ORGANIC ACID DISORDER
Disorder name: Methylmalonic Acidemia
- What is MMA?
- What causes MMA?
- If MMA is not treated, what problems occur?
- What is the treatment for MMA?
- What happens when MMA is treated?
- What causes the enzyme to be absent or not working correctly?
- How is MMA inherited?
- Is genetic testing available?
- What other testing is available?
- Can you test during a future pregnancy?
- Can other members of the family have MMA or be carriers?
- Can other family members be tested?
- How many people have MMA?
- Does MMA happen more often in a certain ethnic group?
- Does MMA go by any other names?
- Where can I find more information?
This fact sheet contains general information about MMA. Every child is different and some of these facts may not apply to your child specifically. Certain treatments may be recommended for some children but not others. All children with MMA should be followed by a metabolic doctor in addition to their primary care provider.
WHAT IS MMA?
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.
|This is a group of rare inherited conditions. OA disorders are caused by one or more enzymes that do not work properly. People with these conditions cannot digest certain parts of protein from the food they eat. This causes harmful substances to build up in their blood and urine. This can cause serious effects on health, growth, and learning.:
Organic acid disorders (OAs) are a group of rare Acquiring a trait from one’s parents. Most traits, such as eye color or hair color, are inherited from a parent through genes. conditions. They are caused by enzymes that do not work properly. A number of A molecule that helps chemical reactions take place. For example, enzymes in the stomach speed up the process of breaking down food. Each enzyme can participate in many chemical reactions without changing or being used up. are needed to process protein from the food we eat for use by the body. Problems with one or more of these enzymes can cause an organic acid disorder.
People with organic acid disorders cannot break down A molecule that makes up many parts of every cell in the body. Examples of proteins include hormones, enzymes, hair, and antibodies. Proteins are made up of 20 different types of individual units called amino acids. It is the order of these amino acids in a protein that determines what form and function a protein has. Each gene holds the instructions for making a single protein. properly. This causes harmful substances to build up in their blood and urine. These substances can affect health, growth, and learning.
The symptoms and treatment vary between different organic acid disorders. They can also vary from person to person with the same organic acid disorder. See the fact sheets for each specific organic acid disorder.
Organic acid disorders are inherited in an autosomal recessive manner and affect both males and females.
WHAT CAUSES MMA?
In order for the body to use protein from the food we eat, it is broken down into smaller parts called Amino acids are small molecules that make up proteins. There are over 100 different amino acids, but our body uses only 20 amino acids to make all of its proteins. Our genes determine the sequence of amino acids in a protein. This sequence determines what shape the protein takes, and what function that protein serves in the body.. Special enzymes then make changes to the amino acids so the body can use them. In the same way, Fat is one of the three main nutrients in food (carbohydrates, fat, protein). Some foods that contain fat are butter, margarine, oils, nuts, meats, poultry, fish and some dairy products. Extra calories from food are stored as body fat. Stored body fat provides the body with a reserve supply of energy. 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 These are the building blocks of fat. Fat from food is broken down by enzymes into fatty acids. These are changed by other enzymes and are used as energy or stored as body fat. Some types of fatty acids are: short-chain, medium-chain, long-chain, and very-long chain. cannot be used correctly. This causes This is one of 20 amino acids that make up protein. It has many functions, one of which is helping cells create energy for the body. It is made by the body and does not need to be eaten in the diet. It is also available as a supplement. People with isovaleric acidemia (IVA) are often given glycine to help prevent health problems., This is a substance made when the body digests food containing protein and fat. Normally, it is quickly changed by the body into other substances. If the body is missing an enzyme needed to break down methylmalonic acid, it builds up in the blood and causes illness. Excess methylmalonic acid is found in the blood of people with methylmalonic acidemia., and other harmful substances to build up in the blood and urine and cause health problems.
There are a number of different types of MMA. Some types can be treated with This is a type of B vitamin. It is also called cobalamin. It helps in the breakdown and use of food for energy. It also helps to make red blood cells and keep the nervous system healthy. It is found in meat, dairy products, and eggs. It can also be given by injection to people who have low levels or who have certain metabolic disorders. 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 types 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.
