This essential vitamin is a cause of disease when deficient in the body. Etiology of deficiency used to be partly determined using the radioactive Schilling test. As of 2001, the Schilling test is no longer available because of a cut-off of the manufacturer's supply of the radio-labeled in vivo test reagent. The unequivocal diagnosis of pernicious anemia (PA) must now be through a combination of megaloblastic bone marrow plus serum low B12 and one or both of the serum auto-antibodies.

Clinical Signs of Possible Vitamin B12 Deficiency Disease

• acrocytic anemia (megaloblastic bone marrow morphology; but, caution...mixed B12 & iron deficiency can be normocytic [MCV is not elevated]) with elevated MCV.
• clinically-suspect neurological findings

Causes of elevated serum vitamin B12 levels:

• excessive vitamin A or C or multivitamin intake that makes A or C excessive²
• myeloproliferative diseases (pre-leukemia, leukemia, polycythemia vera, & essential thrombocytopenia)²
• benign instances of leukocytosis²
• some carcinoma cases (especially with hepatic metastases)²
• acute or chronic liver disease²
• chronic ingestion of estrogen (birth control pills³ or hormone replacement ?) or anticonvulsants²
• uremia²

Causes of decreased serum levels of vitamin B12:

• if normal range is 200-900 ng/L
  • vit B12 deficient megaloblastic anemia is usually <100 ng/L
  • folate deficient patients often have B12 levels at 100-200 ng/L
  • pregnant patients often have B12 levels at 100-200 ng/L
• dietary deficiency of vitamin B12 (very rare in the USA)
• pernicious anemia (gastric mucosal parietal cell intrinsic factor deficiency)
  • anti-parietal-cell antibodies (auto-antibody)
    • present in 90% of PA cases
    • present in atrophic gastritis which may or may not have yet lead to PA
  • anti-intrinsic-factor antibodies (auto-antibody) present in 75% of cases of PA
  • serum gastrin levels elevate with onset of parietal cell deficiency
• post-gastrectomy syndromes
• ileal mucosal deficiency situations (due to Crohn's-type inflammation or surgical removal)
• malabsorption syndromes
• microbe/parasitic competition syndromes (blind loop; fish tapeworm; etc.)
• R-binder (transcobalamin I or II & others) deficiency (causes a cobalamin pseudo-deficiency)
• high-dose intake of vitamin C without concomitant intake of B12 (too much C degrades B12)
• Orotic aciduria

NOTES:

• LDH elevation: because the bone marrow erythropoiesis is "ineffective" and with intramedullary hemolysis in vitamin B12 deficiency of any etiology, the serum LDH level is elevated, often strikingly so. But, concomitant iron deficiency exerts a hypoproliferative effect that retards the bulkiness of the B12 or folate deficient megaloblastic erythropoiesis, thereby retarding the quantity/rate of intramedullary hemolysis, which retards the LDH elevation.

• methylmalonic acid (MMA) elevations in serum and urine in:
  • chronic renal failure
  • vitamin B12 deficiency (regardless of etiology...nonspecific as to etiology) once the deficiency actually systemically causes metabolic consequences
• therapeutic trial: in a patient with macrocytic anemia likely to be due to B12 or folate deficit and not taking supplements or transfusion.......give a parenteral, physiological dose of B12 (10 micrograms IM/day) for several days, performing a periodic reticulocyte count which should peak in 5-7 days. The leuko-thrombocytopenia of B12 deficiency should return to normal in 7-10 days.

REFERENCES:

1. May 2001 LMC Lab internal memo
2. Interpretation of Diagnostic Tests, Wallach, 2000, 7th Ed.
3. ABC's of Interpretative Lab. Data, 2nd Ed., Seymour Bakerman, M. D., PhD. 1984

(posted 2000; latest update 24 March 2003)