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Screening for metabolic vitamin B12 deficiency by holotranscobalamin in patients suspected of vitamin B12 deficiency: a multicentre study.
Ann Clin Biochem. 2012 Mar; 49(Pt 2):184-9.AC

Abstract

BACKGROUND

Vitamin B(12) deficiency occurs frequently, especially among the elderly. However, screening for vitamin B(12) deficiency is hampered by poor sensitivity of the existing total vitamin B(12) assay. Methylmalonic acid (MMA) is considered as the most representative indicator of metabolic vitamin B(12) deficiency and is used as such in this study. The aim of this study was to validate the clinical usefulness of holotranscobalamin (holoTC) as an initial screening assay for metabolic vitamin B(12) deficiency in a mixed patient population.

METHODS

Three hundred and sixty blood samples were collected by five Dutch hospitals. Vitamin B(12) and holoTC in serum were measured (AxSYM; Abbott). MMA in serum was measured by tandem mass spectrometry (LC-MS/MS).

RESULTS

Receiver operating curve (ROC) analysis demonstrated a greater area under the curve (AUC) for holoTC than for vitamin B(12) in detecting vitamin B(12) deficiency characterized by three predefined cut-off levels of MMA. A cut-off value of 32 pmol/L of holoTC resulted in the highest sensitivity (83%) with acceptable specificity (60%) in detecting MMA concentrations above 0.45 μmol/L. The combination of vitamin B(12) and holoTC did not improve diagnostic accuracy at this cut-off level.

CONCLUSIONS

HoloTC has a better diagnostic accuracy than vitamin B(12) and can replace the existing vitamin B(12) assay as a primary screening test in patients suspected of vitamin B(12) deficiency. Critical evaluation of cut-off values of holoTC indicated that a cut-off value of 32 pmol/L can be considered in screening for metabolic vitamin B(12) deficiency (defined by MMA > 0.45μmol/L) in a mixed patient population.

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Authors+Show Affiliations

Heil SG
Department of Clinical Chemistry, Erasmus MC University Medical Center Rotterdam, Rotterdam, The Netherlands. s.heil@erasmusmc.nl
de Jonge R
No affiliation info available
de Rotte MC
No affiliation info available
van Wijnen M
No affiliation info available
Heiner-Fokkema RM
No affiliation info available
Kobold AC
No affiliation info available
Pekelharing JM
No affiliation info available
Adriaansen HJ
No affiliation info available
Sanders E
No affiliation info available
Trienekens PH
No affiliation info available
Rammeloo T
No affiliation info available
Lindemans J
No affiliation info available

MeSH

AdultAgedAged, 80 and overChromatography, LiquidFemaleHumansLimit of DetectionMaleMiddle AgedROC CurveTandem Mass SpectrometryVitamin B 12Vitamin B 12 Deficiency

Pub Type(s)

Journal Article
Multicenter Study

Language

eng

PubMed ID

22302152

Citation

Heil, Sandra G., et al. "Screening for Metabolic Vitamin B12 Deficiency By Holotranscobalamin in Patients Suspected of Vitamin B12 Deficiency: a Multicentre Study." Annals of Clinical Biochemistry, vol. 49, no. Pt 2, 2012, pp. 184-9.
Heil SG, de Jonge R, de Rotte MC, et al. Screening for metabolic vitamin B12 deficiency by holotranscobalamin in patients suspected of vitamin B12 deficiency: a multicentre study. Ann Clin Biochem. 2012;49(Pt 2):184-9.
Heil, S. G., de Jonge, R., de Rotte, M. C., van Wijnen, M., Heiner-Fokkema, R. M., Kobold, A. C., Pekelharing, J. M., Adriaansen, H. J., Sanders, E., Trienekens, P. H., Rammeloo, T., & Lindemans, J. (2012). Screening for metabolic vitamin B12 deficiency by holotranscobalamin in patients suspected of vitamin B12 deficiency: a multicentre study. Annals of Clinical Biochemistry, 49(Pt 2), 184-9. https://doi.org/10.1258/acb.2011.011039
Heil SG, et al. Screening for Metabolic Vitamin B12 Deficiency By Holotranscobalamin in Patients Suspected of Vitamin B12 Deficiency: a Multicentre Study. Ann Clin Biochem. 2012;49(Pt 2):184-9. PubMed PMID: 22302152.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Screening for metabolic vitamin B12 deficiency by holotranscobalamin in patients suspected of vitamin B12 deficiency: a multicentre study. AU - Heil,Sandra G, AU - de Jonge,Robert, AU - de Rotte,Maurits C F J, AU - van Wijnen,Merel, AU - Heiner-Fokkema,Rebecca M R, AU - Kobold,Anneke C Muller, AU - Pekelharing,J Maurits M, AU - Adriaansen,Henk J, AU - Sanders,Edward, AU - Trienekens,Paul H, AU - Rammeloo,Ton, AU - Lindemans,Jan, Y1 - 2012/02/02/ PY - 2012/2/4/entrez PY - 2012/2/4/pubmed PY - 2012/6/5/medline SP - 184 EP - 9 JF - Annals of clinical biochemistry JO - Ann Clin Biochem VL - 49 IS - Pt 2 N2 - BACKGROUND: Vitamin B(12) deficiency occurs frequently, especially among the elderly. However, screening for vitamin B(12) deficiency is hampered by poor sensitivity of the existing total vitamin B(12) assay. Methylmalonic acid (MMA) is considered as the most representative indicator of metabolic vitamin B(12) deficiency and is used as such in this study. The aim of this study was to validate the clinical usefulness of holotranscobalamin (holoTC) as an initial screening assay for metabolic vitamin B(12) deficiency in a mixed patient population. METHODS: Three hundred and sixty blood samples were collected by five Dutch hospitals. Vitamin B(12) and holoTC in serum were measured (AxSYM; Abbott). MMA in serum was measured by tandem mass spectrometry (LC-MS/MS). RESULTS: Receiver operating curve (ROC) analysis demonstrated a greater area under the curve (AUC) for holoTC than for vitamin B(12) in detecting vitamin B(12) deficiency characterized by three predefined cut-off levels of MMA. A cut-off value of 32 pmol/L of holoTC resulted in the highest sensitivity (83%) with acceptable specificity (60%) in detecting MMA concentrations above 0.45 μmol/L. The combination of vitamin B(12) and holoTC did not improve diagnostic accuracy at this cut-off level. CONCLUSIONS: HoloTC has a better diagnostic accuracy than vitamin B(12) and can replace the existing vitamin B(12) assay as a primary screening test in patients suspected of vitamin B(12) deficiency. Critical evaluation of cut-off values of holoTC indicated that a cut-off value of 32 pmol/L can be considered in screening for metabolic vitamin B(12) deficiency (defined by MMA > 0.45μmol/L) in a mixed patient population. SN - 1758-1001 UR - https://www.unboundmedicine.com/medline/citation/22302152/Screening_for_metabolic_vitamin_B12_deficiency_by_holotranscobalamin_in_patients_suspected_of_vitamin_B12_deficiency:_a_multicentre_study_ L2 - https://journals.sagepub.com/doi/10.1258/acb.2011.011039?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub=pubmed DB - PRIME DP - Unbound Medicine ER -