MMA Disease: Brief Overview of Methylmalonic Acidemia

Let’s start simply.

In order for our body to benefit from the proteins we eat, it has to be broken down into smaller parts called amino acids. There are special enzymes that edit or make changes to those amino acids so that the body can benefit from or use them. Along the same lines, fat from the food we ingest has to be broken down by enzymes into substances called fatty acids that the body uses for energy. MMA is a condition in which the aforementioned processes are disturbed because a particular enzyme is not working properlyas a result of mutations (see below). This prevents the correct use of certain amino acids and fatty acids which causes a build-up of toxic substances in the body—this leads to health problems.

Scientifically speaking, MMA stands for Methylmalonic Acidemia, and in many ways, it can be considered a kind of umbrella term for the many different forms that it represents. MMA is caused by several things, including cobalamin (or vitamin B12) disorders as well as MUT deficiencies. For example, those who are affected by MMA caused by cobalamin A deficiencies have trouble making cobalamin enzyme A. All cobalamin enzymes are important so that the body can break down certain foods (more details below). Furthermore, some forms of MMA can be treated with vitamin B12 injections. They are termed ‘vitamin B12 responsive’ and they are cobalamin A and cobalamin B deficiencies. On the other hand, vitamin B12 non-responsive types cannot be treated with vitamin B12 deficiencies.

Overall, MMA is aninherited condition that is also considered an organic acid condition as it can culminate in a toxic amount of organic acids in the body. It is marked by the body’s lack of ability to break down certain fats and proteins. An estimated one out of every 50,000 to 100,000 babies born in the United States is affected MMA. Early signs of the disease include sleeping longer or more frequently, fever, trouble breathing, vomiting, weak muscle tone, increased bleeding and bruising as well as an increased number of illnesses and infections.


While mutations in several genes can cause MMA (MUT, MMAA, MMAB, MMADHC and MCEE), an estimated 60 percent are caused by mutations in the MUT gene. Furthermore, long-term effects of the disease are largely dependent on which gene is mutated as well as to what extent. The MUT gene is responsible for directing the production of an enzyme with an extremely complicated name, methylmalonyl CoA mutase. It collaborates with vitamin B12 in order to break down several amino acids, certain lipids as well as cholesterol. Essentially, mutations in the MUT gene change the structure of the enzyme that it is responsible for. These mutations also lower the amount of enzyme that is produced, and all that hinders these molecules from being broken down properly. All of this then causes accumulation of the substance methylmalonyl CoA as well as other possibly toxic compounds in organs and tissues. Ultimately, this results in symptoms of MMA.

Furthermore, the MMA cases that are caused by mutations in all the aforementioned genes are caused via the same mechanisms, namely impairment of methylmalonyl CoA mutase. That’s a mouthful, I know. Suffice it to say that there are several genes that affect the production of methylmalonyl CoA mutase, which causes difficulties in the breaking down of fats and lipids, which is a problem.

Genetically speaking, MMA is an autosomal recessive disorder. This means that it is present on an autosome, or on a non-sex chromosome (remember that humans have 23 pairs, 22 autosomes, and either an X or a Y chromosome). Recessive means that a baby must have inherited two copies of the mutation in order to have MMA. Most often, parents of a child with MMA each have one copy of the mutation without actually having any symptoms.

Genetic Testing

Given that MMA is a genetic disease

Given that MMA is a genetic disease, genetic or DNA testing is available for patients to test for the mutations that are known to cause the disease. Genetic testing essentially looks for changes in the genes that cause MMA. While not completely necessary for a diagnosis, it can be helpful during prenatal testing. For example, if both parents find out they are carriers of the mutation, it is advised they speak with a physician or genetic counselor to discuss their options.


Patients, especially babies, who have MMA are typically treated by a doctor as well as a dietician. As with many conditions, the earlier they are detected, the better the chances are in terms of life expectancy as well as success. Children that have vitamin B12 responsive MMA are put on a vitamin B12 regimen together with a low-protein diet as well as a special medical formula. Furthermore, going a long time without food should be avoided so that a metabolic crisis is averted. Eating schedules are created together with a doctor.

Also, regular urine tests are advised so that ketone levels can be tracked. When body fat is broken down for energy, ketones are formed, which is why tracking their levels is a good way of monitoring fat breakdown. Regular blood tests are done so that amino acid concentrations are kept track of. Furthermore, being proactive about monitoring other illnesses in children with MMA can be considered a kind of treatment as that prevents worsening of the condition. Ultimately, some MMA kids may need organ transplants. In particular, liver or kidney transplants are done most frequently because that reduces some of the symptoms. However, organ transplants, particularly in kids, come with their own risks so doctors should be consulted if this is the only option.

Overall, MMA can be considered a rare disease, given its frequency. However, it can be debilitating if not treated properly, which is why remaining informed is important and could save as well as improve lives.

Laura Day