Methylmalonic Acid Test

Methylmalonic Acid Test

Overview

A methylmalonic (meth-uhl-muh-LAHN-ick) acid test is a way to test for vitamin B12 deficiency. Your provider uses a sample of your blood or urine (pee) to look for high levels of methylmalonic acid (MMA). When you have low levels of B12 (also called cobalamin) or you aren’t absorbing B12 properly, your body makes more MMA.

Why would I need an MMA test?

Your provider might order a methylmalonic acid blood test:

If you have symptoms of B12 deficiency, like feeling tired or weak, digestive issues (like diarrhea or abdominal pain), numbness or tingling in your hands or feet, or lack of appetite.

At birth, to screen for methylmalonic acidemia (also called methylmalonic aciduria), a rare genetic disorder.

Providers most often use an MMA urine test to monitor methylmalonic acidemia.

It’s important to accurately diagnose B12 deficiency because it can be a sign of health conditions that can lead to nerve damage, like pernicious anemia and diabetes-related neuropathy.

Types of Methylmalonic Acid Tests

Blood Test (Serum MMA Test): A blood sample is taken to measure the level of MMA in the bloodstream. This is the most commonly used method for detecting vitamin B12 deficiency.

Urine Test (Urinary MMA Test): A urine sample is used to measure the amount of MMA being excreted. This test can be useful in confirming a vitamin B12 deficiency but is less commonly performed than the blood test.

Both tests provide valuable information about the body’s ability to convert methylmalonic acid into other substances and help diagnose B12 deficiency

Symptoms

1.Neurological Symptoms:

Numbness and tingling: These sensations can occur in the hands and feet. 

Cognitive difficulties: Impairment in memory and other cognitive functions can be present. 

Fatigue and weakness: Feeling tired and weak is a common complaint. 

Seizures: In severe cases, seizures can occur. 

Developmental delays: In children, delays in reaching developmental milestones can be a sign. 

2.Hematological Symptoms:

Anemia: A low red blood cell count can result from a B12 deficiency, which can cause MMA levels to be elevated. 

3.Other Symptoms:

Diarrhea: Digestive problems are a frequent symptom.

Loss of appetite: A reduced desire to eat can be a sign.

Mood changes: Changes in mood and behavior can occur.

Confusion: Mental clarity can be affected.

Irritability: Increased irritability is also a possible symptom.

Pale skin: A pale complexion can be associated with anemia.

Failure to thrive: Infants and children may not grow and develop as expected.

Vomiting: This can be a sign of metabolic decompensation.

Lethargy: Excessive tiredness and lack of energy.

Dehydration: In severe cases, dehydration can occur. 

Methylmalonic Acidemia (MMA):

Elevated MMA levels can be a sign of methylmalonic acidemia, a genetic disorder where the body cannot properly break down certain amino acids and fats.

This condition can lead to a range of symptoms, including developmental delays, failure to thrive, and neurological problems. 

Causes

Methylmalonic acidemia belongs in a group of disorders known as inborn errors of metabolism.9

Metabolism refers to how the body converts nutrients in food into energy. Inborn errors of metabolism are caused by different genetic defects that lead to problems with metabolism.

Methylmalonic acidemia also belongs to a smaller subset of these diseases, termed organic acidurias.10 These genetic diseases result from difficulties metabolizing certain types of amino acids, the building blocks of proteins. It results in unhealthy levels of products otherwise normally present in the body.

Defects in different enzymes lead to different types of organic aciduria. For example, propionic acidemia is another rare disease in this class.11 Other rare diseases in this group may have some similar symptoms.

Gene Defects in MMA

More specifically, methylmalonic acidemia can be caused by a defect in one of several different genes. Due to the defect in the gene, the resulting proteins don’t work as well as they should. These defects cause problems with the functioning of a specific protein enzyme, called methylmalonyl-CoA mutase.

In more than 60% of cases, the cause is:10

Mutations in the MMUT gene (methylmalonyl-CoA mutase) responsible for this missing or defective enzyme

Mutations in the MMAA gene (metabolism of cobalamin associated A) responsible for problems with adenosyl-cobalamin, a cofactor related to methylmalonyl-CoA mutase 

Because the function of a key enzyme is impaired with methylmalonic acidemia, the specific amino acid and related compounds found in fats and cholesterol build up to toxic levels and cause symptoms of the disorder, including interference with producing energy for the body.

Diagnosis

The standard newborn screening tests sometimes provide the diagnosis of methylmalonic acidemia.6 However, not all places test for this specific disease. Also, infants might first experience symptoms before the results of these screening tests are available.

Diagnosis of methylmalonic acidemia requires a thorough medical history and exam. Laboratory testing is critical as well. It’s important that diagnosis happens as quickly as possible since affected individuals are often very ill. Also, untreated decompensations can worsen the long-term complications of MMA (for example, causing permanent brain damage).

Many different types of medical problems can lead to neurological and other symptoms such as those seen in decompensated methylmalonic acidemia. It can be a challenge to rule out these other possible diagnoses and narrow down on the specific cause. Since MMA is a rare condition, a medical specialist may be needed to help diagnose the disease.3

One key diagnostic test for MMA looks at how much methylmalonic acid is present in the blood or urine.

In people with MMA, these levels should be higher than usual. However, there are also some other different inborn errors of metabolism that can cause methylmalonic acid to build up as a result of different genetic problems.14

Blood tests that may be helpful in diagnosing methylmalonic acidemia include:

Comprehensive metabolic panel CMP, to check for response to infection, anemia, glucose levels, basic organ function, and more15

Tests for various metabolites such as ammonia

Testing to assess the presence of amino acids16

Samples to assess for bacterial infection

Tests for vitamin B12 and homocysteine

Additional genetic tests can help finalize the diagnosis and can also identify the specific genetic mutation involved. In some cases, this may affect treatment options.

Treatment

Treatment focuses on managing the symptoms. People with MMA must follow a special low-protein diet. Certain medications and antibiotics can be a part of the treatment plan, and people with a particular variation of the disease benefit from vitamin B12 supplements.

For children with MMA, Children’s Hospital of Philadelphia offers a multidisciplinary team that works together to care for patients. Team members might include a dietitian, geneticist, neurologist, ophthalmologist, nephrologist, and physical and occupational therapists.

In some cases, liver transplantation can help children with methylmalonic acidemia lead a more normal life. The healthy transplanted liver expresses the normal enzymes necessary to process dietary proteins. In some cases, patients with MMA may also require kidney transplant.

Type of Doctor Department :  A geneticist or a doctor specializing in metabolic disorders