At a Glance
Why Get Tested?
To help detect early and/or mild vitamin B12 deficiency; to help diagnose methylmalonic acidemia, a rare inherited metabolic disorder
When to Get Tested?
Test Preparation Needed?
You may be instructed to fast before sample collection for this test.
The Test Sample
What is being tested?
Methylmalonic acid (MMA) is a substance produced in very small amounts and is necessary for human metabolism and energy production. In one step of metabolism, vitamin B12 promotes the conversion of methylmalonyl CoA (a form of MMA) to succinyl Coenzyme A. If there is not enough B12 available, then the MMA concentration begins to rise, resulting in an increase of MMA in the blood and urine. The measurement of elevated amounts of methylmalonic acid in the blood or urine serves as a sensitive and early indicator of vitamin B12 deficiency.
Over time, vitamin B12 deficiency can cause blood cell changes, leading to anemia and the production of large red blood cells (macrocytes). It can also cause signs and symptoms of neuropathy, such as numbness and tingling in the hands and feet and/or, in advanced cases, mental or behavioral changes such as confusion, irritability, and depression. An increased concentration of MMA is often detectable before blood cell changes and before full-blown symptoms are apparent, though some people may have some degree of neuropathy.
The relationship between MMA and B12 has been known for over 40 years, but the use of MMA testing is not widespread nor is there agreement on its clinical utility. Because a relatively large amount of the B12 found in the blood is bound to proteins and is not biologically active, some in the medical community think that MMA may be a better measure of bioavailable B12 than the usual vitamin B12 test. Others believe that MMA and homocysteine (which may also be elevated when either B12 or folate are deficient) are valuable in detecting early and mild cases of B12 deficiency. Still others argue that many of the mild deficiencies detected do not progress to more severe deficiencies and do not necessarily need to be identified or treated.
Testing newborns for high levels of MMA may help diagnose methylmalonic acidemia, a rare metabolic disorder that occurs in about 1 in 50,000 to 100,000 people. Screening for this disorder is part of mandatory programs in all 50 states in the U.S. Babies with this disease are unable to convert methylmalonyl CoA to succinyl CoA. They appear normal at birth, but as they consume protein, they begin to show symptoms such as seizures, failure to thrive, mental retardation, strokes, and severe metabolic acidosis. For more, see the newborn screening article.
How is the sample collected for testing?
A blood sample is obtained by inserting a needle into a vein in the arm. For newborns, blood may be collected from a heelstick. A single random urine sample may be collected (the second morning sample is preferred) or a 24-hour collection of urine may be requested.
NOTE: If undergoing medical tests makes you or someone you care for anxious, embarrassed, or even difficult to manage, you might consider reading one or more of the following articles: Coping with Test Pain, Discomfort, and Anxiety, Tips on Blood Testing, Tips to Help Children through Their Medical Tests, and Tips to Help the Elderly through Their Medical Tests.
Another article, Follow That Sample, provides a glimpse at the collection and processing of a blood sample and throat culture.
Is any test preparation needed to ensure the quality of the sample?
Fasting is typically required for the MMA blood test. For a random urine sample, the person being tested should fast overnight, discard the first urine sample of the morning, and then collect the second sample.
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NOTE: This article is based on research that utilizes the sources cited here as well as the collective experience of the Lab Tests Online Editorial Review Board. This article is periodically reviewed by the Editorial Board and may be updated as a result of the review. Any new sources cited will be added to the list and distinguished from the original sources used.
Sources Used in Current Review
Mandava, P. and Kent, T. (Updated 2011 March 29). Methylmalonic Acidemia. Medscape Reference [On-line information]. Available online at http://emedicine.medscape.com/article/1161799-overview through http://emedicine.medscape.com. Accessed November 2011.
Dugdale, D. (Updated 2010 February 1). Pernicious anemia. MedlinePlus Medical Encyclopedia [On-line information]. Available online at http://www.nlm.nih.gov/medlineplus/ency/article/000569.htm. Accessed November 2011.
(© 1995-2011). Unit Code 80289: Methylmalonic Acid (MMA), Quantitative, Serum. Mayo Clinic Mayo Medical Laboratories [On-line information]. Available online at http://www.mayomedicallaboratories.com/test-catalog/Overview/80289 through http://www.mayomedicallaboratories.com. Accessed November 2011.
Frank, E. et. al. (Updated 2010 September). Megaloblastic Anemia. ARUP Consult [On-line information]. Available online at http://www.arupconsult.com/Topics/MegaloblasticAnemia.html?client_ID=LTD#tabs=0 through http://www.arupconsult.com. Accessed November 2011.