Another type of MMA, called ‘MMA with homocystinuria,’ is described in a separate fact sheet. See the fact sheet MMA+HCU for more information about this condition.
This is one of 20 amino acids that make up protein. It is not made by the body and must be eaten in the diet. It is found in all foods that contain protein., This is one of 20 amino acids that make up protein. It is not made by the body and must be eaten in the diet. It is found in all foods that contain protein., This is one of 20 amino acids that make up protein. It is not made by the body and must be eaten in the diet. It is found in all foods that contain protein., and threonine are the four amino acids that cannot be used correctly by people with MMA. These amino acids are found in all foods that contain protein. Large amounts are found in meat, eggs, milk, and other dairy products. Smaller amounts are found in flour, cereal, and some vegetables and fruits.
IF MMA IS NOT TREATED, WHAT PROBLEMS OCCUR?
Each child with MMA is likely to have somewhat different effects. Many babies with MMA start having symptoms in the first few days of life. Others begin to show symptoms sometime in infancy or childhood. Some people with MMA may never develop symptoms.
MMA causes episodes of illness called metabolic crises. Some of the first symptoms of a This is a serious health condition caused by low blood sugar and the build-up of toxic substances in the blood. Symptoms of a metabolic crisis are poor appetite, nausea, vomiting, diarrhea, extreme sleepiness, irritable mood and behavior changes. If not treated, breathing problems, seizures, coma, and sometimes even death can occur.Metabolic crises happen more often in people with certain metabolic disorders (some fatty acid oxidation disorders, amino acid disorders, and organic acid disorders). They are often triggered by things like illness or infection, going without food for a long time, and, in some cases, heavy exercise. are:
- poor appetite
- extreme sleepiness or lack of energy
- low muscle tone (floppy muscles and joints)
Common blood and urine findings are:
- ketones in the urine
- high levels of acidic substances in the blood, called This happens when acidic substances build up in the blood. It can cause rapid breathing, confusion, and extreme sleepiness. If not treated, it may lead to shock, coma or death.
- high blood ammonia levels
- high blood and urine levels of glycine
- high blood and urine levels of methylmalonic acid and This is one type of fatty acid. Large amounts build up in the blood of people with a metabolic disorder called propionic acidemia. If not treated, this condition can cause serious health problems.
- high levels of other harmful substances
- low This is a type of blood cell that helps to clot the blood. Platelets help prevent or control bleeding.
- low white blood The smallest living unit. Cells make up all organs and tissues in multi-cellular organisms, like humans. They can also live independently, as in bacteria and other microorganisms. At a minimum, a cell is surrounded by a membrane, contains DNA at some stage in its life, and is able to replicate itself into two equal parts.
- This is a condition in which the blood has too few red blood cells or too little hemoglobin, the oxygen carrying molecule in the blood. People with anemia are often pale, tired, weak, dizzy and short of breath.
If a metabolic crisis is not treated, a child with MMA can develop:
- breathing problems
- These are also called "convulsions" or "fits." During a seizure, a person loses consciousness and control of his or her muscles. It may also cause involuntary movements. Seizures can happen for many reasons. Some causes are metabolic disorders, a metabolic crisis, brain injury, and infection.
- This is when the blood or oxygen supply to part of the brain is stopped. It can be caused either by a blood clot or a leak in a blood vessel. A stroke may cause loss of speech and language and the ability to move certain body parts. If severe, it can cause death.
- This is a sleep-like condition from which a person cannot be awakened. People in a coma are unconscious. A coma can be caused by many things. Two causes are untreated low blood sugar (hypoglycemia) and a metabolic crisis., sometimes leading to death
A metabolic crisis can be triggered by:
- eating large amounts of protein
- illness or infection
- going too long without food
- stressful events such as surgery
Between episodes of metabolic crisis, children with MMA may be healthy. However, some continue to have problems with health and development. Some children have long-term problems even if they have never had a metabolic crisis. These can include:
- learning problems or intellectual disabilities
- delays in walking and motor skills
- abnormal involuntary movements (dystonia and chorea)
- rigid In order to hold our posture and control our movements, a certain amount of tension is needed in our muscles. This tension is called “muscle tone.” People with hypotonia have too little tension in their muscles and appear “floppy.” People with hypertonia have too much tension in their muscles and have problems with tight, rigid muscles and joints., called This is rigidity of the muscles and increased reflexes. It is caused by increased muscle tone. It results in abnormal tightness or stiffness of the muscles and joints.
