From the Guidelines
A methylmalonic acid (MMA) test is a confirmatory test for vitamin B12 deficiency, particularly useful when initial test results are in an indeterminate range, as it provides a more reliable diagnosis that reflects the functional status of vitamin B12. This test measures the level of methylmalonic acid in the body, which builds up when vitamin B12 levels are low, and is more sensitive than standard B12 blood tests 1. The MMA test is especially valuable for diagnosing B12 deficiency in patients with neurological symptoms, elderly patients, vegetarians, or those with gastrointestinal disorders affecting absorption. Some key points to consider about the MMA test include:
- It is not suitable as a first-line test due to its high cost (£11-80) and the need for specialist analytical equipment 1
- The test can detect early or subtle B12 deficiencies that might otherwise be missed
- Elevated MMA levels strongly suggest a B12 deficiency, even when serum B12 levels appear normal
- The test is useful for monitoring the effectiveness of B12 supplementation therapy
- No special preparation is typically needed before the test, though fasting may be required in some cases.
From the Research
Methylmalonic Acid Test
The methylmalonic acid (MMA) test is a diagnostic tool used to assess vitamin B12 status and deficiency.
- It measures the levels of methylmalonic acid in the blood or urine, which is a metabolite that accumulates when vitamin B12 is deficient 2, 3, 4, 5, 6.
- Elevated concentrations of MMA are considered a representative marker of metabolic vitamin B12 insufficiency 3.
- The test is often used in conjunction with other markers, such as holotranscobalamin (holoTC), homocysteine, and total vitamin B12, to confirm a diagnosis of vitamin B12 deficiency 2, 3, 4, 5, 6.
Methods of Measurement
There are different methods for measuring MMA, including:
- Gas chromatography mass spectrometry (GCMS) 2
- Liquid chromatography tandem mass spectrometry (LC-MS/MS) 2
- These methods have been compared and shown to have strong correlations, with LC-MS/MS offering advantages such as saving time and costs, precision, flexibility, and popularity in modern labs 2.
Clinical Applications
The MMA test has several clinical applications, including:
- Diagnosing vitamin B12 deficiency in patients with symptoms such as megaloblastic anemia, neuropsychiatric symptoms, and other clinical manifestations 4
- Screening high-risk patients, such as those with gastric or small intestine resections, inflammatory bowel disease, or taking certain medications 4
- Monitoring the effectiveness of vitamin B12 supplementation 4
- Identifying patients with elevated MMA concentrations, which are associated with poor functional status and physical performance 5.