Vitamin B12 deficiency laboratory findings

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]

Overview

Laboratory Findings

Deficiency is defined as serum B12 levels less than 200 pg/mL (95-100% specific). Borderline B12 levels are defined between 200 and 400 pg/mL.

Vitamin B-12 deficiency may be an explanation for macrocytosis[1]

However, the MCV is not completely accurate.[2][3][4]:

B12 levels are helpful, but imperfect:

Folic acid levels may not help.[9]

Diagnosis may be especially difficult in alcoholics.[10]

Serum B12 levels are often low in B12 deficiency, but if other features of B12 deficiency are present with normal B12 then the diagnosis must not be discounted. One possible explanation for normal B12 levels in B12 deficiency is antibody interference in people with high titres of intrinsic factor antibody.[11] Some researchers propose that the current standard norms of vitamin B12 levels are too low. In Japan, the lowest acceptable level for vitamin B12 in blood has been raised from about 200 picograms/liter (pg/l) = 145 picomol/liter (pm/l) to 550 pg/l = 400 pm/l. [12]

Serum homocysteine and methylmalonic acid levels are considered more reliable indicators of B12 deficiency than the concentration of B12 in blood, see for example research at the St. Louis University.[13] The levels of these substances are high in B12 deficiency and can be helpful if the diagnosis is unclear. Approximately 10% of patients with vitamin B12 levels between 200-400pg/l will have a vitamin B12 deficiency on the basis of elevated levels of homocysteine and methylmalonic acid.

Routine monitoring of methylmalonic acid levels in urine is an option for people who may not be getting enough dietary B12, as a rise in methylmalonic acid levels may be an early indication of deficiency.[14]

If nervous system damage is suspected, B12 analysis in cerebrospinal fluid can also be helpful, though such an invasive test would be applicable only after unrevealing blood testing.[15]

Specific Findings

  • Methylmalonic acid: elevated in B12 deficiency (98% sensitive)
  • Homocysteine: elevated in B12 and folate deficiency.[16]
  • Anti-IF Antibodies (AB): highly specific for PA, but sensitivity only 50-84%
  • Anti-parietal cell ABs: less sensitive and much less specific.

References

  1. Wymer A, Becker DM (1990). "Recognition and evaluation of red blood cell macrocytosis in the primary care setting.". J Gen Intern Med. 5 (3): 192–7. PMID 2341917. 
  2. Oosterhuis WP, Niessen RW, Bossuyt PM, Sanders GT, Sturk A (2000). "Diagnostic value of the mean corpuscular volume in the detection of vitamin B12 deficiency.". Scand J Clin Lab Invest. 60 (1): 9–18. PMID 10757449. 
  3. 3.0 3.1 3.2 Seward SJ, Safran C, Marton KI, Robinson SH (1990). "Does the mean corpuscular volume help physicians evaluate hospitalized patients with anemia?". J Gen Intern Med. 5 (3): 187–91. PMID 2187961. doi:10.1007/BF02600530. 
  4. 4.0 4.1 Savage DG, Lindenbaum J, Stabler SP, Allen RH (1994). "Sensitivity of serum methylmalonic acid and total homocysteine determinations for diagnosing cobalamin and folate deficiencies.". Am J Med. 96 (3): 239–46. PMID 8154512. 
  5. Pruthi RK, Tefferi A (1994). "Pernicious anemia revisited.". Mayo Clin Proc. 69 (2): 144–50. PMID 8309266. 
  6. Lindenbaum J, Savage DG, Stabler SP, Allen RH (1990). "Diagnosis of cobalamin deficiency: II. Relative sensitivities of serum cobalamin, methylmalonic acid, and total homocysteine concentrations.". Am J Hematol. 34 (2): 99–107. PMID 2339684. 
  7. Naurath HJ, Joosten E, Riezler R, Stabler SP, Allen RH, Lindenbaum J (1995). "Effects of vitamin B12, folate, and vitamin B6 supplements in elderly people with normal serum vitamin concentrations.". Lancet. 346 (8967): 85–9. PMID 7603218. 
  8. Matchar DB, McCrory DC, Millington DS, Feussner JR (1994). "Performance of the serum cobalamin assay for diagnosis of cobalamin deficiency.". Am J Med Sci. 308 (5): 276–83. PMID 7977446. 
  9. Ashraf MJ, Cook JR, Rothberg MB (2008). "Clinical utility of folic acid testing for patients with anemia or dementia.". J Gen Intern Med. 23 (6): 824–6. PMC 2517884Freely accessible. PMID 18414954. doi:10.1007/s11606-008-0615-z. 
  10. Savage D, Lindenbaum J (1986). "Anemia in alcoholics.". Medicine (Baltimore). 65 (5): 322–38. PMID 3747828. 
  11. Hamilton MS, Blackmore S, Lee A. (2006). "Possible cause of flase normal B-12 assays (letter)". Brit Med J. 333 (7569): 654–5. 
  12. Mitsuyama Y, Kogoh H. (1988). "Serum and cerebrospinal fluid vitamin B12 levels in demented patients with CH3-B12 treatment.". Japanese Journal of Psychiatry and Neurology. 42 (1): 65–71. 
  13. "Test used to diagnose B12 deficiency may be inadequate". Retrieved 2007-12-04. 
  14. Donaldson MS. Metabolic vitamin B12 status on a mostly raw vegan diet with follow-up using tablets, nutritional yeast, or probiotic supplements. Ann Nutr Metab. 2000;44(5-6):229-34. PMID 11146329.
  15. Devalia V (2006). "Diagnosing vitamin B-12 deficiency on the basis of serum B-12 assay". Brit J Med. 333 (7564): 385–6. PMID 16916826. 
  16. Ankar A, Bhimji SS. PMID 28722952. 



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