Vitamin B12 (Cobalamin)

Overview:

Detect B12 deficiency as in pernicious anemia; diagnose folic acid deficiency; evaluate hypersegmentation of granulocyte nuclei; follow up MCV >100; diagnose macrocytic anemia; diagnose megaloblastic anemia; evaluate alcoholism, prenatal care; evaluate malabsorption, neurological disorders, or the elevation of B12 as seen in liver cell damage or myeloid leukemia.

As with all tests containing monoclonal mouse antibodies, erroneous findings may be obtained from samples taken from patients who have been treated with monoclonal mouse antibodies or have received them for diagnostic purposes.1 In rare cases, interference due to extremely high titers of antibodies to streptavidin and ruthenium can occur.1 The test contains additives, which minimize these effects.

Vitamin B12, or cyanocobalamin, is a complex corrinoid compound containing four pyrrole rings that surround a single cobalt atom.2 Humans obtain vitamin B12 exclusively from animal dietary sources, such as meat, eggs, and milk. Vitamin B12 requires intrinsic factor, a protein secreted by the parietal cells in the gastric mucosa, for absorption. Vitamin B12 and intrinsic factor form a complex that attaches to receptors in the ileal mucosa, where proteins known as transcobalamins transport the vitamin B12 from the mucosal cells to the blood and tissue.3,4 Most vitamin B12 is stored in the liver as well as in the bone marrow and other tissues.

Vitamin B12 and folate are critical to normal DNA synthesis, which in turn affects erythrocyte maturation.3,5,6 Vitamin B12 is also necessary for myelin sheath formation and maintenance.7 The body uses its B12 stores very economically, reabsorbing vitamin B12 from the ileum and returning it to the liver so that very little is excreted.4,8

Clinical and laboratory findings for B12 deficiency include neurological abnormalities, decreased serum B12 levels, and increased excretion of methylmalonic acid.4,8,9 The impaired synthesis associated with vitamin B12 deficiency causes macrocytic anemias. These anemias are characterized by abnormal maturation of erythrocyte precursors in the bone marrow, which results in the presence of megaloblasts and in decreased erythrocyte survival.3,10

Pernicious anemia is a macrocytic anemia caused by vitamin B12 deficiency that is due to lack of intrinsic factor.5,6 Low vitamin B12 intake, gastrectomy, diseases of the small intestine, malabsorption, and transcobalamin deficiency can also cause vitamin B12 deficiency.3

Pregnant women need increased amounts of folate for proper fetal development.11 If a woman has a folate deficiency prior to pregnancy, it will be intensified during gestation and may lead to premature birth and neural tube birth defects, such as spina bifida, in the child.11

1. Vitamin B12 on Elecsys 1010/2010 and Modular Analytics E170, 2007-08, V 4 [package insert]. Indianapolis, Ind: Roche Diagnostics; 2007.

2. Chen IW, Sperling MI, Heminger LA. Vitamin B12. In: Pesce AJ, Kaplan LA, eds.Methods in Clinical Chemistry. St Louis, Mo: CV Mosby;1987: 569-573.

3. Miale JB. Hematology. Laboratory Medicine. St Louis, Mo: CV Mosby;1989: 416-440.

4. Burtis AC, Ashwood ER, eds. "Vitamin B12. Textbook of Clinical Chemistry. Philadelphia, Pa: WB Sanders Co;1996: 2047-2048. 5. Ryan-Harshman M, Aldoori W. Vitamin B12 and health. Can Fam Physician. 2008 Apr; 54(4):536-541. PubMed 18411381

6. Hvas AM, Nexo E. Diagnosis and treatment of vitamin B12 deficiency—An update. Haematologica. 2006 Nov; 91(11):1506-1512. PubMed 17043022

7. Brewster MA. Vitamins. In: Kaplan LA, Pesce AJ, eds. Clinical Chemistry: Theory, Analysis, and Correlation. St. Louis, Mo: CV Mosby;1989:543-568.

8. Steinkamp RC. Vitamin B12 and folic acid: Clinical and pathophysiological considerations. In: Brewster MA, Naito HK, eds. Nutritional Elements and Clinical Biochemistry. New York, NY: Plenum Publishing Corp;1980:169-240.

9. Moretti R, Torre P, Antonello RM, Cattaruzza T, Cazzato G, Bava A. Vitamin B12 and folate depletion in cognition: A review. Neurol India. 2004 Sep; 52(3):310-318. PubMed 15472418

10. Beuerlein FJ. Testing strategies for anemias. Lab Mgmnt. 1988; 23-29.

11. Molloy AM, Kirke PN, Troendle JF, et al. Maternal vitamin B12 status and risk of neural tube defects in a population with high neural tube defect prevalence and no folic acid fortification. Pediatrics. 2009 Marl 123(3):917-923. PubMed 19255021