Methylmalonic Acid, GC/MS/MS, Urine (MMA)

The Methylmalonic Acid, GC/MS/MS, Urine (MMA) test contains 1 test with 2 biomarkers.

Brief Description: The Methylmalonic Acid (MMA) urine test measures the amount of MMA present in the urine. Methylmalonic acid is a substance in the body that is produced when certain proteins are broken down. Under normal circumstances, MMA is then converted into another substance by the action of vitamin B12. If there's a deficiency of vitamin B12, the level of MMA in the body can rise, leading to its increased excretion in the urine.

Collection Method: Urine Collection

Specimen Type: Urine

Test Preparation: No preparation required

When is a Methylmalonic Acid test ordered?

When a vitamin B12 test result comes back low, an MMA test may be performed, sometimes coupled with a homocysteine test.

Asymptomatic persons with a higher risk of vitamin B12 insufficiency, such as the elderly, or those using certain medicines for a long period, such as Metformin, are also given MMA. If the two tests are not scheduled together, an MMA test may be ordered as a follow-up to an increased homocysteine level.

When a doctor fears that an acutely unwell child has inherited methylmalonic acidemia, MMA testing may be recommended.

What does a Methylmalonic Acid Urine test check for?

Methylmalonic acid is a naturally occurring chemical that is required for human metabolism and energy generation. Vitamin B12 aids in the conversion of methylmalonyl CoA to succinyl Coenzyme A in one step of metabolism. If there isn't enough B12, the MMA concentration rises, resulting in an increase in MMA levels in the blood and urine. Methylmalonic acid levels that are high in the blood or urine are a sensitive and early sign of vitamin B12 insufficiency.

Anemia and the formation of big red blood cells can occur as a result of vitamin B12 deficiency over time. It can also induce neuropathy symptoms including numbness and tingling in the hands and feet, as well as mental or behavioral problems like cognitive impairment, disorientation, irritability, and depression in severe cases. Though some patients may have some degree of neuropathy, an increased concentration of MMA may frequently be detected before blood cell alterations and full-blown symptoms appear.

Although the link between MMA and B12 has been recognized for over 40 years, MMA testing is not widely used, and there is no consensus on its clinical relevance. Some doctors believe that MMA is a better indicator of bioavailable B12 than the standard vitamin B12 test since a considerable portion of B12 detected in the blood is bound to proteins and is not biologically active. Others feel that measuring MMA and homocysteine can help detect early and mild B12 insufficiency. Others believe that many moderate deficits diagnosed do not evolve to more serious deficiencies and so do not require identification or treatment.

Methylmalonic acidemia is a rare metabolic condition that affects roughly 1 in 25,000 to 100,000 people. Testing babies for high levels of MMA could help doctors diagnose it. Screening for this disease is required in all 50 states in the United States. This condition prevents babies from converting methylmalonyl CoA to succinyl CoA. They appear normal at birth, but as they consume protein, symptoms such excessive exhaustion, vomiting, dehydration, weak muscle tone, seizures, mental retardation, strokes, and severe metabolic acidosis emerge.

This test also checks creatinine urine levels.

Creatinine is a waste product created by muscles when a molecule called creatine is broken down. The kidneys eliminate creatinine from the body by filtering almost all of it from the blood and excreting it in the urine. The level of creatinine in the urine is measured in this test.

Creatine is a component of the energy-producing cycle that allows muscles to contract. The body produces both creatine and creatinine at a roughly steady rate. Because the kidneys filter almost all creatinine from the blood and excrete it in the urine, blood levels are usually an excellent predictor of how well the kidneys are operating. The amount produced is determined by the person's size and muscular mass. As a result, men's creatinine levels will be slightly higher than women's and children's.

Lab tests often ordered with a Methylmalonic Acid test:

When a Urine Methylmalonic Acid test is ordered, it's often part of a broader evaluation of B12 deficiency and its potential causes. Here are some tests commonly ordered alongside it:

1. Serum Vitamin B12 Test:

   • Purpose: To measure the level of vitamin B12 in the blood.
   • Why Is It Ordered: To directly assess vitamin B12 status. Low levels can confirm a deficiency, which can be correlated with elevated MMA levels.

2. Complete Blood Count (CBC) with Differential:

   • Purpose: To evaluate overall blood health.
   • Why Is It Ordered: To check for macrocytic anemia, a condition where red blood cells are larger than normal, often associated with B12 deficiency.

3. Serum Homocysteine:

   • Purpose: To measure the level of homocysteine in the blood.
   • Why Is It Ordered: Elevated homocysteine levels can also indicate B12 deficiency, as well as folate deficiency.

4. Folate (Folic Acid) Test:

   • Purpose: To measure the level of folate in the blood.
   • Why Is It Ordered: To differentiate between vitamin B12 deficiency and folate deficiency, which can present with similar hematological findings.

5. Intrinsic Factor Antibody and Parietal Cell Antibody Tests:

   • Purpose: To detect antibodies that can inhibit vitamin B12 absorption.
   • Why Is It Ordered: To evaluate for pernicious anemia, an autoimmune condition that impairs vitamin B12 absorption and is a common cause of B12 deficiency.

6. Reticulocyte Count:

   • Purpose: To count young red blood cells (reticulocytes).
   • Why Is It Ordered: To assess bone marrow response, especially following B12 supplementation in B12 deficiency anemia.

7. Liver Function Test:

   • Purpose: To assess liver health.
   • Why Is It Ordered: To rule out liver disease as a cause of elevated MMA, and because liver disorders can also affect B12 metabolism.

8. Kidney Function Test:

   • Purpose: To assess kidney function.
   • Why Is It Ordered: To ensure that kidney dysfunction is not contributing to elevated MMA levels, as renal impairment can lead to increased MMA.