Bodamer, O. and Lee, B. (Updated 2011 September 14). Genetics of Methylmalonic Acidemia. Medscape Reference [On-line information]. Available online at http://emedicine.medscape.com/article/947154-overview through http://emedicine.medscape.com. Accessed November 2011.
Dugdale, D. (Updated 2009 November 15). Methylmalonic acid test. MedlinePlus Medical Encyclopedia [On-line information]. Available online at http://www.nlm.nih.gov/medlineplus/ency/article/003565.htm. Accessed November 2011.
Wu, A. (© 2006). Tietz Clinical Guide to Laboratory Tests. 4th Edition: Saunders Elsevier, St. Louis, MO. Pp 740-741.
Harmening D. Clinical Hematology and Fundamentals of Hemostasis. Fifth Edition, F.A. Davis Company, Philadelphia, 2009, Pg 149.
(Oct. 5, 2011) National Newborn Screening and Genetic Resource Center. National Newborn Screening Status Report. Available online at http://genes-r-us.uthscsa.edu/nbsdisorders.htm through http://genes-r-us.uthscsa.edu. Accessed November 2011.
Ueland PM, Schneede J. Measurement of methylmalonic acid, homocysteine and methionine in cobalamin and folate deficiencies and homocysteinuria. Pubmed online. Available online at http://www.ncbi.nlm.nih.gov/pubmed/18337849 through http://www.ncbi.nlm.nih.gov. Accessed November 2011.
Sources Used in Previous Reviews
Clarke, W. and Dufour, D. R., Editors (2006). Contemporary Practice in Clinical Chemistry, AACC Press, Washington, DC. Pp 406.
Wu, A. (2006). Tietz Clinical Guide to Laboratory Tests, Fourth Edition. Saunders Elsevier, St. Louis, Missouri. Pp 740-741.
Greco, F. (2007 October 15). Methylmalonic acid test. MedlinePlus Medical Encyclopedia [On-line information]. Available online at http://www.nlm.nih.gov/medlineplus/ency/article/003565.htm. Accessed on 2/17/08.
Hurd, R. (2007 April 26, Updated). Methylmalonic acidemia. MedlinePlus Medical Encyclopedia [On-line information]. Available online at http://www.nlm.nih.gov/medlineplus/ency/article/001162.htm. Accessed on 2/17/08.
(2008 January, Reviewed). Methylmalonic acidemia. Genetics Home Reference [On-line information]. Available online through http://ghr.nlm.nih.gov. Accessed on 2/17/08.
Grund, S. (2007 August 27). Pernicious anemia. MedlinePlus Medical Encyclopedia [On-line information]. Available online at http://www.nlm.nih.gov/medlineplus/ency/article/000569.htm. Accessed on 2/17/08.
Venditti, C. (2007 January 18, Revised). Methylmalonic acidemia. GeneReviews [On-line information]. Available online through http://www.genetests.org. Accessed on 2/24/08.
Thomas, Clayton L., Editor (1997). Tabers Cyclopedic Medical Dictionary. F.A. Davis Company, Philadelphia, PA [18th Edition].
Pagana, Kathleen D. & Pagana, Timothy J. (2001). Mosbys Diagnostic and Laboratory Test Reference 5th Edition: Mosby, Inc., Saint Louis, MO.
Klee, G. (2000). Cobalamin and Folate Evaluation: Measurement of Methylmalonic Acid and Homocysteine vs Vitamin B12 and Folate. Clinical Chemistry. 46:1277-1283 [Abstract]. Available online at http://www.clinchem.org/cgi/content/abstract/46/8/1277 through http://www.clinchem.org.
Oh, R. and Brown, D. (2003 March 1). Vitamin B12 Deficiency. American Family Physician [On-line journal]. Available online at http://www.aafp.org/afp/20030301/979.html through http://www.aafp.org.
Elin, R. and Winter, W. (2001 January 18). Methylmalonic Acid, A Test Whose Time Has Come? Archives of Pathology and Laboratory Medicine Vol. 125, No. 6, pp. 824827. [On-line journal]. Available online through http://arpa.allenpress.com.
Hvas, A., et. al. (2001 June 25). Increased Plasma Methylmalonic Acid Level Does Not Predict Clinical Manifestations of Vitamin B12 Deficiency. Arch Intern Med vol 161.
Smith, D. (2000 October 1). Anemia in the Elderly. American Family Physician [On-line journal]. Available online at http://www.aafp.org/afp/20001001/1565.html through http://www.aafp.org.