What are the other Names for this Condition? (Also known as/Synonyms)

• ACAD8 Deficiency Disorder
• Deficiency of Acyl-CoaA Dehydrogenase Family, Member 8
• IBD Deficiency Disorder

What is Isobutyryl-CoA Dehydrogenase Deficiency Disorder? (Definition/Background Information)

• Isobutyryl-CoA Dehydrogenase Deficiency Disorder (IBD Deficiency Disorder) is an inborn error of valine (an amino acid) metabolism
• The symptoms, which may not develop until later in infancy or childhood, can include failure to thrive, dilated cardiomyopathy, seizures, and anemia
• IBD Deficiency Disorder is caused by mutations in the ACAD8 gene. It is inherited in an autosomal recessive manner
• Treatment may include the use of L-carnitine (a safe and natural substance that helps the body's cells make energy), frequent meals, and a low-valine diet

(Source: Isobutyryl-CoA Dehydrogenase Deficiency Disorder; Genetic and Rare Diseases Information Center (GARD) of National Center for Advancing Translational Sciences (NCATS), USA.)

Who gets Isobutyryl-CoA Dehydrogenase Deficiency Disorder? (Age and Sex Distribution)

• Isobutyryl-CoA Dehydrogenase Deficiency Disorder is a rare congenital disorder, whose exact prevalence is not known 
• The presentation of symptoms may occur at birth
• Both males and females may be affected
• Worldwide, individuals of all racial and ethnic groups may be affected

What are the Risk Factors for Isobutyryl-CoA Dehydrogenase Deficiency Disorder? (Predisposing Factors)

• A positive family history may be an important risk factor, since Isobutyryl-CoA Dehydrogenase Deficiency Disorder can be inherited
• Currently, no other risk factors have been clearly identified for this disorder

It is important to note that having a risk factor does not mean that one will get the condition. A risk factor increases one’s chances of getting a condition compared to an individual without the risk factors. Some risk factors are more important than others.

Also, not having a risk factor does not mean that an individual will not get the condition. It is always important to discuss the effect of risk factors with your healthcare provider.

What are the Causes of Isobutyryl-CoA Dehydrogenase Deficiency Disorder? (Etiology)

• Isobutyryl-CoA Dehydrogenase Deficiency Disorder is caused by mutations in the ACAD8 gene
• The ACAD8 gene provides instructions for making an enzyme that is responsible for processing valine, an amino acid that is part of many proteins
• If a mutation in the ACAD8 gene reduces or eliminates the activity of this enzyme, the body is unable to break down valine properly
• IBD Deficiency Disorder is inherited in an autosomal recessive manner

(Source: Isobutyryl-CoA Dehydrogenase Deficiency Disorder; Genetic and Rare Diseases Information Center (GARD) of National Center for Advancing Translational Sciences (NCATS), USA.)

Autosomal recessive mode of inheritance: Autosomal recessive conditions are traits or disorders that occur when two copies of an abnormal gene have been inherited on a non-sex chromosome. If both parents have an autosomal recessive condition, there is a 100% likelihood of passing on the mutated genes to their children. If, however, only one mutant copy of the gene is inherited, the individual will be a carrier of the condition, but will not be present with any symptoms. Children born to two carriers, have a 25% chance of being homozygous dominant (unaffected), a 50% chance of being heterozygous (carrier), and a 25% chance of being homozygous recessive (affected).

What are the Signs and Symptoms of Isobutyryl-CoA Dehydrogenase Deficiency Disorder?

The signs and symptoms of Isobutyryl-CoA Dehydrogenase Deficiency Disorder may include:

• Anemia
• Decreased plasma carnitine
• Dilated cardiomyopathy
• Muscular hypotonia

(Source: Isobutyryl-CoA Dehydrogenase Deficiency Disorder; Genetic and Rare Diseases Information Center (GARD) of National Center for Advancing Translational Sciences (NCATS), USA.)

• Failure to thrive
• Developmental delay

How is Isobutyryl-CoA Dehydrogenase Deficiency Disorder Diagnosed?

Isobutyryl-CoA Dehydrogenase Deficiency Disorder is diagnosed on the basis of the following information:

• Complete physical examination
• Thorough medical history evaluation
• Assessment of signs and symptoms
• Laboratory tests, including blood and urine acylcarnitine analyses
• Imaging studies
• Biopsy studies, if necessary
• Molecular genetic testing to check for or confirm causative gene mutation(s)

Many clinical conditions may have similar signs and symptoms. Your healthcare provider may perform additional tests to rule out other clinical conditions to arrive at a definitive diagnosis.

What are the possible Complications of Isobutyryl-CoA Dehydrogenase Deficiency Disorder?

The complications of Isobutyryl-CoA Dehydrogenase Deficiency Disorder may include:

• Delayed speech
• Frequent vomiting leading to severe dehydration requiring hospitalization
• Dilated cardiomyopathy leading to the following:
• Heart valve regurgitation
• Arrhythmia
• Edema
• Embolism 
• Sudden cardiac arrest
• Stroke

Complications may occur with or without treatment, and in some cases, due to treatment also.

How is Isobutyryl-CoA Dehydrogenase Deficiency Disorder Treated?

There is no cure for Isobutyryl-CoA Dehydrogenase Deficiency Disorder, since it is a genetic condition. The treatment is usually given to manage the signs and symptoms and any complications that develop, and may include:

• L-carnitine supplementation 
• Avoid fasting and eating frequently 
• Adhering to a low-valine food plan 

How can Isobutyryl-CoA Dehydrogenase Deficiency Disorder be Prevented?

Currently, Isobutyryl-CoA Dehydrogenase Deficiency Disorder may not be preventable, since it is a genetic disorder.

• Genetic testing of the expecting parents (and related family members) and prenatal diagnosis (molecular testing of the fetus during pregnancy), if available, may help in understanding the risks better during pregnancy
• If there is a family history of the condition, then genetic counseling will help assess risks, before planning for a child
• Active research is currently being performed to explore the possibilities for treatment and prevention of inherited and acquired genetic disorders

Regular medical screening at periodic intervals with tests and physical examinations are recommended.

What is the Prognosis of Isobutyryl-CoA Dehydrogenase Deficiency Disorder? (Outcomes/Resolutions) 

• The prognosis of Isobutyryl-CoA Dehydrogenase Deficiency Disorder is dependent upon the severity of the signs and symptoms and associated complications, if any
• Individuals with mild conditions have better prognosis than those with severe symptoms and complications
• Most affected children respond well to treatment, and eventually show normal development. However, lifelong treatment may be necessary
• Typically, the prognosis may be assessed on a case-by-case basis

Additional and Relevant Useful Information for Isobutyryl-CoA Dehydrogenase Deficiency Disorder:

The following DoveMed website link is a useful resource for additional information:

http://www.dovemed.com/diseases-conditions/rare-disorders/