Isovaleric Acidemia

What is isovaleric acidemia?

Isovaleric acidemia is a subtype of organic acidemia in which individuals have problems breaking down parts of the food they eat. Normally, the body breaks down proteins from food into amino acids. People with isovaleric acidemia don’t have enough of an enzyme that helps to break down the amino acid called leucine. Isovaleric acidemia can either be acute (sudden and short-term) or chronic (a long-developing syndrome) and intermittent. In some cases, symptoms begin within a few days of birth, but they can also appear during childhood and may come and go over time. It is estimated to affect 1 in 250,000 people in the United States.

What are the symptoms of isovaleric acidemia?

Symptoms can range from very mild to life-threatening. They include:

Vomiting
Lack of appetite
Listlessness
A distinctive odor of sweaty feet (caused by the buildup of the compound isovaleric acid in the individual)
Low body temperature
Developmental delay
Seizures
Coma

Some people with the genetic mutations that cause isovaleric acidemia are asymptomatic, meaning they never experience any symptoms of the condition.

What causes isovaleric acidemia?

Isovaleric acidemia is inherited in an autosomal recessive pattern, which means that a mutated version of the gene had to be passed down from both parents in order for them to have the disease. Mutations in the IVD gene cause isovaleric acidemia. This gene makes an enzyme called isovaleryl CoA dehydrogenase. That enzyme breaks down leucine, which is a part of many proteins. A mutation in the IVD gene could reduce or eliminate the activity of this enzyme, which would keep the body from breaking down leucine properly. Because of this, an organic acid called isovaleric acid and other compounds build up to harmful levels, which damages the brain and nervous system.

How is isovaleric acidemia diagnosed?

Isovaleric acidemia is diagnosed using the following procedures:

Before birth, by:
- Measuring the concentration of abnormal metabolites in amniotic fluid
- Measuring the activity of the enzyme isovaleryl-CoA dehydrogenase in fluid or tissue samples from the fetus or uterus
- Amniocentesis: taking and analyzing a sample of fluid surrounding the developing fetus
- Chorionic villus sampling (CVS): Removing and examining the tissue from a portion of the placenta.
At birth, through expanded newborn screening with tandem mass spectrometry
Clinical evaluation
Detailed recordings of patient and family medical history
A variety of specialized tests
Laboratory studies of white blood cells and cultured skin cells to confirm deficiency of the isovaleryl-CoA dehydrogenase enzyme

What are the treatments for isovaleric acidemia?

Isovaleric acidemia treatment includes, but is not limited to:

Moderate restrictions of proteins (especially the amino acid leucine) in the diet
Supplementation of glycine and L-carnitine, which help to rid the body of excess isovaleric acid
Genetic counseling

Where can I find out more about isovaleric acidemia?