From the Guidelines
Methylmalonic acid (MMA) is primarily checked to diagnose vitamin B12 deficiency, particularly when B12 blood levels are borderline or when there's clinical suspicion despite normal B12 levels. MMA levels rise when B12 is insufficient because B12 is required for converting methylmalonyl-CoA to succinyl-CoA; without adequate B12, methylmalonyl-CoA accumulates and is converted to methylmalonic acid 1. This test is more sensitive than serum B12 measurement alone and can detect functional B12 deficiency at an earlier stage.
Key Points to Consider
- MMA testing is especially valuable in elderly patients, vegetarians, those with gastrointestinal disorders affecting absorption, and patients taking medications like metformin or proton pump inhibitors that can interfere with B12 metabolism 1.
- When ordering this test, it's essential to note that kidney dysfunction can falsely elevate MMA levels, so renal function should be considered when interpreting results 1.
- If elevated MMA confirms B12 deficiency, treatment typically involves B12 supplementation, either orally or via intramuscular injection, depending on the severity and cause of the deficiency 1.
Diagnostic Approach
- A combination of at least two biomarkers (holo-transcobalamin and methylmalonic acid) is optimal for assessing cobalamin status 1.
- Serum cobalamin can be used as a replacement for holo-transcobalamin when measurement of the latter is unavailable 1.
- MMA levels can be quantified using various methods, including HPLC with fluorescence detection, gas chromatography coupled to mass spectrometry, and liquid chromatography tandem mass spectrometry 1.
From the Research
Reasons to Check Methylmalonic Acid
- Methylmalonic acid (MMA) is a useful marker for diagnosing vitamin B12 deficiency, particularly in asymptomatic high-risk patients with low-normal levels of vitamin B12 2
- Elevated MMA concentrations are more strongly associated with poor functional status and physical performance than serum B12 levels 3
- Measuring MMA is necessary for the diagnosis of metabolic vitamin B12 deficiency, as serum B12 alone is not sufficient 4
- MMA is considered the best biomarker for detecting possible vitamin B12 deficiency, and establishing reference intervals for MMA in urine can help improve diagnosis 5
- Vitamin B12 deficiency can have severe consequences, including megaloblastic anemia, nervous system involvement, and cognitive impairment, making accurate diagnosis and treatment crucial 6
Clinical Applications
- Checking MMA levels can help confirm vitamin B12 deficiency in patients with low-normal vitamin B12 levels 2
- MMA measurements can be used to assess the effectiveness of vitamin B12 treatment and monitor patients with a history of vitamin B12 deficiency 3
- MMA testing can help identify patients with metabolic vitamin B12 deficiency, who may benefit from supplementation with oral B12, preferably methylcobalamin or hydroxycobalamin 4
- Establishing optimal reference intervals for MMA excretion in urine can aid in the diagnosis of functional vitamin B12 deficiency 5
- Accurate diagnosis and treatment of vitamin B12 deficiency can help prevent severe consequences, such as cognitive impairment and psychosis 6