Functional vitamin B12 deficiency in global developmental delay: Metabolic pathways and biomarker-based assessment
DOI:
https://doi.org/10.14748/nb0qg972Keywords:
global development delay, vitamin B12, holotranscobalamin, homocysteine, methylmalonic acid, biomarkersAbstract
Introduction:
Global developmental delay (GDD) is a heterogeneous neurodevelopmental disorder in which the etiology often remains unclear. Increasing evidence suggests that disturbances in one-carbon metabolism, mitochondrial function, and methylation capacity contribute to its pathogenesis. Vitamin B12 is a key cofactor in these pathways, but routine assessment based on total serum cobalamin may fail to detect intracellular metabolic deficiency.
Aim:
The aim of this article is to analyze cobalamin-dependent metabolic mechanisms and evaluate the diagnostic role of functional biomarkers in children with GDD.
Materials and Methods:
A narrative review was conducted according to SANRA recommendations. A structured search in PubMed, Web of Science, and Scopus (2008–2023) identified studies on vitamin B12 metabolism and biochemical markers in pediatric populations with developmental delay. Original clinical studies were prioritized, while experimental data were used for mechanistic interpretation.
Results:
Vitamin B12 deficiency impairs neurodevelopment through disrupted methylation, mitochondrial dysfunction, oxidative stress, and altered myelination. Total serum vitamin B12 does not reliably reflect cellular availability because only the transcobalamin-bound fraction is biologically active. Functional biomarkers—holotranscobalamin, homocysteine, and methylmalonic acid—provide a more sensitive assessment of intracellular status. Clinical studies show that vitamin B12 deficiency is an important and potentially reversible cause of GDD, although delayed diagnosis may result in persistent deficits. Maternal vitamin B12 status and early metabolic programming also influence neurodevelopmental outcomes.
Conclusion:
Functional vitamin B12 deficiency represents a metabolically defined and potentially treatable subgroup within GDD. A biomarker-based diagnostic approach may improve etiological clarification and support mechanism-based classification and early targeted intervention.
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