- poor growth with short stature
- skin rashes and infections
- This is a condition that causes the bones to become thinner over time. People with this condition have a higher chance for bone fractures.
- enlarged liver
- kidney disease or failure
- vision loss due to problems with the nerves in the eye
Without treatment, brain and nerve damage can occur. This can cause intellectual disabilities and problems with involuntary movements. Death is common in untreated babies and children.
A small number of people with MMA never have any symptoms.
WHAT IS THE TREATMENT FOR MMA?
Your baby’s primary doctor will work with a This is a doctor or medical geneticist who has special training in diagnosing and treating metabolic disorders. They often work in university hospitals or large medical centers. and a dietician familiar with MMA to care for your child.
Prompt treatment is needed to reduce the chance for intellectual disabilities 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:
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 type 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 a short period of time to determine whether this treatment is useful.
Children with MMA may benefit by taking This is a natural substance found in muscle cells. It helps the body make energy from the fat in food and the fat stored in the body. It also helps the cells get rid of harmful wastes made during the breakdown of fat. Carnitine supplements may be used as a treatment for some metabolic disorders.. 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 This is a small tube placed into a vein, usually in the hand or arm. Medications and nutrients can be given through this tube directly into the blood. IV’s are often used in the hospital to give fluids, glucose and medication over a long period of time. 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 formula and foods
A food plan low in the amino acids This is one of 20 amino acids that make up protein. It is not made by the body and must be eaten in the diet. It is found in all foods that contain protein., valine, methionine, and This is one of 20 amino acids that make up protein. It is not made by the body and must be eaten in the diet. It is found in all foods that contain protein. with limited amounts of protein is often recommended. Most food in the diet will be carbohydrates (bread, cereal, pasta, fruit, vegetables, etc.). This is one of the three types of nutrients in food (carbohydrates, fats, proteins). Sugars and starches are the most important types of carbohydrates. They are broken down by the body into glucose, the main source of energy for the body. Carbohydrates are found in foods such as: bread, cereal, pasta, grains, fruits and vegetables. Milk and dairy products, fruit drinks, sugar, candy, and sweet desserts also contain 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
- 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 This is a person with special training in food and nutrition. A registered dietician (RD) has met the necessary educational requirements and has passed a national examination. If your child has a metabolic disorder, it is important for you to work with a registered dietician. They help create healthy food plans for people with metabolic disorders or other special needs. 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 for this formula and special foods, and others 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
The process of testing a disease for a person who does not appear to have the disease (non-symptomatic or asymptomatic). The goal of tracking is to find the disease in its earliest stages. of These are substances made when the body breaks down fat (fatty acids) for energy. In people with certain metabolic disorders or diabetes, ketones can build up in the blood and spill over into the urine. If ketones build up in the blood, they can cause acidosis which can lead to serious health problems.
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 illnesses, and during periods of heavy exercise. Too many ketones in the urine may signal the start of a metabolic crisis.
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 illnesses 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
- infection or illness
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 illnesses 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.
WHAT HAPPENS WHEN MMA IS TREATED?
Babies and children who have prompt and ongoing treatment may be able to live healthy lives with normal growth and development. In general, the earlier treatment is started, the better the outcome.
Children who respond to vitamin B12 treatment tend to do very well as long as treatment is continued. Children who are not treated until after they have symptoms may have lasting health and learning problems.
Even with treatment, some children develop life-long learning problems or intellectual disabilities. In addition, despite treatment, seizures, involuntary movement disorders, and kidney failure have occurred in some children.
WHAT CAUSES THE ENZYME TO BE ABSENT OR NOT WORKING CORRECTLY?
