Isobutyryl-CoA dehydrogenase deficiency
ORGANIC ACID DISORDER
Disorder name: Isobutyryl-CoA dehydrogenase deficiency
Acronym: IBD deficiency
- What is IBD deficiency?
- What causes IBD deficiency?
- If IBD deficiency is not treated, what problems occur?
- What is the treatment for IBD deficiency?
- What happens when IBD deficiency is treated?
- What causes the isobutyryl-CoA dehydrogenase enzyme to be absent or not working correctly?
- How is IBD 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 IBD deficiency or be carriers?
- Can other family members be tested?
- How many people have IBD deficiency?
- Does IBD deficiency happen more often in a certain ethnic group?
- Does IBD deficiency go by any other names?
- Where can I find more information?
This fact sheet contains general information about IBD deficiency. Every child is different and some of these facts may not apply to your child specifically. At present, little is known about IBD deficiency, and there is no standard treatment plan. Certain treatments may be recommended for some children but not others. All children with IBD deficiency should be followed by a metabolic doctor in addition to their primary doctor.
WHAT IS IBD DEFICIENCY?
IBD stands for “isobutyryl-CoA dehydrogenase.” IBD deficiency has symptoms that are part of two different groups of conditions: organic acid disorders and fatty acid oxidationThis is the process used by the body to change fatty acids, the building blocks of fat, into energy. It happens in the mitochondria – the small energy-producing parts found in each cell of the body. disorders. Some children with IBD deficiency have problems breaking down an amino acid called valine 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.
|Fatty Acid Disorders:
Fatty acid oxidation disorders (FAODs)This is a group of rare inherited conditions. FAODs are caused by missing or non-working enzymes. Normally, many enzymes are used by the body to break down fat into energy. In people with FAODs, one of these enzymes is not working and fat cannot be used for energy. If these conditions are not treated, they can lead to serious health problems. are a group of rare inherited conditions. They are caused by enzymes that do not work properly.
A number of enzymes are needed to break down fats in the body (a process called fatty acid oxidation). Problems with any of these enzymes can cause a fatty acid oxidation disorder. People with FAODs cannot properly break down 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. from either the food they eat or from fat stored in their bodies.
The symptoms and treatment vary between different FAODs. They can also vary from person to person with the same FAOD. See the fact sheets for each specific FAOD.
FAODs are inherited in an autosomal recessive manner and affect both males and females.
WHAT CAUSES IBD DEFICIENCY?
In order for the body to use protein from the food we eat, 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.
IBD deficiency is caused by problems with the enzyme “isobutyryl-CoA dehydrogenase” (IBD). In people with IBD deficiency, the IBD enzyme is either missing or not working properly. This enzyme’s job is to help break down valineThis 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 IBD deficiency eats food containing valine, harmful substances build up in the blood and cause problems. Valine is found in all foods that contain protein.
IF IBD DEFICIENCY IS NOT TREATED, WHAT PROBLEMS OCCUR?
IBD deficiency is very rare and little is known about the effects. So far, symptoms have only been reported in a few children. Each child with IBD deficiency is likely to have somewhat different effects. Some children found to have IBD deficiency during 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. have never had symptoms.
It is likely that babies with IBD deficiency will be healthy at birth. In the first child reported to have IBD deficiency, symptoms began at one year of age.
- enlarged, weakened heart (called cardiomyopathyThis is a condition that causes the heart muscle to become weak and enlarged. These changes make it more difficult for the heart to pump blood. If not treated, it can be life-threatening. Some of the causes include certain metabolic disorders, viruses, alcohol, or a heart attack.)
- anemiaThis 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.
- poor growth
- low carnitine levels (a substance needed for the breakdown of fatty acidsThese 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.)
WHAT IS THE TREATMENT FOR IBD DEFICIENCY?
Your baby’s primary doctor will work with 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. and a dietician experienced with IBD deficiency to provide care for your child.
It is important to talk with a metabolic doctor about possible treatment as soon as you know your child has IBD deficiency. Certain treatments may be advised for some children but not others. Some treatments may be needed throughout life.
The following are treatments that may be recommended for some babies and children with IBD deficiency:
Children with IBD deficiency may be helped 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. L-carnitine may help prevent or treat heart problems and anemia in children with IBD deficiency. Do not use L-carnitine without checking with your doctor. Unless you are advised otherwise, use only L-carnitine prescribed by your doctor.
2. Avoid going a long time without food
Some infants and young children with IBD deficiency may be advised to eat frequently to prevent health effects. 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. Going without food for a long time causes the body to use its stores of fat and protein for energy. In some people with IBD deficiency, this may lead to the build up of harmful substances in the blood.
