Isobutyryl-CoA dehydrogenase (IBD) deficiency is a condition that disrupts the breakdown of certain proteins. Normally, proteins from food are broken down into parts called amino acids. Amino acids can be further processed to provide energy for growth and development. People with IBD deficiency have inadequate levels of an enzyme that helps break down a particular amino acid called valine.

Most people with IBD deficiency are asymptomatic, which means they do not have any signs or symptoms of the condition. A few children with IBD deficiency have developed features such as a weakened and enlarged heart (dilated cardiomyopathy), weak muscle tone (hypotonia), and developmental delay. This condition may also cause low numbers of red blood cells (anemia) and very low blood levels of carnitine, which is a natural substance that helps convert certain foods into energy. The range of signs and symptoms associated with IBD deficiency remains unclear because very few affected individuals have been reported.

Mutations in the ACAD8 gene cause IBD deficiency. This gene provides instructions for making the IBD enzyme, which is involved in breaking down valine. ACAD8 gene mutations reduce or eliminate the activity of the IBD enzyme. As a result, valine is not broken down properly. Impaired processing of valine may lead to reduced energy production and the features of IBD deficiency.

Normal Function

The ACAD8 gene provides instructions for making an enzyme called isobutyryl-CoA dehydrogenase (IBD). This enzyme is found in mitochondria, the energy-producing centers inside cells. The IBD enzyme is involved in breaking down proteins from food. Specifically, this enzyme is responsible for the third step in the breakdown of a protein building block (amino acid) called valine. The IBD enzyme converts a molecule called isobutyryl-CoA into a molecule called methylacrylyl-CoA. Other enzymes further break down methylacrylyl-CoA into molecules that cells can use for energy.

Health Conditions Related to Genetic Changes

Isobutyryl-CoA dehydrogenase deficiency

At least 19 mutations in the ACAD8 gene have been found to cause isobutyryl-CoA dehydrogenase (IBD) deficiency. Some of these mutations reduce the activity of the IBD enzyme, while other mutations prevent the gene from producing any functional enzyme. As a result, valine is not broken down properly. An inability to process valine may lead to reduced energy production and the features of IBD deficiency.

Other Names for This Gene

• ACAD-8
• ACAD8_HUMAN
• Activator-recruited cofactor 42 kDa component
• acyl-CoA dehydrogenase family, member 8
• acyl-coenzyme A dehydrogenase 8
• ARC42
• FLJ22590

Genomic Location

IBD deficiency is a genetic condition. Babies inherit it from their biological (birth) parents.

• IBD deficiency is usually an autosomal recessive condition. Babies inherit the condition when each parent passes down a nonworking ACAD8 gene to their baby. Only babies with two nonworking ACAD8 genes—one from the mom and one from the dad—have this condition.
  • People with one working copy and one nonworking copy of the ACAD8 gene are called carriers.
  • Carriers do not have or develop the condition. However, they may pass down a nonworking copy of the gene to their children.
  • If two parents are carriers of a nonworking copy of the ACAD8 gene, they have a 1 in 4 chance of having a child with IBD deficiency.
  • Carriers for IBD deficiency often do not know they are carriers before having a child with the condition. In most cases, families have no history of the condition until the birth of a child with IBD deficiency.
  • Parents who already have a child with IBD deficiency due to a change in the ACAD8 gene still have a 1 in 4 chance of having another child with IBD deficiency. This 1 in 4 chance stays the same for all future children.
• Genetic counselors and medical geneticists can help families learn about this condition and the chance of having children with it.

Most babies and children with IBD deficiency will have no signs or symptoms. In very rare cases, some children may have the following signs:

• Floppy legs and arms (hypotonia)
• Weak and large heart (cardiomyopathy)
• Low number of red blood cells (anemia)
• Low levels of carnitine in the blood

Newborn screening for IBD deficiency is done using a small amount of blood collected from your baby’s heel. During screening, a special machine measures how much of certain substances (called acylcarnitines) are in your baby’s blood. The body produces these substances when it breaks down food. Babies with high levels of these substances might have IBD deficiency.

What Happens After an Out-of-Range Screening Result?

If your baby’s blood spot screening result for IBD deficiency is out-of-range, your baby’s health care provider will contact you. Together, you will discuss next steps and follow-up plans.

An out-of-range screening result does not mean that your baby definitely has the condition. It does mean that your baby needs more follow-up testing.

Your baby may need the following tests after an out-of-range screening result:

• Blood and/or urine tests
• Genetic testing using a blood sample

You should complete any recommended follow-up testing as soon as possible.

False-positive newborn screening results for this condition can happen. Babies given carnitine might have false-positive results for this condition.

Newborn screening helps babies lead healthier lives. If your baby has an out-of-range result, follow up with your health care provider quickly. It is important to follow their instructions. In some cases, your baby’s health care provider may decide it is best to watch (monitor) your baby to decide next steps.

• Children with IBD deficiency may be helped by taking L-carnitine, a safe and natural substance which helps the body's cells make energy and get rid of harmful wastes. L-carnitine may also help to prevent or treat the heart problems and anemia seen in children with IBD deficiency.
• Some infants and children with IBD deficiency may be advised to avoid fasting. 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. Eating frequently (every 4 to 6 hours) may help to avoid these health effects.
• While most children with IBD deficiency do fine without a change in diet, a low-valine food plan might be necessary. Valine is found in all foods with protein. Foods high in valine, such as dairy products, meat, poultry, fish, eggs, dried beans and legumes, nuts and peanut butter should be limited. 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 / physician can advise you on whether you should use these foods to supplement your child’s diet.