Also Known As
MMA
This article was last reviewed on
This article waslast modified on December 6, 2019.
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?

When you have a low vitamin B12 level and/or have symptoms of B12 deficiency such as numbness, tingling in the hands or feet, trouble walking, swelling of body tissues, or yellowing of the skin or eyes; as part of newborn screening

Sample Required?

A blood sample drawn from a vein in your arm or from a heelstick in newborns; sometimes a random or 24-hour urine sample

Test Preparation Needed?

You may be instructed to fast before sample collection for this test.

You may be able to find your test results on your laboratory's website or patient portal. However, you are currently at Lab Tests Online. You may have been directed here by your lab's website in order to provide you with background information about the test(s) you had performed. You will need to return to your lab's website or portal, or contact your healthcare practitioner in order to obtain your test results.

Lab Tests Online is an award-winning patient education website offering information on laboratory tests. The content on the site, which has been reviewed by laboratory scientists and other medical professionals, provides general explanations of what results might mean for each test listed on the site, such as what a high or low value might suggest to your healthcare practitioner about your health or medical condition.

The reference ranges for your tests can be found on your laboratory report. They are typically found to the right of your results.

If you do not have your lab report, consult your healthcare provider or the laboratory that performed the test(s) to obtain the reference range.

Laboratory test results are not meaningful by themselves. Their meaning comes from comparison to reference ranges. Reference ranges are the values expected for a healthy person. They are sometimes called "normal" values. By comparing your test results with reference values, you and your healthcare provider can see if any of your test results fall outside the range of expected values. Values that are outside expected ranges can provide clues to help identify possible conditions or diseases.

While accuracy of laboratory testing has significantly evolved over the past few decades, some lab-to-lab variability can occur due to differences in testing equipment, chemical reagents, and techniques. This is a reason why so few reference ranges are provided on this site. It is important to know that you must use the range supplied by the laboratory that performed your test to evaluate whether your results are "within normal limits."

For more information, please read the article Reference Ranges and What They Mean.

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 cognitive impairment, 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 is 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 25,000 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 excessive tiredness, vomiting, dehydration, weak muscle tone, seizures, 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.

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.

See More
See Less
Common Questions
  • How is it used?

    The methylmalonic acid (MMA) test may be used to help diagnose an early or mild vitamin B12 deficiency. It may be ordered by itself or along with a homocysteine test as a follow-up to a vitamin B12 test result that is in the lower end of the normal range.

    MMA is a substance produced in very small amounts in the body. It is necessary for 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 level begins to rise, resulting in an increase of MMA in the blood and urine. Measuring methylmalonic acid in the blood or urine can help detect early vitamin B12 deficiency.

    There are currently no guidelines for screening asymptomatic adults for vitamin B12 deficiency, but confirmation with MMA and/or homocysteine may be necessary for those at high risk without symptoms, such as the elderly, or when certain medications have been taken for a long time.

    MMA is a very sensitive test in indicating a B12 deficiency. It is more specific than homocysteine and is the confirmatory test of choice for a B12 deficiency.

    Occasionally, specialized MMA testing may be ordered to help diagnose methylmalonic acidemia, a rare inherited metabolic disorder. Newborn screening programs in all 50 states in the U.S. now require testing for this disorder (see Newborn Screening).

  • When is it ordered?

    MMA is usually ordered, sometimes along with a homocysteine test, when a vitamin B12 test result is in the lower portion of the normal range, especially when a person has symptoms associated with B12 deficiency.

    Signs and symptoms of B12 deficiency may include:

    • Diarrhea
    • Dizziness
    • Fatigue, muscle weakness
    • Loss of appetite
    • Pale skin
    • Rapid heart rate, irregular heartbeats
    • Shortness of breath
    • Sore tongue and mouth
    • Tingling, numbness, and/or burning in the feet, hands, arms, and legs (with B12 deficiency)
    • Confusion or forgetfulness
    • Paranoia

    MMA is also ordered for asymptomatic adults who have a higher likelihood of having vitamin B12 deficiency, such as the elderly, or for those taking certain drugs, like Metformin, for a long time. An MMA test also may be ordered as a follow-up to an elevated homocysteine level if the two tests are not ordered together.

    MMA testing may be ordered when a health practitioner suspects that an acutely ill infant may have inherited methylmalonic acidemia.

  • What does the test result mean?

    If MMA and homocysteine levels are increased and the vitamin B12 level is mildly decreased, then an early or mild B12 deficiency may be present. This may indicate a decrease in available B12 at the tissue level.

    If only the homocysteine level is elevated and not MMA, then the person may have a folate deficiency. This distinction is important because giving folate to some who is B12-deficient will treat the anemia but does not treat the neurologic damage, which may be irreversible.

    If both MMA and homocysteine levels are normal, then it is unlikely that there is a B12 deficiency.

    Moderately to severely elevated levels of MMA may be seen in infants with the rare inherited disease methylmalonic acidemia.

    A decreased level of MMA is not common and is not considered clinically significant.

  • Is there anything else I should know?