Genes tell the body how to make enzymes. MMA is caused by changes in one of five sets of A segment of DNA that contains the instructions to make a specific protein (or part of a protein). Genes are contained on chromosomes. Chromosomes, and the genes on those chromosomes, are passed on from parent to child. Errors in the DNA that make up a gene are called variants and can lead to diseases. – MMUT, MMAA, MMAB, MMADHC, and MCEE. Each of these genes provides the instructions for a specific enzyme. Everyone has two copies of each of these five genes. People with MMA have changes (A variant is a change or alteration in a person’s DNA sequence. Variants can happen in genes and affect how the gene functions. There are different types of variants – they can be non-problem causing (benign), disease-causing (pathogenic) or of unknown significance. The term variants is now used in place of the term mutation.) in both copies of one of these five genes. Because of the variants in their genes, one of their enzymes either does not work properly or is not made at all.
HOW IS MMA INHERITED?
MMA is inherited in an autosomal recessive manner. It affects both boys and girls equally.
Everyone has two copies of the genes that make the MMA enzymes. In children with MMA, both copies of these genes do not work correctly. These children inherit one non-working gene for MMA from each parent.
Parents of children with MMA rarely have the disorder. Instead, each parent has a single non-working gene for MMA. They are called A person who has one copy of a gene mutation for a particular autosomal recessive disorder (remember genes come in pairs). Carriers are not affected by the disorder. However, they can pass on the gene variant to their children. Children who inherit two such gene variants will be affected by the disorder. The term variants is now used in place of the term mutation.. Carriers do not have MMA because their other gene is working correctly.
When both parents are carriers, there is a 25% chance in each pregnancy for the child to have MMA. There is a 50% chance for the child to be a carrier, just like the parents. And, there is a 25% chance for the child to have two working genes.
Relating to (or due to) genes and heredity or the field of studying genes and heredity. counseling is available to families who have children with MMA. Genetic counselors can answer your questions about how MMA is inherited, choices during future pregnancies, and how to test other family members. Ask your doctor about a referral to a These are health care providers who have special training in genetic conditions. They help families understand genetic disorders and how they are passed down. Genetic counselors offer information and support to people who have genetic conditions in their families or are concerned that they may have a child with an inherited disorder..
IS GENETIC TESTING AVAILABLE?
Genetic testing is available for MMA. Genetic testing, also called DNA testing, looks for changes (variants) in the pair of genes that cause MMA. Talk with your genetic counselor or metabolic doctor if you have questions about Deoxyribonucleic acid (DNA) is a molecule found in the chromosomes that carries genetic information. DNA is composed of four units (called bases) that are designated A, T, G, and C. The sequence of the bases spell out instructions for making all of the proteins needed by an organism. A gene is a section of DNA that holds the instructions for a specific protein. A change in one or more of the DNA bases making up a gene is called a mutation. Some mutations change the protein instructions and can lead to particular health problems or disorders. Each parent passes half of their chromosomes, and thus half of their DNA instructions, onto their children. It is these instructions that cause certain traits, such as eye or hair color, to be inherited. testing.
DNA testing is not necessary to diagnose your child. However, if available, it can be helpful for carrier testing or prenatal diagnosis, discussed below.
WHAT OTHER TESTING IS AVAILABLE?
Special tests on blood, urine, or skin samples can be done to help confirm MMA. Talk to your metabolic doctor or genetic counselor if you have questions about testing for MMA.
CAN YOU TEST DURING A FUTURE PREGNANCY?
If both gene changes have been found in your child with MMA, DNA testing can be done during future pregnancies. The sample needed for this test is obtained by either CVS or This is a test done during pregnancy. A needle is used to remove a small sample of fluid from the sac around the fetus. The sample can be used to test for certain genetic disorders in the fetus. Amniocentesis to test for genetic conditions is usually done between 13 and 20 weeks of pregnancy..
If DNA testing would not be helpful, MMA can also be detected by an enzyme test using cells from the fetus. The sample needed for this test is obtained by amniocentesis.
