To help detect vitamin B12 deficiency when results of Vitamin B12 testing are equivocal and there is a high clinical suspicion of deficiency; to help diagnose methylmalonic acidaemia, a rare inherited metabolic disorder
If you have a vitamin B12 concentration in the low end of the normal range and/or unexplained symptoms of neuropathy, such as numbness and tingling in the hands and feet or unexplained macrocytosis (large blood cells)
You may be instructed to fast before sample collection for this test.
Methylmalonic acid (MMA) is a compound produced in very small amounts during amino acid metabolism. Increased production of MMA occurs in vitamin B12 deficiency. This is because vitamin B12 acts as a coenzyme, promoting the conversion of methylmalonyl CoA to succinyl CoA. If there is not enough B12 available to act as a coenzyme, methylmalonyl CoA concentrations begin to rise and the body converts the methylmalonyl CoA to MMA instead. Measurement of MMA in either urine or blood is therefore a sensitive marker of Vitamin B12 deficiency.
Increased production of MMA in newborn babies may suggest one of the inherited problems collectively called the methylmalonic acidaemias. Babies with this disease are unable to convert methylmalonyl CoA to succinyl CoA and therefore increased production of MMA is observed.
How is the sample collected for testing?
Is any test preparation needed to ensure the quality of the sample?
You may be instructed to fast before sample collection for this test. Please follow any instructions that you are given.
How is it used?
Vitamin B12 analysis is available routinely and in the majority of cases the vitamin B12 test will be sufficient to assess for deficiency. However, MMA should be measured in cases where there is a high suspicion of vitamin B12 deficiency yet the vitamin B12 result is equivocal. It is important to detect vitamin B12 deficiency as it can cause a decrease in the number of red blood cells (anaemia) and changes to bone marrow function. It can also cause signs and symptoms of disease, inflammation or damage to the peripheral nerves (neuropathy), such as numbness and tingling in the hands and feet and/or mental or behavioural changes (confusion, irritability, depression).
Some researchers have suggested using MMA as a screening tool especially among the elderly who frequently have vitamin B12 deficiencies and may have few recognisable symptoms. However, this use is still controversial in the medical community and only a few doctors are using MMA for this purpose.
Occasionally, specialised MMA testing may be requested to help diagnose methylmalonic acidaemias, a rare inherited metabolic disorder that occurs in about 1 in 50,000 to 100,000 people. Babies with this disease are unable to convert methylmalonyl CoA to succinyl CoA. They appear normal at birth but as they ingest protein, they begin to show symptoms such as seizures, failure to thrive, mental retardation, strokes, and severe metabolic acidosis. Often the presence of methylmalonic acid will be assessed as part of a wider screen for inherited metabolic disorders.
When is it requested?
Methylmalonic acid is not requested frequently. Until there are more data supporting its use and consensus on its clinical utility and long-term benefits, it will probably not be routinely used by doctors.
However, MMA may be requested, sometimes along with a homocysteine test, when a vitamin B12 test result is equivacol but there is a high suspicion of vitamin B12 deficiency in a patient. An MMA test also may be requested as a follow-up to an elevated homocysteine result if the two tests are not requested together. An MMA test also may be requested as a follow-up to an elevated homocysteine result if the two tests are not requested together.
Occasionally, specialised MMA testing may be requested when a doctor suspects that an acutely ill infant may have inherited methylmalonic acidaemia.
What does the test result mean?
If MMA and homocysteine levels are increased and B12 concentrations are 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 homocysteine levels are elevated, then folate concentrations should be checked). If MMA and homocysteine levels are normal, it is unlikely that there is a B12 deficiency.
Since the test for MMA is usually requested to detect elevated levels in suspected cases of B12 deficiency, decreased levels of MMA are not clinically significant.
Blood MMA levels also can be increased with kidney disease, which results in decreased MMA excretion in the urine, so MMA accumulates in the blood.
Moderately to severely elevated levels of MMA may be seen in infants with the rare inherited disease methylmalonic acidaemia.
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.
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 have significant symptoms, your doctor may feel that you have adequate B12 and will rely on these findings rather than on the elevated MMA. This may be especially true if your homocysteine level is normal. Your doctor may want to monitor your condition over time. He may be reluctant to start you on what could be lifelong treatment with B12 injections and/or oral supplementation unless he feels 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. Since homocysteine is a blood test, it may be more efficient to collect blood for both the MMA and homocysteine tests when they are requested together.