Methylmalonic acid (MMA) is a substance produced in the body during normal metabolism. The methylmalonic acid test is a laboratory tool used to measure the levels of this compound, typically in the blood or urine. Measuring these levels provides information about a person’s metabolic function and is most commonly used to determine certain nutritional statuses.
The Metabolic Role of Methylmalonic Acid
Methylmalonic acid is created as a byproduct during the breakdown of specific amino acids and fatty acids. This substance exists primarily as methylmalonyl coenzyme A (methylmalonyl-CoA). For the body to use this compound for energy, it must be converted into succinyl coenzyme A (succinyl-CoA), an intermediate molecule in the Krebs cycle.
This conversion requires the enzyme methylmalonyl-CoA mutase. The enzyme needs a cofactor, a form of vitamin B12 known as adenosylcobalamin, to function correctly. When functional vitamin B12 is sufficient, the conversion proceeds smoothly, and MMA levels remain low. If the B12 supply is inadequate, the conversion stalls, causing methylmalonyl-CoA to accumulate and convert into methylmalonic acid, which then builds up in the blood and urine.
Primary Clinical Application: Diagnosing Vitamin B12 Deficiency
Elevated levels of MMA indicate a functional vitamin B12 deficiency. Since the vitamin is directly required for the conversion of methylmalonyl-CoA, its scarcity leads to a direct and measurable metabolic consequence. This makes the MMA test a valuable tool, particularly when standard serum vitamin B12 levels are inconclusive or borderline.
The MMA test often detects deficiency earlier than a serum B12 test because it reflects B12 activity at the tissue level, not just the total amount circulating. Common symptoms prompting this testing include neurological issues like numbness or tingling, memory problems, and a specific form of anemia. A prompt diagnosis is important because B12 deficiency can lead to irreversible nerve damage if left untreated.
Understanding the Testing Procedure and Results
The methylmalonic acid test is typically performed on a blood sample, similar to a routine blood test, though a urine test may also be used. For a blood draw, a patient may sometimes be asked to fast for several hours beforehand to ensure accurate results.
The urine test may involve a single, random sample or a 24-hour collection. Normal serum MMA levels are generally under 0.40 micromoles per liter (µmol/L), though this range varies by laboratory. An elevated MMA level suggests a vitamin B12 deficiency, but a definitive diagnosis requires a physician to interpret results alongside the patient’s symptoms and other blood work. Treatment with vitamin B12 can quickly lower MMA levels, and follow-up testing confirms the intervention’s efficacy.
Other Causes of Elevated MMA
While vitamin B12 deficiency is the most common reason for elevated MMA, other conditions can also cause this buildup. The primary non-B12 cause is impaired kidney function. The kidneys are responsible for clearing MMA from the blood and excreting it through the urine.
If the kidneys are not working efficiently, MMA accumulates in the blood, leading to an elevated test result. Another factor is a group of rare inherited metabolic disorders known as methylmalonic acidemia. These genetic conditions involve a defect in the enzyme that processes MMA, causing extremely high levels often detected through newborn screening. Less common causes include small bowel bacterial overgrowth and certain medications.