In B12 deficiency, what happens to the level of methylmalonic acid (MMA)?

In vitamin B12 deficiency, methylmalonic acid (MMA) levels become elevated due to the impaired conversion of methylmalonyl-CoA to succinyl-CoA. This conversion is dependent on vitamin B12, specifically the form known as methylcobalamin, which acts as a cofactor for the enzyme methylmalonyl-CoA mutase. When vitamin B12 is deficient, this enzymatic reaction is hindered, leading to a buildup of methylmalonyl-CoA, which subsequently increases the production of MMA.

Elevated MMA is a key laboratory finding that can help differentiate vitamin B12 deficiency from other causes of megaloblastic anemia, such as folate deficiency. While folate deficiency also leads to megaloblastic changes, it does not affect MMA levels, as its metabolism is independent of vitamin B12. Therefore, the presence of elevated MMA can serve as an important diagnostic marker for vitamin B12 deficiency and is clinically significant in the evaluation of patients with anemia and neurological symptoms associated with this condition.