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Genetics Home Reference: your guide to understanding genetic conditions
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Isovaleric acidemia

Reviewed April 2007

What is isovaleric acidemia?

Isovaleric acidemia is a rare disorder in which the body is unable to process certain proteins properly. It 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.

How common is isovaleric acidemia?

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

What genes are related to isovaleric acidemia?

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.

Related Gene(s)

Changes in this gene are associated with isovaleric acidemia.

  • IVD

How do people inherit isovaleric acidemia?

This condition 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.

Where can I find information about diagnosis or management of isovaleric acidemia?

These resources address the diagnosis or management of isovaleric acidemia and may include treatment providers.

  • Baby's First Test (http://www.babysfirsttest.org/newborn-screening/conditions/isovaleric-acidemia)
  • Gene Review: Organic Acidemias Overview (http://www.ncbi.nlm.nih.gov/books/NBK1134)
  • Genetic Testing Registry: Isovaleryl-CoA dehydrogenase deficiency (http://www.ncbi.nlm.nih.gov/gtr/conditions/C0268575)

You might also find information on the diagnosis or management of isovaleric acidemia in Educational resources (http://www.ghr.nlm.nih.gov/condition/isovaleric-acidemia/show/Educational+resources) and Patient support (http://www.ghr.nlm.nih.gov/condition/isovaleric-acidemia/show/Patient+support).

General information about the diagnosis (http://ghr.nlm.nih.gov/handbook/consult/diagnosis) and management (http://ghr.nlm.nih.gov/handbook/consult/treatment) of genetic conditions is available in the Handbook. Read more about genetic testing (http://ghr.nlm.nih.gov/handbook/testing), particularly the difference between clinical tests and research tests (http://ghr.nlm.nih.gov/handbook/testing/researchtesting).

To locate a healthcare provider, see How can I find a genetics professional in my area? (http://ghr.nlm.nih.gov/handbook/consult/findingprofessional) in the Handbook.

Where can I find additional information about isovaleric acidemia?

You may find the following resources about isovaleric acidemia helpful. These materials are written for the general public.

You may also be interested in these resources, which are designed for healthcare professionals and researchers.

What other names do people use for isovaleric acidemia?

  • Isovaleric acid-CoA dehydrogenase deficiency
  • Isovaleryl-CoA dehydrogenase deficiency
  • IVA
  • IVD deficiency

For more information about naming genetic conditions, see the Genetics Home Reference Condition Naming Guidelines (http://ghr.nlm.nih.gov/ConditionNameGuide) and How are genetic conditions and genes named? (http://ghr.nlm.nih.gov/handbook/mutationsanddisorders/naming) in the Handbook.

What if I still have specific questions about isovaleric acidemia?

Ask the Genetic and Rare Diseases Information Center (http://rarediseases.info.nih.gov/GARD/).

What glossary definitions help with understanding isovaleric acidemia?

acids ; aciduria ; acute ; amino acid ; asymptomatic ; autosomal ; autosomal recessive ; cell ; CoA ; coma ; compound ; deficiency ; dehydrogenase ; enzyme ; failure to thrive ; fasting ; gene ; inherited ; lethargy ; leucine ; mutation ; nervous system ; newborn screening ; organic acid ; protein ; recessive ; screening ; sign ; toxic

You may find definitions for these and many other terms in the Genetics Home Reference Glossary (http://www.ghr.nlm.nih.gov/glossary).

References

  • Feinstein JA, O'Brien K. Acute metabolic decompensation in an adult patient with isovaleric acidemia. South Med J. 2003 May;96(5):500-3. (http://www.ncbi.nlm.nih.gov/pubmed/12911192?dopt=Abstract)
  • 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. Review. (http://www.ncbi.nlm.nih.gov/pubmed/16602101?dopt=Abstract)

 

The resources on this site should not be used as a substitute for professional medical care or advice. Users seeking information about a personal genetic disease, syndrome, or condition should consult with a qualified healthcare professional. See How can I find a genetics professional in my area? (http://ghr.nlm.nih.gov/handbook/consult/findingprofessional) in the Handbook.

 
Reviewed: April 2007
Published: October 20, 2014