Anaemia and Haemoglobinuria Holotranscobalamin – An Early Marker for Laboratory Diagnosis of Vitamin B12 Deficiency

Vitamin B12 deficiency is widespread. Among the population groups at risk are older people, vegetarians, pregnant women and patients with renal or intestinal diseases. The neurological symptoms of vitamin B12 deficiency are unspecific and can be irreversible. Early detection is therefore important. This article reviews the diagnostic performance of the different laboratory markers for vitamin B12 status. Total serum vitamin B12 is a relatively insensitive and unspecific biomarker of deficiency that does not reflect recent variations in cobalamin status. Holotranscobalamin (holoTC), the metabolically active portion of vitamin B12, is the earliest laboratory parameter that becomes decreased in case of a vitamin B12 negative balance. Concentration of methylmalonic acid (MMA) is a functional vitamin B12 marker that will increase when the vitamin B12 stores are depleted. Isolated lowering of holoTC shows vitamin B12 depletion (negative balance), while lowered holoTC plus elevated MMA (and homocysteine) indicates a metabolically manifested vitamin B12 deficiency, although there still may be no clinical symptoms. The diagnostic use of holoTC allows the initiation of therapeutic measures before irreversible neurological damage develops. Because the clinical manifestations of vitamin B12 deficiency are unspecific, people at risk should be identified and should regularly test their holoTC with or without MMA.