Isovaleric acidemia

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief:

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Isovaleric acidemia is a rare genetic disorder in which the body is unable to process certain proteins properly. People with this disorder have inadequate levels of an enzyme that helps break down the amino acid leucine. It is closely related to the genetic metabolic disorder Maple syrup urine disease.

Isovaleric acidemia is estimated to affect at least 1 in 250,000 births in the United States. The condition is inherited in an autosomal recessive pattern, caused by mutations in both copies of the IVD gene.

The enzyme encoded by IVD, isovaleric acid-CoA dehydrogenase (EC 1.3.99.10), plays an essential role in breaking down proteins from the diet. Specifically, the enzyme is responsible for the third step in processing leucine, an amino acid that 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, a molecule called isovaleric acid and related compounds build up to harmful levels, damaging the brain and nervous system.

A characteristic feature of isovaleric acidemia is a distinctive odor of sweaty feet. This odor is caused by the buildup of a compound called isovaleric acid in affected individuals.

In about half of cases, the signs and symptoms of this disorder become apparent within a few days after birth and include poor feeding, vomiting, seizures, and lack of energy that can progress to coma. These medical problems are typically severe and can be life-threatening. In the other half of cases, the signs and symptoms of the disorder appear during childhood and may come and go over time. They are often triggered by an infection or by eating an increased amount of protein-rich foods.

The urine of newborn can be screened with mass spectrometry for isovaleric acid, allowing for presymptomatic diagnosis.

• Methylmalonic acidemia
• Propionic acidemia

• Organic Acidemia Association
• Isovaleric acidemia at NLM Genetics Home Reference
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• Budd, M. A. et al. Isovaleric acidemia: clinical feature of a new genetic defect of leucine metabolism. New Eng. J. Med. 277: 321-327, 1967. PMID 4378266
• National Library of Medicine. Genetics Home Reference: Isovaleric acidemia

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