Assessment of the Diagnostic Utility of Methylmalonic Acid in Megaloblastic Anemia due to Vitamin B12 Deficiency

Kong, Sun Young; Nam, Myung Hyun; Woo, Hee Yeon; Lee, Soo Yeon; Lee, Kyung A; Kim, Jong Won; Kim, Sun Hee

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 methyl-malonyl 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 hema-tologic 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 mark-er 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 Diag-nostics). 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 mmol/mol 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 con-centration 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 diagno-sis 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 nec-essary, we recommend using both the urine concentration of MMA and the serum vitamin B12 as prima-ry tests for diagnosis of MA caused by vitamin B12 deficiency.