseases exist for which dietary therapy modifies outcomes; this does not imply that nonspecific changes in macronutrient intake reverse neuropsychiatric diagnoses. Identifying coexisting nutritional, gastrointestinal, pharmacological, and neurological problems may improve well-being and functioning. Associations between microbiota and neurodevelopment, as well as historical changes in food systems, do not establish causality on their own. In March 2026, the FDA approved leucovorin for cerebral folate deficiency associated with a confirmed FOLR1 variant, not for the general treatment of autism. Conclusion: A stepwise differential and functional assessment is proposed, with prespecified indicators and an agenda for prospective validation of SMART-NB