ORGANIC ACID DISORDER

Disorder name: 2-methylbutyryl CoA dehydrogenase deficiency
Acronym: 2MBCD deficiency
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• What is 2MBCD deficiency?
• What causes 2MBCD deficiency?
• If 2MBCD deficiency is not treated, what problems occur?
• What is the treatment for 2MBCD deficiency?
• What happens when 2MBCD deficiency is treated?
• What causes the 2MBCD enzyme to be absent or not working correctly?
• How is 2MBCD deficiency inherited?
• Is genetic testing available?
• What other testing is available?
• Can you test during a future pregnancy?
• Can other members of the family have 2MBCD deficiency or be carriers?
• Can other family members be tested?
• How many people have 2MBCD deficiency?
• Does 2MBCD deficiency happen more often in a certain ethnic group?
• Does 2MBCD deficiency go by any other names?
• Where can I find more information?

 

This fact sheet has general information about 2MBCD deficiency. 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. Children with symptoms of 2MBCD deficiency should be followed by a metabolic doctorThis 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. in addition to their primary doctor.

WHAT IS 2MBCD DEFICIENCY?

2MBCD deficiency is one type of organic acid disorder. Some children with 2MBCD deficiency have problems breaking down an amino acid called isoleucine from the food they eat.

Organic Acid DisordersThis 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 inheritedAcquiring 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 enzymesA 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 proteinA 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 2MBCD DEFICIENCY?

In order for the body to use protein from food, it is broken down into smaller parts called amino acidsAmino 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.

2MBCD deficiency is caused by problems with the enzyme “2-methylbutyryl-CoA dehydrogenase” (2MBCD). In people with 2MBCD deficiency, the 2MBCD enzyme is either missing or not working properly. This enzyme’s job is to help break down isoleucineThis 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.. When a child with 2MBCD deficiency eats food containing isoleucine, harmful substances may build up in the blood. Isoleucine is found in all foods that contain protein.

IF 2MBCD DEFICIENCY IS NOT TREATED, WHAT PROBLEMS OCCUR?

This condition is very rare. Only a small number of children with 2MBCD deficiency have been reported. The symptoms have been very severe in some children and mild or completely absent in others. It is likely that most babies found to have this condition through newborn screening will never develop symptoms.

Babies with 2MBCD deficiency have all been healthy at birth. A few babies started having symptoms just a few days after birth. Others had their first symptoms later in childhood. Some children have never had symptoms. Most infants with Hmong ancestry never develop symptoms.

In a few children, 2MBCD deficiency causes episodes of illness called metabolic crisisThis 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.. Some of the first symptoms of a metabolic crisis are:

• poor appetite
• extreme sleepiness or lack of energy
• irritable mood
• difficulty keeping warm

Other symptoms then follow:

• fever
• nausea
• vomiting
• low blood sugar called, hypoglycemiaThis happens when there is too little sugar (glucose) in the blood. It may cause a person to feel nervous, shaky, weak, or sweaty. It may also cause headache, blurred vision, and hunger. If left untreated, it can cause unconsciousness (coma) and sometimes even death.
• increased levels of acidic substances in the blood, called metabolic acidosisThis 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.

If a metabolic crisis is not treated, a child with 2MBCD deficiency can develop:

• breathing problems
• seizuresThese 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.
• comaThis 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

If not treated, episodes of metabolic crisis can cause brain damage. This can lead to life-long learning problems or intellectual disabilities.

Episodes of metabolic crisis can be triggered by:

• illness or infection
• going without food for long periods of time
• eating large amounts of protein

When a child is ill or goes without food for too long, the body breaks down its own protein and fatFat 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. to use for energy. In some children with 2MBCD deficiency, this can trigger a metabolic crisis.

Between episodes of metabolic crisis, children with 2MBCD deficiency are likely to be healthy.

