Vitamin B12 in early childhood: a phenotype-guided approach to deficiency and unexpectedly elevated concentrations

Vitamin B12 deficiency can cause preventable but potentially irreversible neurological injury in infancy, whereas unexpectedly elevated total vitamin B12 creates a different diagnostic challenge. This review outlines a phenotype-guided approach to both findings, emphasizing the mother-infant dyad. Infant deficiency commonly reflects low maternal status, including unrecognized malabsorption despite an omnivorous diet. Neurological manifestations may precede anemia or macrocytosis. Methylmalonic acid and total homocysteine therefore help resolve borderline or clinically discordant vitamin B12 results, although interpretation requires age-specific reference intervals and consideration of renal function. Symptomatic infants generally require prompt parenteral replacement, while selected asymptomatic infants with nutritional deficiency may respond to supervised oral treatment. Newborn screening can identify affected mother-infant dyads but does not exclude deficiency developing later during breastfeeding. Elevated total vitamin B12 most commonly reflects supplementation or altered transport, clearance, or assay characteristics, and should not be equated with toxicity. Persistent unexplained elevation warrants targeted clinical and laboratory assessment.

Integrating clinical phenotype, maternal evaluation, functional biomarkers, and cautious interpretation of elevated concentrations may reduce delayed treatment and unnecessary investigations in infancy and early childhood.

• Infant vitamin B12 deficiency may cause irreversible neurological injury without macrocytic anemia. • Maternal vitamin B12 status strongly influences fetal stores and breastfed-infant risk.

• A phenotype-led framework integrates infant deficiency, maternal assessment, newborn screening, and unexpectedly elevated vitamin B12. • Functional biomarkers help distinguish intracellular deficiency from isolated high total vitamin B12, which is not equivalent to toxicity.