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Utility of measuring vitamin B12 and its active fraction, holotranscobalamin, in neurological vitamin B12 deficiency syndromes

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Abstract

Vitamin B12 (VitB12, cobalamin) deficiency has been associated with various neuropsychiatric conditions, such as peripheral neuropathy, subacute combined degeneration, affective disorders, and cognitive impairment. Current assays analyze vitamin B12, of which only a small percentage is metabolically active. Measurement of its active fraction, holotranscobalamin, might be of greater relevance, but data in populations with neuropsychiatric populations are lacking. In this study, in order to validate VitB12 and holotranscobalamin (holoTC) serum levels for the detection of VitB12 deficiency in neuropsychiatric conditions, we compared the validity of VitB12 and holoTC in a patient cohort with neuropsychiatric conditions suspicious for VitB12 deficiency. The cohort included all patients admitted to the Department of Neurology at our university between 2005 and 2009 with at least two parameters of the VitB12 metabolism available (n = 1,279). We used elevated methylmalonic acid as the external validation criterion for VitB12 deficiency and restricted our analyses to subjects with normal renal function. Among all normal renal function patients, 13.2% had VitB12 deficiency. In receiver operating characteristic curve (ROC) analysis, correlation of VitB12 and holoTC with vitamin B12 deficiency was generally weak, and the areas under the curve (AUC) were not significantly different for holoTC compared to vitamin B12 in all subjects (AUC: 0.66 [95%CI: 0.51–0.82]; p = 0.04 vs. 0.72 [0.65–0.78], p < 0.0001) and in subcohorts of patients with classical VitB12 deficiency syndromes. The positive predictive values for holoTC and vitamin B12 were low (14.7 vs. 21.0%) and both were associated with more false-positive than true-positive test results. holoTC does not show superior diagnostic accuracy compared to VitB12 for the detection of VitB12 deficiency in subjects with neuropsychiatric conditions. Neither test can be recommended to diagnose VitB12 deficiency in subjects with neuropsychiatric disorders.

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Authors and Affiliations

  1. Department of Neurology, Dresden University of Technology, Fetscherstrasse 74, 01307, Dresden, Germany

    Wiebke Schrempf, Marco Eulitz, Heinz Reichmann & Alexander Storch

  2. Institute of Clinical Chemistry, Dresden University of Technology, 01307, Dresden, Germany

    Volker Neumeister & Gabriele Siegert

  3. Department of Biometrics and Medical Informatics, Dresden University of Technology, 01307, Dresden, Germany

    Rainer Koch

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  1. Wiebke Schrempf
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  2. Marco Eulitz
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Correspondence to Alexander Storch.

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Schrempf, W., Eulitz, M., Neumeister, V. et al. Utility of measuring vitamin B12 and its active fraction, holotranscobalamin, in neurological vitamin B12 deficiency syndromes. J Neurol 258, 393–401 (2011). https://doi.org/10.1007/s00415-010-5764-4

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  • DOI: https://doi.org/10.1007/s00415-010-5764-4

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