Pin Me

A Guide To Isovaleric Acidemia

written by: bjlbyron•edited by: lrohner•updated: 11/17/2010

Isovaleric acidemia is a genetic disorder that prevents the body from properly breaking down ingested proteins. Read on to learn about the life-threatening symptoms that individuals who have this condition sometimes experience and what is known about its underlying genetic cause.

  • slide 1 of 3

    What Is Isovaleric Acidemia?

    Proteins are comprised of amino acids which our bodies use in synthesizing other proteins and as an energy source for normal growth and development. Healthy individuals break down proteins shortly after ingesting them. Individuals who suffer from isovaleric acidemia (IA), a rare inherited disorder that affects about 1 in every 250,000 or so people, cannot break down proteins properly. As a result, excessive levels of organic acids build up in the blood, urine and throughout the rest of the body.

    Symptoms experienced by those who have IA range from very minor to life-threatening. In some cases, symptoms arise near the time of birth. Symptoms commonly seen at this time include refusal to eat, vomiting, frequent fussiness, extreme tiredness and even seizures, among others. In the worst of cases, whether in infancy, adolescence, or adulthood, coma and even death occurs.

    In many instances, symptoms are mild and can even disappear completely for long periods of time. In some affected individuals, symptoms are alleviated in childhood and never return again.

    A hallmark sign of IA is a putrid, sweaty odor that is released from the body, especially at times when other symptoms are at their worst. Specifically, this sweaty odor is due to the build up of abnormal levels of a compound that is known as isovaleric acid.

  • slide 2 of 3

    What Is Known About The Underlying Genetic Cause of Isovaleric Acidemia?

    After much research, human molecular geneticists determined that mutations in a gene designated IVD are causative of IA. The IVD gene encodes a protein that plays a role in helping the body to break down the proteins that we ingest in the foods that we eat. In particular, the protein that is encoded by IVD acts by processing leucine, which is one of the 20 different types of amino acids that are part of proteins.

    Individuals who have IA have mutations in both of their IVD genes (IA therefore is an autosomal recessive genetic disorder). These individuals either do not make the protein that is encoded by the IVD gene or they make defective copies of that protein. In either event, these individuals therefore cannot process leucine. As a result, isovaleric acid builds up in throughout the body to abnormally high levels, an occurrence which leads to the symptoms described above.

    Interestingly, individuals who harbor mutations in both copies of their IVD genes, but who never show any signs of IA, have been identified. It is believed, therefore, that the particular mutations that these people carry simply are not severe enough in nature to significantly affect the protein that is encoded for by the IVD gene.

    This article is only meant to provide some basic information regarding the genetic condition known as isovaleric acidemia. If you have any further questions regarding this inherited disorder, please contact your doctor or consult a genetic counselor.

  • slide 3 of 3


    Genetics Home Reference, National Institutes of Health, Isovaleric acidemia:

    Genetics Home Reference, National Institutes of Health, IVD:

    J. Vockley and R. Ensenauer, Isovaleric Acidemia: New Aspects of Genetic and Phenotypic Heterogeneity, American Journal of Medical Genetics 142C:95-103 (2006).