To help detect early and/or mild vitamin B12 deficiency; sometimes to help diagnose newborns with methylmalonic acidemia, a rare inherited metabolic disorder
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 (see Common Questions)
A blood sample is obtained by inserting a needle into a vein in your 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.
Fasting is typically required for the blood test. For a random urine sample, you should fast overnight, discard the first urine sample of the morning, and then collect the second sample.
Methylmalonic acid (MMA) is a substance produced in very small amounts and is necessary for human metabolism and energy production. This test measures the level of MMA in blood or sometimes urine.
Vitamin B12 is responsible for two critical enzymatic reactions that promote cell metabolism. B12 promotes the conversion of methylmalonyl CoA (a form of MMA) to succinyl Coenzyme A, and with folic acid, aids in converting homocysteine to methionne.
Blood and/or urine levels of MMA rise when your B12 level begins to decrease. The measurement of elevated amounts of methylmalonic acid in the blood or urine serves as a sensitive and early indicator of vitamin B12 deficiency.
A B12 deficiency can occur when your nutrition intake is poor or you have gastrointestinal malabsorption issues. 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 even before B12 levels abnormally decrease, presence of blood cell changes, and/or 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 usefulness. 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.
The methylmalonic acid (MMA) test may be used to help diagnose an early or mild vitamin B12 deficiency. It may be ordered by itself but generally with a homocysteine test as a follow-up to a vitamin B12 test result that is in the lower end of the normal range.
There are currently no official guidelines for screening for average-risk adults. Testing may be warranted for asymptomatic adults with one or more risk factors, such as when you are elderly with inconsistent nutrition practices, in alcoholics, strict vegans/vegetarians, or when you have taken certain drugs, like Metformin, proton pump inhibitors, or H2 receptor antagonists for a long time. Also, cancer patients who have gastrointestinal malabsorption problems, have a poor dietary intake, or have had certain surgeries may be tested for B12 deficiency. In general, confirmation tests for MMA and/or homocysteine may be necessary to establish a diagnosis of B12 deficiency. 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.
MMA is usually ordered, sometimes along with a homocysteine test, when your vitamin B12 test result is in the lower portion of the normal range, especially when you have symptoms associated with B12 deficiency, or if one or more risk factors are present.
Signs and symptoms of B12 deficiency may include:
If your MMA and homocysteine levels are increased and your vitamin B12 level is mildly decreased, then an early or mild B12 deficiency may be present. This may indicate a decrease in your available B12 at the tissue level.
If only your homocysteine level is elevated and not MMA, then you may have a folate deficiency. This distinction is important because giving folate to someone who is B12-deficient will treat the anemia but does not treat the neurologic damage, which may be irreversible.
If both your MMA and homocysteine levels are normal, then it is unlikely that you have a B12 deficiency.
A decreased level of MMA is not common and is not considered clinically significant.
Occasionally, specialized MMA testing may be ordered to help diagnose methylmalonic acidemia. Moderately to severely elevated levels of MMA may be seen in infants with the rare inherited metabolic disorder methylmalonic acidemia, caused by genetic mutations of chromosome 6.
An acutely ill infant with methylmalonic acidemia who shows sepsis, poor feeding, lethargy, and vomiting may progress to coma and death if not promptly treated. Laboratory testing for ketones, lactic acid, ammonia, hypoglycemia, decreased blood cell counts, and elevated C3 acylcarnitines and organic acids in the urine may be done. MMA testing may also be ordered.
Methylmalonic acidemia occurs in about 1 in 25,000 to 100,000 newborns. 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 information, see the Newborn Screening article.
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.
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.
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 you have kidney disease, you may have a high level of MMA in your blood. If your 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.
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