Methylmalonic Acid

MMA is primarily requested, sometimes along with homocysteine, to help diagnose vitamin B12 deficiency, when results of vitamin B12 analysis are equivocal.

Vitamin B12 analysis is available routinely and in majority of cases will be sufficient to assess for deficiency. 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 peripheral neuropathy (damage to the nerves in the arms and legs, leading to numbness and tingling in the hands and feet), glossitis (inflammation of the tongue), and/or mental or behavioural changes (confusion, irritability, depression).

Occasionally, MMA measurement may be requested to help diagnose methylmalonic acidaemia, 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 MMA will be assessed as part of a wider screen for inherited metabolic disorders.

MMA is not often required. Until there is more data supporting its use and consensus on its clinical utility and long-term benefits, it will probably not be routinely used by doctors.

MMA may be requested, sometimes along with a homocysteine test, when a vitamin B12 result is equivocal, but there is a high suspicion of vitamin B12 deficiency in a patient, such as heavy recreational user of nitrous oxide. Nitrous oxide (laughing gas), a colourless gas commonly used as a painkiller, is increasingly being taken as a recreational drug. Intensive and frequent use of nitrous oxide inactivates vitamin B12, which means that vitamin B12 is not available to be utilised by the body. This can lead to a functional deficiency of vitamin B12, resulting in neurological damage, even if blood tests for vitamin B12 appear normal.

An MMA test may be requested as a follow-up to an elevated homocysteine result if the two tests were not requested together.

Occasionally, MMA testing may be requested when a doctor suspects that an acutely ill infant may have inherited methylmalonic acidaemia.

If MMA and homocysteine concentration 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, vitamin B12 deficiency is unlikely.

Since MMA is requested to detect elevated levels in suspected cases of vitamin B12 deficiency or to investigate for methylmalonic academia, decreased levels of MMA are not clinically significant.

Blood MMA concentration can also be increased with kidney disease, which results in decreased MMA excretion in the urine and accumulation in the blood. Other conditions, which cause elevated MMA levels in the blood, are small bowel bacterial overgrowth or dehydration.

An elevated MMA test may indicate a vitamin 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 your vitamin B12 test result is at the low end of the normal range and you do not have significant symptoms, your doctor may feel that you have adequate vitamin B12 and will rely on these findings rather than the elevated MMA. This may be especially true if your homocysteine level is normal. Your doctor may want to monitor your condition over time and response to dietary, or other medication, changes.