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J Intern Med. 2005 Mar;257(3):289-98.

Holotranscobalamin--a first choice assay for diagnosing early vitamin B deficiency?

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Department of Clinical Biochemistry, Aarhus University Hospital, Aarhus C, Denmark.



The performance of holotranscobalamin (holoTC) was compared with the other markers of vitamin B12 deficiency, and the influence of age, renal function, and thyroid status was examined.


We examined 937 individuals not treated with vitamin B12 but in whom vitamin B12 deficiency was suspected because of a plasma methylmalonic acid (MMA) above 0.28 micromol L(-1) within the past 4 years. Besides laboratory tests, a structured interview and a neurological examination were performed amongst 534 individuals. Amongst these, 140 individuals qualified for a randomized trial (MMA 0.40-2.00 micromol L(-1)). They were randomized to injections with vitamin B12 or placebo and re-examined after 3 months.


One university hospital in Aarhus, Denmark.


The ROC curves indicate that holoTC (AUC: 0.90) compared favourable with plasma vitamin B12 (AUC: 0.85) for identifying individuals likely to have vitamin B12 deficiency (MMA > or =0.75 micromol L(-1) and plasma total homocysteine (tHcy) > or =15 micromol L(-1)), and further that holoTC (AUC: 0.91) might replace combined testing with plasma vitamin B12 and the metabolites. No association was observed between the biochemical markers and symptoms and signs possibly related to vitamin B12 deficiency. HoloTC, TC saturation, plasma vitamin B12, MMA, and tHcy were significantly associated with plasma creatinine (all with P <0.001). Only tHcy was significantly associated with thyroid stimulating hormone (P=0.02).


HoloTC shows promise as first-line tests for diagnosing early vitamin B12 deficiency.

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