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

  • Joseph Dian BonduEmail author
  • Arun Jose Nellickal
  • L. Jeyaseelan
  • F. S. Geethanjali
Original Research Article
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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.

Keywords

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

Notes

Acknowledgements

We would like to thank Siemens healthineers for their support.

Compliance with Ethical Standards

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical Approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

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.CrossRefGoogle 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.CrossRefGoogle 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.CrossRefGoogle Scholar
  4. 4.
    Carmel R. Current concepts in cobalamin deficiency. Annu Rev Med. 2000;51:357–75.CrossRefGoogle 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.CrossRefGoogle 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.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.CrossRefGoogle 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.CrossRefGoogle Scholar
  9. 9.
    Carmel R. Measuring and Interpreting Holo-Transcobalamin (Holo-Transcobalamin II). Clin Chem. 2002;48(3):407–9.Google Scholar
  10. 10.
    Hunt A, Harrington D, Robinson S. Vitamin B12 deficiency. BMJ. 2014;349:g5226.CrossRefGoogle 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.CrossRefGoogle 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.CrossRefGoogle 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.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.CrossRefGoogle Scholar
  15. 15.
    Harrington DJ. Laboratory assessment of vitamin B12 status. J Clin Pathol. 2017;70(2):168–73.CrossRefGoogle Scholar
  16. 16.
    Carmel R, Agrawal YP. Failures of cobalamin assays in pernicious anemia. N Engl J Med. 2012;367(4):385–6.CrossRefGoogle 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.CrossRefGoogle 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.CrossRefGoogle 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.CrossRefGoogle Scholar

Copyright information

© Association of Clinical Biochemists of India 2019

Authors and Affiliations

  • Joseph Dian Bondu
    • 1
    Email author
  • Arun Jose Nellickal
    • 1
  • L. Jeyaseelan
    • 2
  • F. S. Geethanjali
    • 1
  1. 1.Department of Clinical BiochemistryChristian Medical CollegeVelloreIndia
  2. 2.Department of BiostatisticsChristian Medical CollegeVelloreIndia

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