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 a feeding plan designed for your infant’s needs.
3. Low-valine food plan (including medical foods)
Most children with IBD deficiency seem to do fine without a change in diet. However, some children may be advised to eat a diet made up of foods low in valine. Valine is found in all foods that contain protein.
Foods high in protein that may need to be limited include:
- milk and dairy products
- meat and poultry
- dried beans and legumes
- nuts and peanut butter
There are medical foods such low-protein flours, pastas, rice, and special formulas that are made especially for people with organic acid disorders. Your dietician will let you know whether you should use these foods to supplement your child’s diet.
Some states offer help with payment for these medical foods and formula, and others require private insurance to pay for the formula and other special medical foods.
If you are advised to change your child’s diet, it is important not to remove all protein from the diet. Children need a certain amount to grow properly. Your dietician will create a food plan that contains the right amount of protein, nutrients, and energy to keep your child healthy.
WHAT HAPPENS WHEN IBD DEFICIENCY IS TREATED?
Although there is very little information available, it is thought that with prompt and careful treatment, children with IBD deficiency will be able to live healthy lives with typical growth and development. Treatment with carnitine may reverse the heart problems and anemia and may improve growth.
WHAT CAUSES THE IBD ENZYME TO BE ABSENT OR NOT WORKING CORRECTLY?
Genes tell the body how to make enzymes. The ACAD8 gene instructs the body to make the IBD enzyme. Everyone has two copies of the ACAD8 gene. People with IBD 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 ACAD8 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 ACAD8 genes, the IBD enzyme either does not work properly or is not made at all.
HOW IS IBD DEFICIENCY INHERITED?
IBD deficiency is inherited in an autosomal recessive manner. It affects both boys and girls equally.
Everyone has two copies of the ACAD8 gene that make the isobutyryl-CoA dehydrogenase enzyme. In children with IBD deficiency, neither of their ACAD8 genes works correctly. These children inherit one non-working ACAD8 gene from each parent.
Parents of children with IBD deficiency rarely have the disorder. Instead, each parent has a single non-working ACAD8 gene for IBD 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 IBD deficiency because the other gene of this pair is working correctly.
When both parents are carriers, there is a 25% chance in each pregnancy for the child to have IBD 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 IBD deficiency. Genetic counselors can answer your questions about how IBD deficiency 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 IBD deficiency is available. Genetic testing, also called DNA testing, looks for changes (variants) in the ACAD8 genes that causes IBD 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 IBD deficiency. Talk to your metabolic doctor or genetic counselor if you have questions about testing for IBD deficiency.
CAN YOU TEST DURING A FUTURE PREGNANCY?
If both gene changes have been found in your child with IBD 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 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 IBD 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 IBD DEFICIENCY OR BE CARRIERS?
Having IBD deficiency
The brothers and sisters of a baby with IBD deficiency have a small chance of being affected, even if they haven’t had symptoms. Finding out whether other children in the family have this condition is important because early treatment may prevent serious health problems. Talk to your metabolic doctor or genetic counselor about testing your other children.
IBD deficiency carriers
Brothers and sisters who do not have IBD 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 IBD 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 IBD deficiency.
Some states do not provide newborn screening for IBD deficiency. However, expanded 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. 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 IBD deficiency 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?
To make sure they do not have the condition, brothers and sisters of a child with IBD deficiency can be tested using blood, urine, or skin samples.
If both gene changes (variants) have been found in the child with IBD deficiency, other family members can have DNA testing to see if they are carriers.
If DNA testing is not possible or would not be 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 IBD DEFICIENCY?
IBD deficiency is very rare. Less than 70 people have been reported in the medical literature, and most people with IBD deficiency have no symptoms. The actual incidence is unknown.
DOES IBD DEFICIENCY HAPPEN MORE OFTEN IN A CERTAIN ETHNIC GROUP?
IBD deficiency does not happen more often in any specific race, ethnic group, geographical area, or country.
DOES IBD DEFICIENCY GO BY ANY OTHER NAMES?
IBD deficiency is sometimes also called:
- Acyl-CoA dehydrogenase family, member 8
- ACAD8 deficiency
WHERE CAN I FIND MORE INFORMATION?
Organic Acidemia Association
Metabolic Support UK
Baby’s First Test
|Reviewed by:||HI, CA, OR, and WA metabolic specialists|
|Review date:||September 31, 2007
June 6, 2011
August 29, 2013
May 18, 2020
March 5, 2023
|Update on:||March 5, 2023|
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