Methylmalonic aciduria cblA type
Overview
MMA stands for “methylmalonic acidemia”. It is one type of organic acid disorder. People with MMA have problems breaking down and using certain amino acids and fatty acids from the food they eat.
Causes
In order for the body to use protein from the food we eat, it is broken down into smaller parts called amino acids. Special enzymes then make changes to the amino acids so the body can use them. In the same way, fat from the food we eat is broken down by enzymes into fatty acids that the body can use for energy. MMA occurs when one of these special enzymes is either missing or not working properly. Without this enzyme, certain amino acids and fatty acids cannot be used correctly. This causes glycine, methylmalonic acid, and other harmful substances to build up in the blood and urine and cause health problems. There are a number of different forms of MMA. Some forms can be treated with vitamin B12 injections. These types are called ‘vitamin B12 responsive’. Two types of MMA that often can be treated with vitamin B12 are Cobalamin A (CblA) deficiency and Cobalamin B (CblB) deficiency. There are other forms of MMA which cannot be treated with vitamin B12. These types are called ‘vitamin B12 non-responsive’. One of these is called ‘Mut 0’. It is caused by the absence of an enzyme called methylmalonyl-CoA mutase (MCM). Another type of MMA that does not respond to vitamin B12 treatment is called ‘Mut –‘. People with the ‘Mut–‘ type of MMA have too little of the MCM enzyme.
Treatment
Your baby’s primary doctor will work with a metabolic doctor and a dietician familiar with MMA to care for your child. Prompt treatment is needed to reduce the chance for mental retardation and serious medical problems. Children with ‘vitamin B12 responsive’ MMA are given vitamin B12. In addition, most children need to be on a low-protein diet and drink a special medical formula. You should start the treatments as soon as you know your child has MMA. The following are treatments often recommended for children with MMA: 1. Medication The main treatment for ‘vitamin B12 responsive’ MMA is vitamin B12 injections in the form of hydroxocobalamin (OH-cbl) or cyanocobalamin (CN-cbl). Vitamin B12 injections can prevent symptoms in children with this form of MMA. Over 90% of children with CblA deficiency respond to vitamin B12 injections. About 40% of children with CblB deficiency are helped by this treatment. Your doctors may need to treat your child with vitamin B12 for short period of time to determine whether this treatment is useful. Children with MMA may benefit by taking L-carnitine. This is a safe and natural substance that helps the body make energy. It also helps get rid of harmful wastes. Your doctor will decide whether or not your child needs L-carnitine. Unless you are advised otherwise, use only L-carnitine prescribed by your doctor. Antibiotics taken by mouth can help lower the amount of methylmalonic acid made in the intestines. Your doctor will decide if your child needs antibiotics and, if so, what type. Children who are having symptoms of a metabolic crisis should be treated in the hospital. During a metabolic crisis, your child may be given medications such as bicarbonate through an IV to help reduce the acid levels in the blood. Glucose is given by IV to prevent the breakdown of protein and fat stored in the body. Do not use any medication without checking with your doctor. 2. Low-protein diet, medical foods and medical formula Low-protein diet A food plan low in the amino acids leucine, valine, methionine, and threonine with limited amounts of protein is often recommended. Most food in the diet will be carbohydrates (bread, cereal, pasta, fruit, vegetables, etc.). Carbohydrates give the body many types of sugar that can be used as energy. Eating a diet high in carbohydrates and low in protein and fat can help prevent metabolic crises. Foods high in protein that may need to be avoided or limited include: milk and dairy products meat and poultry fish eggs dried beans and legumes nuts and peanut butter Many vegetables and fruits have only small amounts of protein and can be eaten in carefully measured amounts. Do not remove all protein from the diet. Children with MMA need a certain amount to grow properly. Your dietician can create a food plan that contains the right amount of protein, nutrients, and energy to keep your child healthy. It is likely your child will need to be on a special food plan throughout life. Medical formula and foods In addition to a low-protein diet, your child may be given a special medical formula. This formula contains the correct amount of protein and nutrients your child needs for normal growth and development. Your metabolic doctor and dietician will tell you what type of formula is best and how much to use. There are also medical foods such as special low-protein flours, pastas, and rice that are made especially for people with organic acid disorders. Your dietician will tell you how to use these foods as part of your child’s diet. Some states offer help with payment or require private insurance to pay for the formula and other special medical foods. 3. Avoid going a long time without food Infants and young children with MMA need to eat frequently to prevent a metabolic crisis. Your metabolic doctor will tell you how often your child needs to be fed. In general, it is often suggested that infants be fed every four to six hours. Some babies need to eat even more frequently than this. It is important that infants be fed during the night. They may need to be woken up to eat if they do not wake up on their own. Your metabolic doctor and dietician will give you an appropriate feeding plan for your infant. Your doctor will also give you a ‘sick day’ plan, tailored to your child’s needs, for you to follow during illnesses or other times when your child will not eat. Your metabolic doctor will continue to advise you on how often your child should eat as he or she gets older. 4. Regular blood and urine tests Tracking of ketones Periodic urine tests to check the level of ketones can be done at home or at the doctor’s office. Ketones are substances formed when body fat is broken down for energy. This happens after going without food for long periods of time, during illness, and during periods of heavy exercise. Too many ketones in the urine may signal the start of a metabolic crisis. Blood tests Your child will have regular blood tests to measure the level of amino acids. Urine tests may also be done. Your child’s diet and medication may need to be adjusted based on the results of these tests. 5. Call your doctor at the start of any illness For children with MMA, even minor illness could lead to a metabolic crisis. To prevent serious health problems, call your doctor right away when your child has any of the following: loss of appetite vomiting diarrhea infection or illness fever When ill, your child needs extra fluids and carbohydrates in order to prevent a metabolic crisis. During an illness, you should restrict protein and give your child starchy foods and fluids. Children with MMA may need to be treated in the hospital during illness to avoid serious health problems. Ask your metabolic doctor if you should carry a special travel letter with medical instructions for your child’s care. 6. Organ transplantation Some children with MMA are given liver or kidney transplants, or both. This may reduce some of the symptoms. However, transplant surgery has serious risks and may or may not be right for your child. Talk with your doctor or metabolic specialist if you have questions about the risks and benefits of transplantation.