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Methylmalonic Acid, Serum or Plasma

CPT: 83921
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Expected Turnaround Time

3 - 6 days

Specimen Requirements


Serum or plasma


2 mL

Minimum Volume

0.6 mL (Note: This volume does not allow for repeat testing.)


Red-top tube, gel-barrier tube, or green-top (heparin) tube


Separate serum or plasma from cells within one hour of collection.

Storage Instructions


Stability Requirements



Room temperature

14 days


14 days


19 days

Freeze/thaw cycles

Stable x3

Causes for Rejection

Plasma from a light blue-top or yellow-top tube; citrate interferes with assay

Test Details


Serum methylmalonic acid (MMA) measurement is used to evaluate individuals with signs and symptoms associated with vitamin B12 deficiency1-7 or congenital methylmalonic academia.8,9


This test was developed, and its performance characteristics determined, by LabCorp. It has not been cleared or approved by the US Food and Drug Administration (FDA).


Liquid chromatography/tandem mass spectrometry (LC/MS-MS)

Reference Interval

0−378 nmol/L

Additional Information

MMA is a four-carbon molecule that is a product of the metabolic break-down of valine, isoleucine, and propionic acid.1 Vitamin B12 is a critical cofactor for the conversion of MMA to succinate.1 As a result, vitamin B12 deficiency causes an accumulation of MMA in the serum.1 MMA concentrations will often become elevated in the early stages of vitamin B12 while serum vitamin B12 levels are in normal range.1-4 Consequently, MMA measurement is used as a diagnostic test for vitamin B12 deficiency in persons with a low or low normal serum vitamin B12 concentration.5,6 Follow-up measurement of MMA can also be of value in assessing the effectiveness of vitamin B12 supplementation of deficient patients.7

Vitamin B12 deficiency causes macrocytic anemias and decreased erythrocyte survival due to abnormal maturation of erythrocyte precursors in the bone marrow.10,11 Pernicious anemia is a form of vitamin B12 deficiency that is caused by a lack of intrinsic factor.10,11 Low vitamin B12 intake, gastrectomy, malabsorption, and transcobalamin deficiency can also cause vitamin B12 deficiency.10,11 Although severe vitamin B12 deficiency is associated with anemia, hematologic signs are not always observed in patients with biochemically confirmed deficiency.12 Elderly patients with cobalamin deficiency may present with peripheral neuropathy, ataxia, memory impairment, depression, and dementia in the absence of anemia.13,14

A generally agreed on cutoff for elevated plasma MMA is 370 nmol/L.6,12 Approximately 2% of the US population and 7% of elderly persons have MMA concentrations above this threshold.12


1. Klee GG. Cobalamin and folate evaluation: Measurement of methylmalonic acid and homocysteine vs vitamin B12 and folate. Clin Chem. 2000 Aug; 46(8 Pt 2):1277-1283. 10926922
2. Clarke R, Refsum H, Birks J, et al. Screening for vitamin B-12 and folate deficiency in older persons. Am J Clin Nutr. 2003 May; 77(5):1241-1247. 12716678
3. Savage DG, Lindenbaum J, Stabler SP, Allen RH. Sensitivity of serum methylmalonic acid and total homocysteine determinations for diagnosing cobalamin and folate deficiencies. Am J Med. 1994 Mar; 96(3):239-246. 8154512
4. Langan RC, Zawistoski KJ. Update on vitamin B12 deficiency. Am Fam Physician. 2011 Jun 15; 83(12):1425-1430. 21671542
5. Carmel R. Biomarkers of cobalamin (vitamin B-12) status in the epidemiologic setting: a critical overview of context, applications, and performance characteristics of cobalamin, methylmalonic acid, and holotranscobalamin II. Am J Clin Nutr. 2011 Jul; 94(1):348S-358S. 21593511
6. Hølleland G, Schneede J, Ueland PM, Lund PK, Refsum H, Sandberg S. Cobalamin deficiency in general practice. Assessment of the diagnostic utility and cost-benefit analysis of methylmalonic acid determination in relation to current diagnostic strategies. Clin Chem. 1999 Feb; 45(2):189-198. 9931040
7. Hoey PL, Strain JJ, McNulty H. Studies of biomarker responses to intervention with vitamin B-12: A systematic review of randomized controlled trials. Am J Clin Nutr. 2009 Jun; 89(6):1981S-1996S. 19403638
8. Tanpaiboon P. Methylmalonic acidemia (MMA). Mol Genet Metab. 2005 May; 85(1):2-6. 15959932
9. Fowler B, Leonard JV, Baumgartner MR. Causes of and diagnostic approach to methylmalonic acidurias. J Inherit Metab Dis. 2008 Jun; 31(3):350-360. 18563633
10. Hvas AM, Nexo E. Diagnosis and treatment of vitamin B12 deficiency- An update. Haematologica. 2006 Nov; 91(11):1506-1512. 17043022
11. Ryan-Harshman M, Aldoori W. Vitamin B12 and health. Can Fam Physician. 2008 Apr; 54(4):536-541. 18411381
12. Pfeiffer CM, Caudill SP, Gunter EW, Osterloh J, Sampson EJ. Biochemical indicators of B vitamin status in the US population after folic acid fortification: Results from the National Health and Nutrition Examination Survey 1999-2000. Am J Clin Nutr. 2005 Aug; 82920:442-450. 16087991
13. Selhub J, Morris MS, Jacques PF, Rosenberg IH. Folate-vitamin B-12 interaction in relation to cognitive impairment, anemia, and biochemical indicators of vitamin B-12 deficiency. Am J Clin Nutr. 2009 Feb; 89(2):702S-706S. 19141696
14. Tangney CC, Tang Y, Evans DA, Morris MC. Biochemical indicators of vitamin B12 and folate insufficiency and cognitive decline. Neurology. 2009 Jan 27; 72(4):361-367. 19171834


Vogiatzoglou A, Oulhaj A, Smith AD, et al. Determinants of plasma methylmalonic acid in a large population: implications for assessment of vitamin B12 status. Clin Chem. 2009 Dec; 55(12):2198-2206. 19833840


Order Code Order Code Name Order Loinc Result Code Result Code Name UofM Result LOINC
706961 Methylmalonic Acid, Serum 13964-2 706797 Methylmalonic Acid, Serum nmol/L 13964-2
706961 Methylmalonic Acid, Serum 13964-2 700480 Disclaimer: n/a

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