Isobutyryl-coenzyme A dehydrogenase deficiency

Isobutyryl-coenzyme A dehydrogenase deficiency, is a rare metabolic disorder in which the body is unable to process certain amino acids properly.

People with this disorder have inadequate levels of an enzyme that helps break down the amino acid valine, resulting in a buildup of valine in the urine, a symptom called valinuria.

Genetics

Isobutyryl-coenzyme A dehydrogenase deficiency has an autosomal recessive pattern of inheritance.

Defects in the ACAD8 gene cause isobutyryl-coenzyme A dehydrogenase deficiency. The ACAD8 gene provides instructions for making an enzyme that plays an essential role in breaking down proteins from the diet. Specifically, the enzyme 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. As a result, poor growth and reduced energy production may occur.

This disorder is inherited in an autosomal recessive pattern, which means the defective gene is located on an autosome, and two copies of the gene - one from each parent - are needed to be born with the disorder. The parents of an individual with an autosomal recessive disorder are carriers of one copy of the defective gene, but do not show signs and symptoms of the disorder.

Symptoms Infants with IBD deficiency usually appear healthy at birth. Some children identified with the condition through newborn screening never develop symptoms. When symptoms do occur, they tend to vary, but may include poor feeding and growth (failure to thrive), a weakened and enlarged heart (dilated cardiomyopathy), seizures, and low numbers of red blood cells (anemia). Another feature of this disorder may be very low blood levels of carnitine (a natural substance that helps convert certain foods into energy). IBD deficiency may be worsened by long periods without food (fasting) or infections that increase the body's demand for energy.

For most diseases, symptoms will vary from person to person. People with the same disease may not have all the symptoms listed. 30%-79% of people have these symptoms

• Decreased plasma carnitine
• Dicarboxylic aciduria
• Elevated plasma acylcarnitine levels

5%-29% of people have these symptoms

• Dehydration
• Delayed speech and language development(Deficiency of speech development)
• Dilated cardiomyopathy(Stretched and thinned heart muscle)
• Ketotic hypoglycemia
• Mild global developmental delay
• Muscular hypotonia(Low or weak muscle tone)
• Pulmonic stenosis(Narrowing of pulmonic valve)
• Vomiting(Throwing up)

Diagnosis

Babies with this disorder are usually healthy at birth. The signs and symptoms may not appear until later in infancy or childhood and can include poor feeding and growth (failure to thrive), a weakened and enlarged heart (dilated cardiomyopathy), seizures, and low numbers of red blood cells (anemia). Another feature of this disorder may be very low blood levels of carnitine (a natural substance that helps convert certain foods into energy).

Isobutyryl-CoA dehydrogenase deficiency may be worsened by long periods without food (fasting) or infections that increase the body's demand for energy. Some individuals with gene mutations that can cause isobutyryl-CoA dehydrogenase deficiency may never experience any signs and symptoms of the disorder.

Treatment

• There is no standard treatment protocol for IBD deficiency. Infants diagnosed through newborn screening are encouraged to work with a metabolic disease specialist and a dietician experienced in metabolic disorders. Some treatments may be recommended even if no symptoms have been observed. Treatment may be needed throughout life. The following treatments may be recommended for some babies and children with IBD deficiency.
• 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.

See also

• Isobutyryl-coenzyme A

External links

Classification	OMIM: 604773 DiseasesDB: 34225

• Isobutyryl-coenzyme A dehydrogenase deficiency at NLM Genetics Home Reference