Some children never have metabolic crises. Some may have other symptoms, though. These can include:

• poor growth
• tight, rigid muscles, called spasticityThis 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.
• involuntary movements, called choreoathetosisThis describes episodes of involuntary jerking movements combined with movements that are often irregular and twisting. These movements can flow from one body part to another. They commonly affect the arms, legs, trunk, and the muscles of the face.
• vision problems
• muscle weakness
• smaller head than normal (microcephalyThis is a head size that is too small for a child’s age. It is usually caused by lack of brain growth. It can happen for many reasons. Many children with microcephaly have intellectual disabilities.)
• delays in walking and other motor skills
• learning problems or intellectual disabilities

Some people with 2MBCD deficiency never have any symptoms and are only found to have the condition after a brother or sister is diagnosed, or they may be diagnosed through newborn screeningA 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..

WHAT IS THE TREATMENT FOR 2MBCD DEFICIENCY?

Some children diagnosed with 2MBCD deficiency through newborn screeningThe 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. will never have symptoms. These children may not need treatment.

Babies that do have symptoms may need lifelong treatment. If this is the case, your baby’s primary doctor may work with a metabolic doctor and a dietician to care for your child.

Prompt treatment may be needed to prevent metabolic crises and the health effects that follow. Certain treatments may be advised for some children but not others. Your doctor and metabolic doctor will decide whether your child needs treatment.

The following are treatments recommended for some babies and children with 2MBCD deficiency:

1.  Avoid going a long time without food
Some infants and young children with 2MBCD deficiency 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 dieticianThis 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. 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.

2. Low-protein diet, including medical foods and formula
A food plan low in protein is sometimes advised. Most food in the diet will be carbohydrates (bread, cereal, pasta, fruit, vegetables, etc.). CarbohydratesThis 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 can help prevent hypoglycemia and 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. It is important not to remove all protein from the diet. Children with 2MBCD deficiency need a certain amount of protein to grow properly.

If needed, your dietician will create a food plan that contains the right amount of protein, nutrients, and energy for your child. It is important to follow the advice of your dietician and metabolic doctor.

Medical foods and formula
There are medical foods such as special low-protein flours, pastas, and rice that are made especially for people with organic acid disorders. If needed, your dietician will tell you how to use these foods as part of your child’s diet.

In addition to a low-protein diet, some children are given a special medical formula that does not contain isoleucine. Your metabolic doctor and dietician will decide whether your child needs this formula. Some states offer help with payment for this formula, and others require private insurance to pay for the formula and other special medical foods.

3.  Medications
Some children may benefit by taking L-carnitineThis 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 body cells make energy. It also helps the body 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.  Do not use any medication without checking with your doctor.

4.  Call your doctor at the start of any illness
In some children, even minor illnesses such as a cold or the flu may lead to a metabolic crisis. In order to prevent problems, call your doctor right away when your child has any of the following:

• loss of appetite
• vomiting
• diarrhea
• infection or illness
• fever

Some children may need to eat more carbohydrates and drink more fluids when they are ill – even if they’re not hungry – or they could have a metabolic crisis. They may also need to avoid eating protein during any illness.

Children who are ill often don’t want to eat. If they can’t eat, or if they show signs of a metabolic crisis, they may need to be treated in the hospital.  Ask your metabolic doctor if you should carry a special travel letter with medical instructions for your child’s care.

WHAT HAPPENS WHEN 2MBCD DEFICIENCY IS TREATED?

With prompt and careful treatment, children with symptoms of 2MBCD deficiency have a good chance to live healthy lives with typical growth and development.

Despite treatment, some children may have repeated bouts of hypoglycemia or metabolic crises. This can cause brain damage and may lead to life-long learning problems or intellectual disabilities.

WHAT CAUSES THE 2MBCD ENZYME TO BE ABSENT OR NOT WORKING CORRECTLY?

Genes tell the body how to make enzymes. The ACADSB gene instructs the body to make the 2MBCD enzyme. Everyone has two copies of the ACADSB gene. People with 2MBCD deficiency have changes, also called variantsA 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 their ACADSB genesA 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.. Because of the variants in the ACADSB genes, the 2MBCD enzyme either does not work properly or is not made at all.

HOW IS 2MBCD DEFICIENCY INHERITED?

2MBCD deficiency is inherited in an autosomal recessive manner. It affects both boys and girls equally.

Everyone has two copies of the ACADSB genes that make the 2MBCD enzyme. In children with 2MBCD deficiency, neither of these ACADSB genes works correctly. These children inherit one non-working ACADSB gene from each parent.

