Methylmalonic acid (MMA) is a metabolic byproduct whose levels can indicate metabolic health. Elevated MMA levels, often found during routine blood tests, signal a need for further investigation to uncover the underlying cause. Understanding what this elevation signifies is important for proper diagnosis and management.
What is Methylmalonic Acid?
Methylmalonic acid (MMA) is a metabolic byproduct formed during the breakdown of fats and proteins, including certain amino acids and odd-chain fatty acids. To process and eliminate MMA, the body requires the enzyme methylmalonyl-CoA mutase. This enzyme relies on Vitamin B12 as a cofactor to convert methylmalonyl-CoA into succinyl-CoA, which then enters energy production pathways. In healthy individuals, MMA is present in very small amounts, as it is efficiently converted and excreted.
Primary Causes of Elevated Levels
The most frequent reason for elevated methylmalonic acid is Vitamin B12 deficiency. Without adequate B12, the enzyme methylmalonyl-CoA mutase cannot function effectively, leading to MMA accumulation in blood and urine. This deficiency can stem from insufficient dietary intake, especially for vegans or vegetarians, as B12 is primarily found in animal products.
Malabsorption issues are another common cause, preventing the body from absorbing enough B12. Conditions like pernicious anemia or gastrointestinal surgeries (e.g., gastric bypass) can impair B12 absorption. Digestive disorders like Crohn’s disease and celiac disease, along with certain medications (e.g., metformin, proton pump inhibitors), may also interfere with B12 absorption or utilization. Symptoms prompting B12 deficiency testing include fatigue, weakness, and neurological issues like numbness, tingling, memory difficulties, and balance problems.
Other Potential Contributors to High MMA
Beyond Vitamin B12 deficiency, other conditions can contribute to elevated methylmalonic acid levels. Kidney dysfunction is a factor, as kidneys are primarily responsible for filtering and excreting MMA. When kidney function is impaired, MMA accumulates in the bloodstream due to reduced clearance, not a metabolic processing issue. As chronic kidney disease progresses, MMA levels increase.
Rare inherited metabolic disorders, known as methylmalonic acidemia, are another cause. These conditions stem from genetic defects that impair the body’s ability to break down certain proteins and fats, often due to issues with the methylmalonyl-CoA mutase enzyme or its Vitamin B12 cofactor processing. These disorders are severe, with symptoms appearing shortly after birth, and can be life-threatening if not diagnosed and managed promptly.
Diagnosing and Managing Elevated MMA
When a high methylmalonic acid level is detected, healthcare providers order further tests to identify the underlying cause. This includes measuring Vitamin B12 and homocysteine levels, another metabolic marker elevated in B12 deficiency. A high MMA level, even with normal B12, can indicate a functional B12 deficiency, meaning the body isn’t effectively utilizing the vitamin. For suspected genetic disorders like methylmalonic acidemia, specialized urine organic acid analysis and genetic testing are performed.
Management strategies depend on the identified cause. For Vitamin B12 deficiency, treatment involves B12 supplementation (oral or injections), depending on severity and cause. If kidney dysfunction is the cause, managing the underlying kidney condition is the primary approach. For inherited methylmalonic acidemia, treatment involves specialized dietary management, often restricting certain proteins, along with specific medications and, for some types, B12 injections. Consulting a healthcare professional is important for accurate diagnosis and a personalized treatment plan.