These tests, when ordered alongside a Urine MMA test, provide a comprehensive evaluation of vitamin B12 status and help identify the underlying cause of a deficiency. They are crucial for diagnosing B12 deficiency, differentiating it from other similar conditions, and guiding appropriate treatment. The specific combination of tests will depend on the individual’s symptoms, clinical presentation, and medical history.

Conditions where a Methylmalonic Acid test is recommended:

The primary condition associated with elevated MMA levels in the urine is Vitamin B12 Deficiency. However, the root cause of the deficiency can vary:

• Pernicious Anemia: An autoimmune condition where the stomach lacks intrinsic factor, a protein required for B12 absorption.
• Dietary Deficiency: Especially in individuals following a strict vegan diet.
• Malabsorption: Conditions like celiac disease, atrophic gastritis, or Crohn's disease can impact B12 absorption.
• Certain Medications: Such as proton pump inhibitors or metformin, which can reduce B12 absorption.
• Overconsumption of Alcohol: Can interfere with B12 absorption and metabolism.

How does my healthcare provider use a Methylmalonic Acid test?

The methylmalonic acid test can be used to determine a vitamin B12 deficiency that is mild or early. It can be ordered alone or in conjunction with a homocysteine test as a follow-up to a vitamin B12 test result that falls below the normal range.

MMA is a chemical produced in the body in extremely minute amounts. It is required for metabolism and the creation of energy. Vitamin B12 aids in the conversion of methylmalonyl CoA to succinyl Coenzyme A in one step of metabolism. If there isn't enough B12, the MMA level rises, resulting in an increase in MMA levels in the blood and urine. Methylmalonic acid levels in the blood or urine can be used to detect vitamin B12 insufficiency early.

There are currently no standards for screening asymptomatic adults for vitamin B12 deficiency, however those at high risk without symptoms, such as the elderly or those taking particular drugs for a long time, may require confirmation with MMA and/or homocysteine.

The MMA test is quite sensitive in detecting a B12 deficiency. It is the preferred confirmatory test for a B12 deficiency because it is more specific than homocysteine.

MMA testing may be conducted in some cases to assist detect methylmalonic acidemia, a rare inherited metabolic condition. In all 50 states in the United States, newborn screening programs currently require testing for this disease.

What do my Methylmalonic Acid test results mean?

Early stages of B12 deficiency may be evident if MMA and homocysteine levels are elevated while vitamin B12 levels are mildly diminished. This could indicate a decrease in B12 availability in the tissues.

If only the homocysteine level is high but not the MMA, the person may be deficient in folate. This distinction is critical because treating anemia with folate treats the anemia but not the brain damage, which may be irreparable.

If both MMA and homocysteine levels are within normal limits, a B12 shortage is unlikely.

Infants with the rare hereditary illness methylmalonic acidemia may have moderately to severely high levels of MMA.

Reduced MMA levels are uncommon and are not considered clinically significant.

Most Common Questions About the Methylmalonic Acid Urine test:

Purpose and Indications for the Methylmalonic Acid (MMA) Urine Test

Why is the Methylmalonic Acid (MMA) Urine test ordered?

The Methylmalonic Acid Urine test is primarily ordered to assist in the diagnosis of vitamin B12 deficiency. Elevated levels of MMA can be indicative of a B12 deficiency, as B12 is needed to break down MMA. When there's a lack of B12, MMA accumulates in the blood and urine.

What are the primary indications for conducting a Methylmalonic Acid Urine test?

The test is often indicated for individuals showing symptoms of a B12 deficiency, such as fatigue, weakness, constipation, loss of appetite, weight loss, poor memory, or numbness and tingling in the hands and feet.

Interpreting the Results

What do elevated levels of MMA in the urine indicate?

Elevated levels of MMA in the urine usually suggest a deficiency in vitamin B12. It's worth noting that elevated MMA is a more sensitive marker for B12 deficiency than measuring B12 directly, especially in early or mild deficiencies.

Are there any other reasons for elevated MMA levels?

Yes, besides vitamin B12 deficiency, other conditions like kidney disease, intestinal bacterial overgrowth, and inherited metabolic disorders can lead to elevated MMA levels.

Follow-up and Treatment

How can the results from the Methylmalonic Acid (MMA) Urine test influence treatment decisions?

If the Methylmalonic Acid Urine test reveals elevated MMA levels suggestive of B12 deficiency, treatment may include B12 injections or high-dose oral B12 supplements. Following up with repeat testing can help assess if the treatment is effective in restoring B12 levels and reducing MMA.

Disease Monitoring and Complications

Why might a physician monitor MMA levels in a patient with known B12 deficiency?

Monitoring MMA levels in a patient with B12 deficiency helps determine the effectiveness of the treatment. Decreasing MMA levels post-treatment would indicate that B12 levels are being restored and metabolic processes are returning to normal.

Additional Information

Does the Methylmalonic Acid (MMA) Urine test replace other tests for diagnosing vitamin B12 deficiency?

While the MMA Urine test is a sensitive marker for B12 deficiency, it doesn't necessarily replace other diagnostic tools. A complete blood count (CBC) might show changes consistent with B12 deficiency, and measuring serum B12 levels directly is still commonly done. The combination of tests provides a more comprehensive view of the patient's status.

Can diet or hydration status affect the Methylmalonic Acid (MMA) Urine test results?

Yes, severe dehydration can concentrate urine and might lead to falsely elevated MMA levels. Additionally, consuming large amounts of certain foods like bacterial fermented foods might transiently increase MMA levels. It's essential for patients to inform their physicians about their dietary habits and hydration status.

We advise having your results reviewed by a licensed medical healthcare professional for proper interpretation of your results.