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Diagnostic accuracy of holotranscobalamin, methylmalonic acid, serum cobalamin, and other indicators of tissue vitamin B₁₂ status in the elderly.
Clin Chem 2011; 57(6):856-63CC

Abstract

BACKGROUND

Vitamin B₁₂ deficiency is common among the elderly, and early detection is clinically important. However, clinical signs and symptoms have limited diagnostic accuracy and there is no accepted reference test method.

METHODS

In elderly subjects (n = 700; age range 63-97 years), we investigated the ability of serum cobalamin, holotranscobalamin (holoTC), total homocysteine (tHcy), methylmalonic acid (MMA), serum and erythrocyte folate, and other hematologic variables to discriminate cobalamin deficiency, defined as red blood cell cobalamin <33 pmol/L.

RESULTS

Serum holoTC was the best predictor, with area under the ROC curve (95% CI) 0.90 (0.86-0.93), and this was significantly better (P ≤ 0.0002) than the next best predictors; serum cobalamin, 0.80 (0.75-0.85), and MMA, 0.78 (0.72-0.83). For these 3 analytes, we constructed a 3-zone partition of positive and negative zones and a deliberate indeterminate zone between. The boundaries were values of each test that resulted in a posttest probability of deficiency of 60% and a posttest probability of no deficiency of 98%. The proportion of indeterminate observations for holoTC, cobalamin, and MMA was 14%, 45%, and 50%, respectively. Within the holoTC indeterminate zone (defined as 20-30 pmol/L), discriminant analysis selected only erythrocyte folate, which correctly allocated 65% (58/89) of the observations. Renal dysfunction compromised the diagnostic accuracy of MMA but not holoTC or serum cobalamin.

CONCLUSIONS

This study supports the use of holoTC as the first-line diagnostic procedure for vitamin B₁₂ status.

Authors+Show Affiliations

Axis-Shield Diagnostics, Dundee, UK. edward_valente@btinternet.comNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

21482749

Citation

Valente, Edward, et al. "Diagnostic Accuracy of Holotranscobalamin, Methylmalonic Acid, Serum Cobalamin, and Other Indicators of Tissue Vitamin B₁₂ Status in the Elderly." Clinical Chemistry, vol. 57, no. 6, 2011, pp. 856-63.
Valente E, Scott JM, Ueland PM, et al. Diagnostic accuracy of holotranscobalamin, methylmalonic acid, serum cobalamin, and other indicators of tissue vitamin B₁₂ status in the elderly. Clin Chem. 2011;57(6):856-63.
Valente, E., Scott, J. M., Ueland, P. M., Cunningham, C., Casey, M., & Molloy, A. M. (2011). Diagnostic accuracy of holotranscobalamin, methylmalonic acid, serum cobalamin, and other indicators of tissue vitamin B₁₂ status in the elderly. Clinical Chemistry, 57(6), pp. 856-63. doi:10.1373/clinchem.2010.158154.
Valente E, et al. Diagnostic Accuracy of Holotranscobalamin, Methylmalonic Acid, Serum Cobalamin, and Other Indicators of Tissue Vitamin B₁₂ Status in the Elderly. Clin Chem. 2011;57(6):856-63. PubMed PMID: 21482749.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Diagnostic accuracy of holotranscobalamin, methylmalonic acid, serum cobalamin, and other indicators of tissue vitamin B₁₂ status in the elderly. AU - Valente,Edward, AU - Scott,John M, AU - Ueland,Per-Magne, AU - Cunningham,Conal, AU - Casey,Miriam, AU - Molloy,Anne M, Y1 - 2011/04/11/ PY - 2011/4/13/entrez PY - 2011/4/13/pubmed PY - 2011/8/4/medline SP - 856 EP - 63 JF - Clinical chemistry JO - Clin. Chem. VL - 57 IS - 6 N2 - BACKGROUND: Vitamin B₁₂ deficiency is common among the elderly, and early detection is clinically important. However, clinical signs and symptoms have limited diagnostic accuracy and there is no accepted reference test method. METHODS: In elderly subjects (n = 700; age range 63-97 years), we investigated the ability of serum cobalamin, holotranscobalamin (holoTC), total homocysteine (tHcy), methylmalonic acid (MMA), serum and erythrocyte folate, and other hematologic variables to discriminate cobalamin deficiency, defined as red blood cell cobalamin <33 pmol/L. RESULTS: Serum holoTC was the best predictor, with area under the ROC curve (95% CI) 0.90 (0.86-0.93), and this was significantly better (P ≤ 0.0002) than the next best predictors; serum cobalamin, 0.80 (0.75-0.85), and MMA, 0.78 (0.72-0.83). For these 3 analytes, we constructed a 3-zone partition of positive and negative zones and a deliberate indeterminate zone between. The boundaries were values of each test that resulted in a posttest probability of deficiency of 60% and a posttest probability of no deficiency of 98%. The proportion of indeterminate observations for holoTC, cobalamin, and MMA was 14%, 45%, and 50%, respectively. Within the holoTC indeterminate zone (defined as 20-30 pmol/L), discriminant analysis selected only erythrocyte folate, which correctly allocated 65% (58/89) of the observations. Renal dysfunction compromised the diagnostic accuracy of MMA but not holoTC or serum cobalamin. CONCLUSIONS: This study supports the use of holoTC as the first-line diagnostic procedure for vitamin B₁₂ status. SN - 1530-8561 UR - https://www.unboundmedicine.com/medline/citation/21482749/Diagnostic_accuracy_of_holotranscobalamin_methylmalonic_acid_serum_cobalamin_and_other_indicators_of_tissue_vitamin_B₁₂_status_in_the_elderly_ L2 - http://www.clinchem.org/cgi/pmidlookup?view=long&amp;pmid=21482749 DB - PRIME DP - Unbound Medicine ER -