Parents of children with 2MBCD deficiency rarely have the disorder. Instead, each parent has a single non-working ACADSB gene for 2MBCD deficiency. They are called carriersA 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 the condition 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 2MBCD deficiency. 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.

GeneticRelating to (or due to) genes and heredity or the field of studying genes and heredity. counseling is available to families who have children with 2MBCD deficiency. Genetic counselors can answer your questions about how the condition is inherited, choices during future pregnancies, and how to test other family members. Ask your doctor about a referral to a genetic counselorThese 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 for 2MBCD deficiency is available. Genetic testing, also called DNA testing, looks for changes, also called variants, in the ACADSB genes that causes 2MBCD deficiency. Talk with your genetic counselor or metabolic doctor if you have questions about DNADeoxyribonucleic 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. 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 confirm 2MBCD deficiency. Talk to your metabolic doctor if you have questions about testing for this condition.

CAN YOU TEST DURING A FUTURE PREGNANCY?

If both gene changes (variants) have been found in your child with 2MBCD deficiency, DNA testing can be done during future pregnancies. The sample needed for this test is obtained by either CVS or amniocentesisThis 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..

Parents may 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 2MBCD deficiency. 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 2MBCD DEFICIENCY OR BE CARRIERS?

Having 2MBCD deficiency
The brothers and sisters of a baby with 2MBCD deficiency have a chance of being affected, even if they haven’t had symptoms. Finding out whether other children in the family have the condition may be important. Early treatment may prevent serious health problems. Talk to your metabolic doctor or genetic counselor about whether your other children should be tested.

2MBCD deficiency carriers
Brothers and sisters who do not have 2MBCD deficiency still have a chance to be carriers like their parents. Except in special cases, carrier testing should only be done in people over 18 years of age.

If you are a parent of a child with 2MBCD deficiency, your brothers and sisters have a 50% chance to be a 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 2MBCD deficiency.

Some states do not provide newborn screening for 2MBCD deficiency. However, expanded newborn screening through private labs is available for babies born in states that do not screen for this condition. Your healthcare provider or genetic counselor can help you obtain expanded newborn screening.

When both parents are carriers, newborn screening 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 screening.

CAN OTHER FAMILY MEMBERS BE TESTED?

Diagnostic testing
Brothers and sisters of a child with 2MBCD deficiency can be tested using blood, urine, or skin samples.

Carrier testing
If both gene changes (variants) have been found in the child with 2MBCD deficiency, other family members can have DNA testing to see if they are carriers.

If DNA testing is not possible or is not helpful, other methods of carrier testing may be available. Your metabolic doctor or genetic counselor can answer your questions about carrier testing.

HOW MANY PEOPLE HAVE 2MBCD DEFICIENCY?

2MBCD deficiency is very rare. The actual incidence is unknown.

DOES 2MBCD DEFICIENCY HAPPEN MORE OFTEN IN A CERTAIN ETHNIC GROUP?

2MBCD deficiency is more common in the Hmong population from Southeast Asia and in Hmong-Americans. One in every 500 babies of Hmong ancestry is born with this condition.

DOES 2MBCD DEFICIENCY GO BY ANY OTHER NAMES?

2MBCD deficiency is sometimes also called:

• 2-methylbutyrylglycinuria
• Short/branched chain acyl-CoA dehydrogenase deficiency (SBCAD)
• 2-MBCD deficiency
• 2-MBAD deficiency
• 2MBAD deficiency
• SBCADD
• Short/branched-chain acyl-CoA dehydrogenase deficiency

WHERE CAN I FIND MORE INFORMATION?

Organic Acidemia Association
http://www.oaanews.org

Metabolic Support UK
https://www.metabolicsupportuk.org

MedlinePlus
https://medlineplus.gov/genetics/condition/short-branched-chain-acyl-coa-dehydrogenase-deficiency/

Baby’s First Test
http://www.babysfirsttest.org

DOCUMENT INFO:

Created by:	www.newbornscreening.info
Reviewed by:	HI, CA, OR, and WA metabolic specialists
Review date:	September 31, 2007 June 6, 2011 August 29, 2013 May 20, 2020 March 5, 2023
Update on:	March 5, 2023

 

DISCLAIMER:

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 MaternalHaving 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