Investigation of the relationship between serum vitamin B12 levels, holotranscobalamin, homocysteine, methyl malonic acid levels and clinical findings in the diagnosis of vitamin B12 deficiency in children

Vitamin B12 is a coenzyme essential for cellular metabolism and DNA synthesis. Its deficiency can lead to growth retardation, neurological dysfunction, and anemia, particularly in children. Nutritional B12 deficiency is prevalent in developing countries like Turkey. However, the sensitivity and specificity of the most commonly used diagnostic tests are not high, making the diagnosis of B12 deficiency challenging. The objective of this study is to evaluate the correlation between serum vitamin B12 levels and the biomarkers holotranscobalamin, homocysteine, and methylmalonic acid, alongside clinical manifestations in the diagnostic assessment of vitamin B12 deficiency in pediatric patients. A prospective controlled study was conducted involving children with serum vitamin B12 levels below 300 pmol/L who presented to the Pediatric Hematology Clinic at Pamukkale University. The results demonstrated significant differences in serum vitamin B12, holotranscobalamin, and homocysteine levels in children with vitamin B12 deficiency. Clinical presentations such as anemia, neurological symptoms, and growth retardation were common. By establishing the deficiency threshold for holotranscobalamin (Holo-TC) at 35 pmol/L, we identified the optimal cut-off point for serum vitamin B12 to be 276.5 pg/mL, achieving a sensitivity of 76% and a specificity of 77%. We recommend adjusting the clinical threshold for vitamin B12 deficiency to 276.5 pg/mL to improve the detection of patients in the gray zone and those with functional B12 deficiency. This study highlights the significance of assessing holotranscobalamin and homocysteine levels alongside serum vitamin B12 for an accurate diagnosis of B12 deficiency in children.