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 genteic metabolic disorder Maple syrup urine disease. A genetic disorder, or genetic disease is a disease caused, at least in part, by the genes of the person with the disease. ... A representation of the 3D structure of myoglobin, showing coloured alpha helices. ... Leucine is one of the 20 most common amino acids on Earth, and coded for by DNA. Its chemical composition is identical to that of isoleucine, but its atoms are arranged differently resulting in different properties. ...

Symptoms

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. Vomiting (or emesis) is the forceful expulsion of the contents of ones stomach through the mouth. ... This article is about the medical condition. ... Fatigue is a feeling of excessive tiredness or lethargy, with a desire to rest, perhaps to sleep. ... For other meanings of the word coma, especially in astronomy, see coma (disambiguation) In medicine, a coma is a profound state of unconsciousness, which may result from a variety of conditions including intoxication (drug, alcohol or toxins), metabolic abnormalities (hypoglycemia, hyperglycemia, ketoacidosis, etc. ...

The urine of newborn can be screened with mass spectrometry for isovaleric acid, allowing for presymptomatic diagnosis. Mass spectrometry is a technique for separating ions by their mass-to-charge (m/z) ratios. ...

Genetics

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 United States of America — also referred to as the United States, the U.S.A., the U.S., America, the States, or (archaically) Columbia—is a federal republic of 50 states located primarily in central North America (with the exception of two states: Alaska and Hawaii). ... In genetics, the term recessive gene refers to an allele that causes a phenotype (visible or detectable characteristic) that is only seen in a homozygous genotype (an organism that has two copies of the same allele). ... This stylistic schematic diagram shows a gene in relation to the double helix structure of DNA and to a chromosome (right). ...

The enzyme encoded by IVD, isovaleric acid-CoA dehydrogenase, 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.

References

• 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 (http://ghr.nlm.nih.gov/condition=isovalericacidemia?wf=1)