비타민 B12 결핍 거대적아구성 빈혈 진단을 위한 Methylmalonic Acid 검사의 유용성

Abstract

Background: Methylmalonic acid (MMA) is one of the metabolites of the DNA synthesis metabolic pathway wherein vitamin B12 acts as a coenzyme. Vitamin B12 deficiency leads to inhibition of methylmalonyl CoA mutase, and sequential elevation of blood and urine concentrations of MMA. It has been known that the urine concentration of MMA is a more specific and sensitive marker than the hematologic indices and the serum concentration of vitamin B12 for the diagnosis of vitamin B12 deficiency. We investigated the sensitivity of urine concentration of MMA and the usefulness as a differential marker for myelodysplastic syndrome (MDS) and megaloblastic anemia (MA).

Methods: We identified 37 cases that were examined for both urine concentrations of MMA and bone marrow studies from January 1996 to December 2000. Serum concentrations of vitamin B12 and folate were measured by the chemiluminescence immunoassay using ACS:180 (Bayer Diagnostics). Urine concentration of MMA was measured by isotope dilution gas chromatography-mass spectrometry (GC 8000-gas chromatography MD800).

Results: Of 36 patients, 12 patients were diagnosed with MA, 8 patients with MDS, 5 patients with aplastic anemia based on the bone marrow study. Increased urine concentration of MMA was observed in all the patients with MA, but none of the patients with MDS. Using a cut-off value of 5 m㏖/㏖ creatinine urine concentration MMA, the sensitivity and specificity in diagnosis for MA were 100% and 80%. The correlation between the urine concentration of MMA and the serum concentration of vitamin B12 was insignificant (r=-0.25, P=0.21). The highest correlation index with urine concentration of MMA was the red cell distribution width (r=0.74, P<0.01).

Conclusions: We concluded that the urine concentration of MMA was a sensitive marker for diagnosis of MA caused by vitamin B12 deficiency and could be a useful test in the differentiation for MA from MDS. Although a consensus for a diagnostic value of the urine concentration of MMA would be necessary, we recommend using both the urine concentration of MMA and the serum vitamin B12 as primary tests for diagnosis of MA caused by vitamin B12 deficiency.