In examining the relationship of serum vitamin B12 levels to homocysteine levels,1 Julie Robertson and colleagues highlight the utility of homocysteine in the clinical investigation of vitamin B12 deficiency.
Both methylmalonic acid and homocysteine are elevated in vitamin B12 deficiency. The measurement of methylmalonic acid requires not readily available methods involving mass spectrometry, whereas homocysteine is readily measured in the clinical laboratory by fluorescent polarization, enzymatic assays and high-pressure liquid chromatography. There is a strong correlation between methylmalonic acid and homocysteine levels, and the sensitivity of homocysteine levels for identifying vitamin B12 deficiency is greater than 95%.2,3,4 Measurement of creatinine, folate and vitamin B12 levels and the patient's response to treatment will clarify the cause of the elevated homocysteine levels. At my institution we no longer routinely offer methylmalonic acid measurement as the diagnostic efficiencies of methylmalonic acid and homocysteine seem similar for the identification of a functional vitamin B12 deficiency.
Robertson and associates state that 17.3% of their population (73/421 cases) had a vitamin B12 deficiency. Of the 50 patients in whom methylmalonic acid was measured, 59% had elevated methylmalonic acid levels, confirming a functional vitamin B12 deficiency. It would have been interesting to know what the homocysteine levels were in these 73 subjects and to conduct a receiver–operator curve analysis to determine the efficiency of methylmalonic acid and homocysteine for identifying vitamin B12 deficiency. If all the patients with elevated methylmalonic acid levels also had elevated homocysteine levels, this would support the idea that homocysteine alone (without methylmalonic acid) can be used to assess vitamin B12deficiency and its response to treatment.
Brian M. Gilfix Associate Physician Division of Clinical Biochemistry Royal Victoria Hospital Montréal, Que.
REFERENCES
- 1.Robertson J, Iemolo F, Stabler SP, et al. Vitamin B12, homocysteine and carotid plaque in the era of folic acid fortification of enriched cereal grain products. CMAJ 2005;172(12):1569-73. [DOI] [PMC free article] [PubMed]
- 2.Holleland G, Schneede J, Ueland PM, et al. Cobalamin deficiency in general practice. Assessment of the diagnostic utility and cost-benefit analysis of methylmalonic acid determinations in relation to current diagnostic strategies. Clin Chem 1999;45(2):189-98. [PubMed]
- 3.Refsum H, Smith AD, Ueland PM, et al. Facts and recommendations about total plasma homocysteine determinations: an expert opinion. Clin Chem 2004;50(1):3-32. [DOI] [PubMed]
- 4.Savage DG, Lindebaum J, Stabler SP, et al. Sensitivity of serum methylmalonic acid and total homocysteine determinations for diagnosing cobalamin deficiencies. Am J Med 1994;96:239-46. [DOI] [PubMed]