CHAPTER 28: The Diagnostic Value of Measuring Holotranscobalamin (Active Vitamin B₁₂) in Human Serum: A Clinical Biochemistry Viewpoint

Vitamin B₁₂ (cobalamin) is essential to mammalian intracellular metabolism. The prevalence of subclinical cobalamin deficiency is higher than previously expected in a general population and, to prevent irreversible neurological damage, an early diagnosis is crucial especially in asymptomatic subjects with serum total vitamin B₁₂ (tB₁₂) concentrations within a common reference interval. Only the transcobalamin–cobalamin complex (holotranscobalamin, holoTC, or active vitamin B₁₂), a minor fraction of circulating tB₁₂, is available for ubiquitous cellular uptake and, therefore, physiologically relevant. Serum tB₁₂ assay, the widely applied standard method, has poor predictive value while, according to several studies, holoTC determination represents an early predictor of changes in cobalamin homeostasis from infancy to old age and, consequently, an early diagnostic tool. In routine assessment of cobalamin status, serum holoTC measurement by commercially available assays allows us to identify asymptomatic subjects at high risk of developing cobalamin deficiency due to physiological conditions and/or lifestyle. This new method of diagnosing subclinical cobalamin deficiency has so far been rarely utilized, particularly by Italian clinicians, even though different studies show the diagnostic role of measuring active B₁₂.