    An elevated MMA test may indicate a B12 deficiency, but the amount of MMA measured does not necessarily reflect the severity of the deficiency, its likelihood of progressing, or the presence or severity of any symptoms.

    If an individual has kidney disease, he may have a falsely high level of MMA in his blood. If the kidneys are not functioning properly, they cannot properly eliminate MMA in the urine, causing MMA to accumulate in the blood.

    Some studies have found a high variation in MMA levels when they are measured over time.

  • If I have an elevated MMA, why might my doctor hesitate to diagnose me with vitamin B12 deficiency?

    If your B12 test result is in the lower end of the normal range and you do not present with significant clinical symptoms, your healthcare provider may feel that you have adequate B12 and will rely on these findings rather than an elevated MMA. This may be especially true if your homocysteine level is normal. Your healthcare provider may want to monitor your condition over time and may be reluctant to start you on what could be lifelong treatment with B12 injections and/or oral supplementation unless it is truly necessary.

  • Can either blood or urine be used for the MMA test?

    In most cases, it is okay to use blood or urine for this test. Sometimes, a healthcare provider may want to test both blood and urine in order to compare the MMA results. Since homocysteine is a blood test, it may be more efficient and convenient to draw blood for both the MMA and homocysteine tests when they are ordered together.

See More Common Questions See Less Common Questions
Related Content

On This Site

Tests: Vitamin B12 and Folate, Homocysteine, Intrinsic Factor Antibody, Complete Blood Count, Parietal Cell Antibody, Reticulocyte Count, Blood Smear

Conditions: Vitamin B12 and Folate Deficiency, Anemia
Screening: Newborns

Elsewhere On The Web

American Society of Hematology: Anemia 
National Institutes of Health, Office of Dietary Supplements: QuickFacts, Vitamin B12 
Mayo Clinic: Vitamin deficiency anemia 
Genetics Home Reference: Methylmalonic academia 

See More
See Less
View Sources

Sources Used in Current Review

2015 reviewer: Kristin Luckenbill, PhD, JD, DABCC, Clinical Chemist, Sanford Bismarck Laboratory.

Genome.gov. NIH National Human Genome Research Institute. Clinical and Basic Investigations of Methylmalonic Acidemia (MMA) and Related Disorders. Available online at http://www.genome.gov/19016900. Accessed September 2015.

Stabler, SP. Clinical Practice. Vitamin B12 Deficiency. N Engl J Med 2013; 368: 149-160.

Langan, RC and Zawistoski, KJ. Update on Vitamin B12 Deficiency. American Family Physician 2011; 83: 1425-1430.

Hunt, A. Vitamin B12 Deficiency. BMJ 2014. 349: 5226-5236 (Pubmed ID: 25189324).

Velente E, et al. Diagnostic Accuracy of Holotranscobalamin, Methylmalonic Acid, Serum Cobalamin, and Other Indicators of Tissue Vitamin B12 Status in the Elderly, Clinical Chemistry, June 2011 vol. 57 no. 6 856-863. Available online http://www.clinchem.org/content/57/6/856.full?sid=6adda730-c0e1-4006-ae9c-39c7b9ee27f9. Accessed September 2015.

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.

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.

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.

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. 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. 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. 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. 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. 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. Accessed November 2011.

See More
See Less

Ask a Laboratory Scientist

This form enables patients to ask specific questions about lab tests. Your questions will be answered by a laboratory scientist as part of a voluntary service provided by one of our partners, American Society for Clinical Laboratory Science. Please allow 2-3 business days for an email response from one of the volunteers on the Consumer Information Response Team.

Disclaimer
Thank you for using the Consumer Information Response Service ("the Service") to inquire about the meaning of your lab test results.  The Service is provided free of charge by the American Society for Clinical Laboratory Science, which is one of many laboratory organizations that supports Lab Tests Online.
Please note that information provided through this free Service is not intended to be medical advice and should not be relied on as such. Although the laboratory provides the largest single source of objective, scientific data on patient status, it is only one part of a complex biological picture of health or disease. As professional clinical laboratory scientists, our goal is to assist you in understanding the purpose of laboratory tests and the general meaning of your laboratory results. It is important that you communicate with your physician so that together you can integrate the pertinent information, such as age, ethnicity, health history, signs and symptoms, laboratory and other procedures (radiology, endoscopy, etc.), to determine your health status. The information provided through this Service is not intended to substitute for such consultations with your physician nor specific medical advice to your health condition.
By submitting your question to this Service, you agree to waive, release, and hold harmless the American Society for Clinical Laboratory Science and its affiliates or their past or present officers, directors, employees, agents, and Service volunteers (collectively referred to as "ASCLS") and the American Association  for Clinical Chemistry and its affiliates or their past or present officers, directors, employees, agents, and Service volunteers (collectively referred to as "AACC") from any legal claims, rights, or causes of action you may have in connection with the responses provided to the questions that you submit to the Service.
AACC, ASCLS and its Service volunteers disclaim any liability arising out of your use of this Service or for any adverse outcome from your use of the information provided by this Service for any reason, including but not limited to any misunderstanding or misinterpretation of the information provided through this Service.
 
See More See Less