What Is MMA?
When the body cannot metabolize protein, severe metabolic disturbances like those seen in Methylmalonic acidemia (MMA) can result. MMA is a group of inherited genetic disorders that result in the build up of methylmalonic acid in the bloodstream. This build up can lead to severe metabolic ketoacidosis, which can be fatal for the affected patient. The main cause of this disorder is a defect in the conversion of methylmalonyl CoA to succinyl CoA, caused by mutations in the methylmalonyl CoA mutase enzyme or impaired metabolism of vitamin B12. This disorder affects about 1 in 25,000 to 48,000 people. This rate may be higher because some neonatal deaths may be attributed to undiagnosed metabolic disorders.
Methylmalonic acidemia (pronounced meth-il-ma-lon-ic a-cid-em-ia) or MMA is a disorder of amino acid and odd-chain fatty acid metabolism. (Odd chain fatty acids are ones with an uneven number of carbons and produce some propionyl CoA , a precursor of MMA when they are used in the body. They are found in butter, chicken fat, cream, some fish oils, lard, and olive oil.)
Proteins, which are made up of amino acids, are found in all parts of the human body such as blood, skin and muscles. Most foods contain protein. When we eat foods containing protein, this protein is split into amino acids during digestion. The amino acids are later put back together like beads on a necklace to form new protein. These new proteins are used to build and repair the body's tissues. (1)
Twenty amino acids occur commonly in the human body and in the foods we eat. Four of these amino acids are isoleucine (i-so-lu-seen), methionine (me-thi-o-neen), threonine (three-o-neen) and valine (vay-leen). Children with MMA can't use these amino acids and some fats in a normal way. (2)
Splitting protein into amino acids requires a special substance. Think of the splitting substance as a pair of scissors snipping beads off of a necklace. These “scissors” are called enzymes. Once the four amino acids are split off of food protein and absorbed, they're used to help form many other useful substances in the body. (3)
For the body to use excess amounts of these amino acids and some fats instead as energy, another enzyme called methylmalonyl CoA mutase (mu-tace), or MCM is needed. In addition, vitamin B12 must be present in adequate amounts and in the proper form called adenosylcobalamin, for methylmalonyl CoA mutase to work. Some people, for example those with MMA, do not have working MCM, or the proper form of vitamin B12, to handle all the ILE, MET, THR, VAL, and some types of fat that are in the foods they eat. In either case, ILE, MET, THR, VAL and some other fats can't be used normally. They build up in the body as methylmalonic acid and other toxic (poisonous) substances such as propionic acid (pro-pee-on-ic a-cid) and spill into the urine. This excess keeps another important substance, coenzyme A (CoA), from working, and causes the symptoms of MMA. (4)
Think of the situation as a traffic intersection. A green traffic light (normal MCM) allows ILE, MET, THR, VAL, and the odd-chain fatty acids to be used normally. A red light (no or too little MCM) keeps ILE, MET, THR, VAL, and some fats from being used. If the light is stuck on red, a traffic jam occurs, and the toxic products listed above increase. (5)
1,2,3,4 and 5: Taken from “ A Guide for the Family of the Child With Methylmalonic Acidemia” , The Ross Metabolic Formula System, Mitzi A. Bame, Abbot Laboratories, 2001. Booklet 33 pages.)