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

摘要

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.