Clinical profile and utility of biomarkers in children with cobalamin (vitamin B12) deficiency: A cross-sectional study

BackgroundTo assess utility of novel biomarkers in diagnosing children with clinical cobalamin deficiency. Current practice uses total vitamin B12 levels to confirm diagnosis, which lacks sensitivity when used in isolation.MethodsBetween November 2020 and September 2022, a prospective cross-sectional study was carried out in a tertiary teaching hospital. Children between 1 month and 18 years with clinical symptoms/at-risk of developing B12 deficiency were included. Relevant clinical and laboratory information (including total B12 and biomarker levels) was documented. Sensitivity and specificity of individual biomarkers were assessed using 4cB12, an indicator of functional B12 status. Version 4.2.1 of R language was used for statistical analysis.ResultsAnalysis was performed on 67 children. Anorexia, fatigue and behavioural abnormalities were among the leading clinical characteristics. 49% children had peripheral smear (PS) suggestive of cobalamin deficiency, and 43% had low total B12 levels. Among biomarkers, 85% children had low holotranscobalamin (HoloTC), and 73% and 55% had high methylmalonic acid (MMA) and elevated homocysteine (Hcy) levels, respectively. Sensitivity of total B12 was 51%, HoloTC 87%, MMA 83% and Hcy 64%. Combination of low HoloTC, macrocytosis and abnormal PS had 94% sensitivity while HoloTC with mean corpuscular volume (MCV) alone was 88% sensitive in detecting cobalamin deficiency.ConclusionLow total B12 levels lack sensitivity to diagnose cobalamin deficiency. Although combination of low HoloTC with abnormal smear and macrocytosis was found to have better sensitivity, reporting an abnormal smear is time consuming and requires skilled personnel. Combination of low HoloTC with macrocytosis has good sensitivity and can be considered a better screening tool for detecting B12 deficiency.