Isovaleric acidemia is a rare disorder in which the body is unable to properly break down a particular protein building block (amino acid). The condition is classified as an organic acid disorder, which is a condition that leads to an abnormal buildup of particular acids known as organic acids. Abnormal levels of organic acids in the blood (organic acidemia), urine (organic aciduria), and tissues can be toxic and can cause serious health problems.

Normally, the body breaks down proteins from food into smaller parts called amino acids. Amino acids can be further processed to provide energy for growth and development. People with isovaleric acidemia have inadequate levels of an enzyme that helps break down a particular amino acid called leucine.

Health problems related to isovaleric acidemia range from very mild to life-threatening. In severe cases, the features of isovaleric acidemia become apparent within a few days after birth. The initial symptoms include poor feeding, vomiting, seizures, and lack of energy (lethargy). These symptoms sometimes progress to more serious medical problems, including seizures, coma, and possibly death. A characteristic sign of isovaleric acidemia is a distinctive odor of sweaty feet during acute illness. This odor is caused by the buildup of a compound called isovaleric acid in affected individuals.

In other cases, the signs and symptoms of isovaleric acidemia appear during childhood and may come and go over time. Children with this condition may fail to gain weight and grow at the expected rate (failure to thrive) and often have delayed development. In these children, episodes of more serious health problems can be triggered by prolonged periods without food (fasting), infections, or eating an increased amount of protein-rich foods.

Some people with gene mutations that cause isovaleric acidemia are asymptomatic, which means they never experience any signs or symptoms of the condition.

Isovaleric acidemia is estimated to affect at least 1 in 250,000 people in the United States.

Mutations in the IVD gene cause isovaleric acidemia. 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.

Genetic Testing Information

• Genetic Testing Registry: Isovaleryl-CoA dehydrogenase deficiency

Genetic and Rare Diseases Information Center

• Isovaleric acidemia

Patient Support and Advocacy Resources

• National Organization for Rare Disorders (NORD)

Clinical Trials

• ClinicalTrials.gov

Catalog of Genes and Diseases from OMIM

• ISOVALERIC ACIDEMIA; IVA

Scientific Articles on PubMed

• PubMed

• Ensenauer R, Fingerhut R, Maier EM, Polanetz R, Olgemoller B, Roschinger W, Muntau AC. Newborn screening for isovaleric acidemia using tandem mass spectrometry: data from 1.6 million newborns. Clin Chem. 2011 Apr;57(4):623-6. doi: 10.1373/clinchem.2010.151134. Epub 2011 Feb 18. Citation on PubMed
• Feinstein JA, O'Brien K. Acute metabolic decompensation in an adult patient with isovaleric acidemia. South Med J. 2003 May;96(5):500-3. doi: 10.1097/01.SMJ.0000051141.03668.1D. Citation on PubMed
• Grunert SC, Wendel U, Lindner M, Leichsenring M, Schwab KO, Vockley J, Lehnert W, Ensenauer R. Clinical and neurocognitive outcome in symptomatic isovaleric acidemia. Orphanet J Rare Dis. 2012 Jan 25;7:9. doi: 10.1186/1750-1172-7-9. Citation on PubMed or Free article on PubMed Central
• Vockley J, Ensenauer R. Isovaleric acidemia: new aspects of genetic and phenotypic heterogeneity. Am J Med Genet C Semin Med Genet. 2006 May 15;142C(2):95-103. doi: 10.1002/ajmg.c.30089. Citation on PubMed or Free article on PubMed Central