Parents may either choose to have testing during pregnancy or wait until birth to have the baby tested. Parents may also choose to use assisted reproductive techniques to decrease the chance that their future children would have MMA. A genetic counselor can talk to you about your choices and answer questions about prenatal testing or testing your baby after birth.
CAN OTHER MEMBERS OF THE FAMILY HAVE MMA OR BE CARRIERS?
If they are healthy and growing normally, older brothers and sisters of a baby with MMA are unlikely to have the condition. However, finding out if other children in the family have this condition is important because early treatment can prevent serious health problems. Ask your metabolic doctor whether your other children should be tested to see if they also have MMA.
Brothers and sisters who do not have MMA still have a chance to be carriers like their parents. Except in special cases, carrier testing should only be done on people over 18 years of age.
If you are a parent of a child with MMA, your brothers and sisters have a 50% chance to be an MMA carrier. It is important for other family members to be told that they could be carriers. There is a small chance they are also at risk to have children with MMA.
All states provide newborn screening for MMA. However, when both parents are MMA carriers, A screening test that looks for different disorders using a small sample of blood taken from a newborn’s heel. A positive or abnormal newborn screening result means that there are slight differences that were found in the baby’s blood, and further testing is needed to figure out if the baby has a metabolic disorder. results are not sufficient to rule out the condition in a newborn baby. In this case, special diagnostic testing should be done in addition to newborn The process of testing for disease in a person who does not show signs of having the disease (nonsymptomatic or asymptomatic person). The goal of screening is to catch the disease in its early stages..
CAN OTHER FAMILY MEMBERS BE TESTED?
Brothers and sisters of a child with MMA can have special tests on blood, urine, or skin samples to see if they also have MMA. Talk to your doctor or genetic counselor if you have questions about testing for MMA.
If the gene changes have been identified in your child with MMA, carrier testing can be done for other family members. If you have questions about carrier testing, ask your genetic counselor or metabolic doctor.
HOW MANY PEOPLE HAVE MMA?
About one in 80,000 babies in the United States is born with MMA.
DOES MMA HAPPEN MORE OFTEN IN A CERTAIN ETHNIC GROUP?
MMA occurs in all ethnic groups around the world. It does not occur more often in any specific race, ethnic group, geographical area, or country.
DOES MMA GO BY ANY OTHER NAMES?
There are a number of different types of MMA. The vitamin B12 non-responsive types are sometimes also called:
- Methylmalonic aciduria due to methylmalonic CoA mutase deficiency
- Complementation group Mut (includes Mut0 and Mut-)
- Methylmalonyl CoA mutase deficiency
- MCM Deficiency
The vitamin B12 responsive types are sometimes also called:
- Methylmalonic aciduria, cblA type
- Methylmalonic aciduria, cblB type
- Adenosylcobalamin deficiency
Another type of MMA has additional symptoms of a separate condition called homocystinuria. See the fact sheet MMA+HCU for more information about this type of MMA.
WHERE CAN I FIND MORE INFORMATION?
Organic Acidemia Association
Metabolic Support UK
Genetics Home Reference
Save Babies Through Screening Foundation
Baby’s First Test
|Reviewed by:||HI, CA, OR, and WA metabolic specialists|
|Review date:||May 28, 2020
July 7, 2016
May 1, 2011
September 31, 2007
|Update on:||May 28, 2020|
THIS INFORMATION DOES NOT PROVIDE MEDICAL ADVICE. All content (“Content”), including text, graphics, images and information are for general informational purposes only. You are encouraged to confer with your doctor or other health care professional with regard to information contained on this information sheet. After reading this information sheet, you are encouraged to review the information carefully with your doctor or other healthcare provider. The Content is not intended to be a substitute for professional medical advice, diagnosis or treatment. NEVER DISREGARD PROFESSIONAL MEDICAL ADVICE, OR DELAY IN SEEKING IT, BECAUSE OF SOMETHING YOU HAVE READ ON THIS INFORMATION SHEET. This project is supported by a grant from the Having to do with the mother. and Child Health Bureau, Health Resources and Service Administration, Genetic Services Branch, MCH Project #:UH7MC30774-01-00 http://mchb.hrsa.gov