isovaleric acidemia

What Is Isovaleric Acidemia?

Isovaleric Acidemia (IVA), caused by mutations in the IVD gene, is an inherited disorder in which an enzyme that breaks down the amino acid leucine does not function properly resulting in accumulation isovaleric acid in the blood. High levels of isovaleric acid in the blood can be toxic and result in damage to the brain and nervous system. IVA can result in seizures, coma, or other nervous system disorders. IVA can also be life-threatening. However, with early diagnosis and treatment, individuals with IVA are more likely to have improved growth, development, and life expectancy.

There are three forms of IVA. The severe, neonatal form has its onset during the first weeks of life. The childhood-onset form occurs episodically in childhood, in response to stress. The mild form may never result in symptoms of IVA.

Neonatal Isovaleric Acidemia

Symptoms of the neonatal form are often observed in the first few weeks after birth and include feeding problems, high acidity of the blood and urine, and difficulty in maintaining proper body temperature. Untreated IVA can eventually result in bleeding of the brain (cerebral hemorrhage), seizures, and death.

Childhood Isovaleric Acidemia

Symptoms of the childhood form of IVA are often observed at about 12 months of age. These symptoms are similar to the neonatal form but are triggered by stresses such as illness, fasting, or high-protein diets. In the absence of stresses to the body, there may be no symptoms. However, children with childhood IVA may have learning problems, reduced growth, and muscle weakness.

Mild Form

Some individuals with specific mutations in the IVD gene do not have symptoms of neonatal or childhood IVA. Some of these individuals do develop mild developmental delay. It is not yet clear why these changes in the IVD gene do not cause other IVA symptoms.

How Common Is Isovaleric Acidemia?

The prevalence of IVA is 1 in 250,000 in the American population. The incidence of IVA is about 1 in 62,000 in the German population.

How Is Isovaleric Acidemia Treated?

Individuals with IVA need a special diet, which is low in leucine and contains proteins. For example, infants may be treated with a leucine-free formula. The supplements carnitine and glycine can reduce the toxicity of isovaleric acid and aid in its removal from the body.

Individuals with IVA need close monitoring by a physician during times of illness and may need to ensure adequate hydration and adopt a diet high in carbohydrates. Symptoms such as vomiting, diarrhea, and illness with a fever may require prompt treatment.

Frequent monitoring of individuals with IVA is important to determine that proper growth, metabolism, and development is ongoing.

What Is the Prognosis for a Person with Isovaleric Acidemia?

Without early diagnosis and treatment, individuals with IVA may have damage to the brain and nervous system, intellectual and developmental disability, or in severe cases, death. If a person with IVA receives treatment, they are more likely to reach normal levels of growth, development, and intellectual ability. However, some individuals may experience a reduction in growth and development, learning disabilities, or even death, due to periodic episodes of high levels of isovaleric acid, primarily in response to stress. As a person with IVA ages, the frequency of such episodes decreases.

Individuals with IVA without symptoms are more likely to live a normal lifespan.