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 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.
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.