Methylmalonic acid is one of those medical trivia blood tests that is ordered only occasionally in the primary care physician’s office. It is not especially useful as a screening test because of it’s very low specificity. Its primary use is to confirm vitamin B12 deficiency in a patient who is found to have a borderline low vitamin B12 blood level.
Methylmalonic acid is a precursor to the production of succinyl-CoA which is a key part of the Kreb’s cycle. Anyone who has studied biochemistry cringes when they hear the words “Kreb’s Cycle” because memorization and understanding of this process is the key to understanding human metabolism and energy production. The step of enzymatic conversion of the Methylmalonic –CoA into succinyl-CoA requires vitamin B12, and as a result methylmalonic acid levels are reliably elevated in patients with vitamin B12 deficiency.
Vitamin B12 deficiency is fairly common and often serious disorder which can lead to nerve damage, both to peripheral nerves and in the central nervous system. B12 deficiency is one of the causes of peripheral neuropathy. After diabetes and idiopathic peripheral neuropathy it is generally considered to be the third most common cause of this loss of function of the longest nerves in the body. Symptoms of peripheral neuropathy include numbness and tingling of the feet and legs. Later in the course it can also affect the hands.
When a physician finds a patient has level of vitamin B12 in the low normal or slightly reduced range, they often order a methylmalonic acid level. This is just a blood test, and it is quite sensitive for B12 deficiency. Over 90% of patients with B12 deficiency have elevated levels of methylmalonic acid, and a low or normal level makes B12 deficiency very unlikely.
The test is not useful as an initial test for B12 deficiency because up to 25% of adults over age 70 may have elevated levels of methylmalonic acid, and many of them do not have low levels of vitamin B12.
The specificity of a test is the chances that a person with a positive test has the disorder being tested for. The sensitivity is the chances of a person with a disorder having a positive test. They are expressed mathematically as follows: