Vitamin-Responsive Disorders: From Molecular Basis to Clinical Presentation and Therapy.

Vitamin-dependent cofactors are essential for numerous metabolic reactions, and defects affecting their uptake, conversion, utilisation, or regeneration constitute a heterogeneous group of inherited metabolic disorders (IMDs). Although dietary vitamin intake is sufficient to sustain coenzyme synthesis in healthy individuals, it is insufficient in vitamin-responsive IMDs, where pharmacological supplementation can restore deficient metabolic fluxes or stabilise impaired enzymes. This review provides an integrated overview of the biochemical pathways that convert vitamins into their active coenzymes and documents all currently known hereditary disorders responsive to vitamin or coenzyme therapy, along with recommended doses. For each vitamin group (B1, B2, B3, B6, B8, B9, and B12) and BH4, we outline absorption, intracellular trafficking, coenzyme formation and turnover, major clinical phenotypes, diagnostic biomarkers, and vitamin therapeutic considerations, including dose ranges, formulation constraints, and safety issues. The expected therapeutic benefit is graded to assist with clinical decision-making. As many conditions are rare and have only recently been described, the evidence is sometimes limited; therefore, systematic reporting of individual responses, including vitamin forms and dosing, remains essential. Early recognition of vitamin-responsive IMDs is critical, as timely treatment can dramatically alter disease trajectories and, in some cases, fully reverse symptoms.