Laboratory diagnosis of B12 deficiency

 -A blood count showing the presence of a high mean corpuscular volume (MCV) may alert the physician to the presence of cobalamin deficiency.

- Folate deficiency may lead to falsely low cobalamin levels.

- In cases with a suspicious clinical picture and hematological alteration, but the serum cobalamin level is undetermined, the measurement of plasma homocysteine (normal 5-15 umol/L) and elevated plasma methyl malonate -MMA (normal <0.28 umol/L, very specific) can be considered as complementary tests because they are functional markers of the Cbls status in the organism.

- Holotranscobalamin is the form of Cbls absorbed by cells to meet metabolic demand and laboratory testshave recently become available.

- The presence of anti-intrinsic factor antibodies and anti-parietal cell antibodies should be investigated when there is no apparent cause for very low Cbls levels and may be present in pernicious anemia that can influence the results of tests based on competitive binding luminescence technologies, making the diagnosis of Cbls deficiency difficult. - Renal failure and the presence of inborn errors of metabolism may interfere with the measurement of MMA and homocysteine, respectively.

- Increased homocysteine is less specific, as it also  increases in cases of folate deficiency, vitamin B6 deficiency, and hypothyroidism. They are very useful when there is a clinical picture suggestive of Cbls deficiency but with normal levels. Falsely normal borderline levels may occur in chronic liver disease or  myeloproliferative diseases.

- For patients with borderline cobalamin concentrations (between 200 and 300 pg/mL), the interpretation of additional deficiency markers is recommended. The main marker used in these situations is MMA. MMA is an intermediate metabolite that accumulates in cases of cobalamin deficiency, presenting an increase in its concentration. The same occurs with homocysteine. However, homocysteine can also increase in cases of folate deficiency, unlike MMA.

- Elevated homocysteine levels may be observed in patients with arterial thrombosis resulting fromatherosclerotic disease, and in individuals with venous thromboembolism. These levels are usually normalized only with the administration of folic acid, so I rarely need to use B complex in this clinical situation. Unfortunately, normalization of homocysteinemia is not associated with a reduction in the frequency of recurrence of venous thrombosis.

    Serum cobalamin levels should be monitored periodically, including folate, iron, hematocrit, and reticulocyte counts. Homocysteine and MMA levels may be useful. Platelet pool and potassium levels should also be monitored during cobalamin therapy. Serial follow-up should be 2 to 6 months, depending on the clinical picture.

Reference

DOI: https://doi.org/10.54448/ijn25103