Aktuelle Neurologie 2009; 36 - V375
DOI: 10.1055/s-0029-1238490

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

W Schrempf 1, V Neumeister 1, M Eulitz 1, G Siegert 1, H Reichmann 1, S Bergmann 1, A Storch 1
  • 1Dresden

Background: Decreased vitamin B12 (cobalamin) status has been associated with various neurolopsychiatric conditions, such as peripheral neuropathy, subacute combined degeneration, affective disorders and cognitive impairment. Current assays analyze total vitamin B12 concentration, of which only a small percentage is metabolically active. Measurement of its active fraction, holotranscobalamin (holoTC), might be of greater relevance for detecting vitamin B12 deficiency, but data in neuropsychiatric populations are lacking.

Objective: To validate total vitamin B12 and holoTC serum levels for the detection of vitamin B12 deficiency in neuropsychiatric conditions.

Methods: We compared the validity of total serum vitamin B12 with serum holoTC for detection of vitamin B12 deficiency in a patient cohort with neuropsychiatric conditions suspicious for vitamin B12 deficiency. We retrospectively included all patients admitted to our University Department of Neurology between 2005 and 2009 with at least two vitamin B12 serum parameter available (n=1279). We used increased methylmalonic acid (MMA) concentration of >47µg/l as the external validation criteria in the overall cohort (n=749) and in subsets with normal (n=539) and abnormal (n=112) renal function.

Results: Among all patients, 15% had metabolic vitamin B12 deficiency. In receiver operating characteristic curves, correlation of vitamin B12 and holoTC with metabolic vitamin B12 deficiency was generally weak and the areas under the curve (AUC) were not significantly different for holoTC compared with vitamin B12 in all patients (0.59 [95%CI: 0.46–0.72]; p=0.16 vs. 0.68 [0.63–0.74], p<0.0001) and in subsets with normal (AUC: 0.66 [0.51–0.82], p<0.0001 vs. 0.72 [0.65–0.78], p=0.04) and abnormal (AUC: 0.44 [0.21–0.66], p=0.08 vs. 0.61 [0.47–0.74], p=0.62) renal function. The positive predictive values for both holoTC and vitamin B12 were low (20% vs. 32%) and both tests were associated with more false positive than true-positive test results.

Conclusions: HoloTC does not show superior diagnostic accuracy compared with conventional vitamin B12 for the detection of vitamin B12 deficiency in patients with neuropsychiatric conditions. Neither test can be recommended to diagnose vitamin B12 deficiency in patients with neuropsychiatric disorders.