Assessing Diagnostic Accuracy of Serum Holotranscobalamin (Active-B12) in Comparison with Other Markers of Vitamin B12 Deficiency

Abstract

About 15–40% India is Vitamin B12 deficient (commonly diagnosed by total Vitamin B12) but, as only holoTC (active form) is taken up by body cells, thus measuring holoTC is more reflective of Vitamin B12 status than the former. We aimed to assess diagnostic accuracy of serum holoTC in comparison with total Vitamin B12 and total Homocysteine (HCY) as indicator of serum Vitamin B12 status. 217 human subjects (99 males and 118 females) ranging from 17 to 83 years were divided into Vitamin B12 deficient (n = 70), borderline (n = 100) and sufficient groups (n = 47) who were further assessed for markers of Vitamin B12 deficiency—holoTC, HCY, Mean Corpuscular Volume (MCV), Folate, heamoglobin and creatinine. Samples were analysed using Siemens Advia Centaur Xpi. Total Vitamin B12 deficient group had − 84.3% holoTC deficient; 15.7% holoTC sufficient; 72.9% with elevated HCY; 27.1% with normal HCY; 11.4% with megaloblastic anaemia. Borderline group had − 34% holoTC deficient; 28% elevated HCY. A strong positive correlation was found between Total Vitamin B12 and holoTC (r = 0.754, p = <0.001) but strong negative correlation existed between holoTC and HCY (r = − 0.471, p = <0.001). Concordance between Total Vit B12 and HCY (Kappa index = 0.51, p < 0.001); between holoTC and HCY (Kappa index = 0.52, p = <0.001) were statically significant but the latter had a better sensitivity and specificity. Also, statically significant association exists between Total Vitamin B12 and holoTC with HCY (p = <0.001). Therefore, it is ascertained that Active Vitamin B12 assay is a better test and can be considered as an early marker of vitamin B12 deficiency.

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References

  1. 1.

    Devalia V, Hamilton MS, Molloy AM. British committee for standards in haematology. Guidelines for the diagnosis and treatment of cobalamin and folate disorders. Br J Haematol. 2014;166(4):496–513.

    CAS  Article  Google Scholar 

  2. 2.

    Herrmann W, Geisel J. Vegetarian lifestyle and monitoring of vitamin B-12 status. Clin Chim Acta Int J Clin Chem. 2002;326(1–2):47–59.

    CAS  Article  Google Scholar 

  3. 3.

    Clarke R, Refsum H, Birks J, Evans JG, Johnston C, Sherliker P, et al. Screening for vitamin B-12 and folate deficiency in older persons. Am J Clin Nutr. 2003;77(5):1241–7.

    CAS  Article  Google Scholar 

  4. 4.

    Carmel R. Current concepts in cobalamin deficiency. Annu Rev Med. 2000;51:357–75.

    CAS  Article  Google Scholar 

  5. 5.

    Clarke R, Sherliker P, Hin H, Nexo E, Hvas AM, Schneede J, et al. Detection of vitamin B12 deficiency in older people by measuring vitamin B12 or the active fraction of vitamin B12, holotranscobalamin. Clin Chem. 2007;53(5):963–70.

    CAS  Article  Google Scholar 

  6. 6.

    Herrmann W, Obeid R, Schorr H, Geisel J. Functional vitamin B12 deficiency and determination of holotranscobalamin in populations at risk. Clin Chem Lab Med. 2003;41(11):1478–88.

    CAS  PubMed  Google Scholar 

  7. 7.

    Allen RH, Stabler SP, Savage DG, Lindenbaum J. Diagnosis of cobalamin deficiency I: usefulness of serum methylmalonic acid and total homocysteine concentrations. Am J Hematol. 1990;34(2):90–8.

    CAS  Article  Google Scholar 

  8. 8.

    Schmedes A, Brandslund I. Analysis of methylmalonic acid in plasma by liquid chromatography-tandem mass spectrometry. Clin Chem. 2006;52(4):754–7.

    CAS  Article  Google Scholar 

  9. 9.

    Carmel R. Measuring and Interpreting Holo-Transcobalamin (Holo-Transcobalamin II). Clin Chem. 2002;48(3):407–9.

    CAS  Article  Google Scholar 

  10. 10.

    Hunt A, Harrington D, Robinson S. Vitamin B12 deficiency. BMJ. 2014;349:g5226.

    Article  Google Scholar 

  11. 11.

    Nexo E, Hoffmann-Lücke E. Holotranscobalamin, a marker of vitamin B-12 status: analytical aspects and clinical utility. Am J Clin Nutr. 2011;94(1):359S–65S.

    CAS  Article  Google Scholar 

  12. 12.

    Hvas A-M, Nexo E. Holotranscobalamin—a first choice assay for diagnosing early vitamin B deficiency? J Intern Med. 2005;257(3):289–98.

    CAS  Article  Google Scholar 

  13. 13.

    Obeid R, Herrmann W. Holotranscobalamin in laboratory diagnosis of cobalamin deficiency compared to total cobalamin and methylmalonic acid. Clin Chem Lab Med. 2007;45(12):1746–50.

    CAS  PubMed  Google Scholar 

  14. 14.

    Herbert V, Fong W, Gulle V, Stopler T. Low holotranscobalamin II is the earliest serum marker for subnormal vitamin B12 (cobalamin) absorption in patients with AIDS. Am J Hematol. 1990;34(2):132–9.

    CAS  Article  Google Scholar 

  15. 15.

    Harrington DJ. Laboratory assessment of vitamin B12 status. J Clin Pathol. 2017;70(2):168–73.

    Article  Google Scholar 

  16. 16.

    Carmel R, Agrawal YP. Failures of cobalamin assays in pernicious anemia. N Engl J Med. 2012;367(4):385–6.

    CAS  Article  Google Scholar 

  17. 17.

    Brady J, Wilson L, McGregor L, Valente E, Orning L. Active B12: a rapid, automated assay for holotranscobalamin on the Abbott AxSYM analyzer. Clin Chem. 2008;54(3):567–73.

    CAS  Article  Google Scholar 

  18. 18.

    Herrmann W, Schorr H, Obeid R, Geisel J. Vitamin B-12 status, particularly holotranscobalamin II and methylmalonic acid concentrations, and hyperhomocysteinemia in vegetarians. Am J Clin Nutr. 2003;78(1):131–6.

    CAS  Article  Google Scholar 

  19. 19.

    Heil SG, de Jonge R, de Rotte MCFJ, van Wijnen M, Heiner-Fokkema RMR, Kobold ACM, 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.

    CAS  Article  Google Scholar 

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Acknowledgements

We would like to thank Siemens healthineers for their support.

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Correspondence to Joseph Dian Bondu.

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Bondu, J.D., Nellickal, A.J., Jeyaseelan, L. et al. Assessing Diagnostic Accuracy of Serum Holotranscobalamin (Active-B12) in Comparison with Other Markers of Vitamin B12 Deficiency. Ind J Clin Biochem 35, 367–372 (2020). https://doi.org/10.1007/s12291-019-00835-y

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Keywords

  • Vitamin B12 deficiency
  • Holotranscobalamin (holoTC)
  • Homocystine (HCY)
  • Vitamin B12
  • Active vitamin B12