Isovaleric acidemia

Isovaleric acidemia is caused by mutations in the IVD gene. The IVD gene provides instructions for making an enzyme that plays an essential role in breaking down proteins from the diet. Specifically, this enzyme helps process the amino acid leucine, which is part of many proteins. If a mutation in the IVD gene reduces or eliminates the activity of this enzyme, the body is unable to break down leucine properly. As a result, an organic acid called isovaleric acid and related compounds build up to harmful levels in the body. This buildup damages the brain and nervous system, causing serious health problems.

Isovaleric acidemia is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.

At conception, each sibling of a person with isovaleric acidemia has a 25% (1 in 4) chance of being affected, a 50% chance of being an asymptomatic carrier, and a 25% chance of being unaffected and not a carrier. Once an at-risk sibling is known to be unaffected, the risk for him/her to be a carrier is about 67% (2 in 3). Carriers typically do not show signs and symptoms of the condition.

Isovaleric acidemia (IVA) is a type of organic acid disorder in which affected individuals have problems breaking down an amino acid called leucine from the food they eat. Signs and symptoms may range from very mild to life-threatening. In severe cases, symptoms begin within a few days of birth and include poor feeding, vomiting, seizures, and lack of energy (lethargy); these may progress to more serious medical problems including seizures, coma, and possibly death. In other cases, signs and symptoms appear during childhood and may come and go over time. A characteristic sign of IVA is a distinctive odor of sweaty feet during acute illness. Other features may include failure to thrive or delayed development. IVA is caused by mutations in the IVD __ gene and is inherited in an autosomal recessive manner. Treatment involves moderate restriction of proteins in the diet and oral administration of glycine and L-carnitine which helps to rid the body of excess isovaleric acid.

Some individuals with gene mutations that are known to cause isovaleric acidemia (IVA) never experience any signs of the condition. Individuals who are diagnosed and do have signs and symptoms of IVA technically have the condition throughout life, although depending on the form of the condition, signs and symptoms may come and go over time.

There are two recognized forms of IVA that cause symptoms. One is the acute neonatal form, in which signs and symptoms begin shortly after birth. This form often leads to severe metabolic acidosis in the first days of life, followed by death. The other form is a "chronic- intermittent" form, usually starting later in infancy or early childhood. Individuals with this form experience periods of metabolic crises with intervening periods of being asymptomatic (not having any symptoms). Between episodes of metabolic crisis, children with IVA are usually healthy. In general, for both forms (when infants with the acute form survive the neonatal period), episodes of metabolic crises tend to occur frequently in early infancy and young childhood, but the frequency usually diminishes as an affected individual ages. With appropriate therapy, the long term prognosis for affected individuals is good.

There is currently no cure for isovaleric acidemia (IVA). Upon diagnosis, immediate treatment is typically necessary in order to prevent metabolic crises and complications that may follow. It is often recommended that affected individuals have a low-leucine / low-protein diet and use medical foods (such as special low-protein flours, pastas, and rice that are made especially for people with organic acid disorders) and leucine-free medical formula. A dietician with knowledge of IVA can help parents create a food plan that contains the right amount of protein, nutrients, and energy to keep the child healthy. Any diet changes should be under the guidance of a dietician. Medications that may be recommended include glycine and L-carnitine, which help rid the body of unwanted isovaleric acid and other harmful substances. No medication or supplement should be used without checking with a metabolic doctor. Children with symptoms of a metabolic crisis need medical treatment right away and may be given bicarbonate, glucose, and other medications by IV.

With prompt and careful treatment, children with IVA have a good chance to live healthy lives with normal growth and development. However, some children, even when treated, may have repeated metabolic crises which can lead to life- long learning problems or intellectual disability.

The Newborn Screening Coding and Terminology Guide has information on the standard codes used for newborn screening tests. Using these standards helps compare data across different laboratories. This resource was created by the National Library of Medicine.