Do carriers of a single IVD mutation experience any health problems?

Most heterozygous carriers are asymptomatic because one functional copy of the gene provides enough enzyme activity, though rare cases may show mild, transient metabolic sensitivity during extreme catabolic stress.===

What signs should prompt an emergency visit for a child with isovaleric acidemia?

Rapid onset of vomiting, lethargy, seizures, a “sweaty‑feet” odor, or unexplained acidosis are red‑flag symptoms; immediate treatment with intravenous glucose, bicarbonate, and possibly carnitine is required.

How is isovaleric acidemia diagnosed in a newborn?

Newborn screening programs measure specific organic acids in dried blood spots; an elevated isovalerylcarnitine (C5) triggers confirmatory urine organic acid analysis and enzyme activity testing for isovaleryl‑CoA dehydrogenase.

What dietary changes can reduce the risk of metabolic crises in patients with IVD mutations?

low‑leucine diet that limits high‑protein foods (e.g., meat, dairy, legumes) and provides specialized medical formulas helps keep isovaleryl‑CoA levels low; regular monitoring of plasma leucine and urine organic acids guides adjustments.

IVD gene

The IVD gene encodes the enzyme isovaleryl‑CoA dehydrogenase, which is essential for breaking down the amino acid leucine. Mutations in this gene can lead to isovaleric acidemia, a metabolic disorder that causes toxic buildup of isovaleric acid and neurological damage.

Overview

The IVD gene provides instructions for making an enzyme called isovaleryl‑CoA dehydrogenase. This enzyme plays an essential role in processing proteins obtained from the diet. 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. In cells throughout the body, isovaleryl‑CoA dehydrogenase is found within specialized structures called mitochondria. Mitochondria convert energy from food to a form that cells can use.

Isovaleryl‑CoA dehydrogenase helps process a particular amino acid called leucine. Specifically, this enzyme is responsible for the third step in the breakdown of leucine. This step is a chemical reaction that converts a molecule called isovaleryl‑CoA to another molecule, 3‑methylcrotonyl‑CoA. Additional chemical reactions convert 3‑methylcrotonyl‑CoA into molecules that are used for energy.

Health Conditions Related to Genetic Changes

Isovaleric acidemia

Nearly 100 mutations in the IVD gene have been identified in people with isovaleric acidemia. Some of these mutations disrupt the normal function of the enzyme, while other mutations prevent the cell from producing any functional enzyme. As a result, the body is unable to break down leucine properly. Defects in leucine processing allow several potentially harmful substances, including a compound called isovaleric acid, to build up to toxic levels in the body. An accumulation of isovaleric acid causes people with isovaleric acidemia to have a characteristic odor of sweaty feet. The buildup of isovaleric acid and related compounds also damages the brain and nervous system, leading to poor feeding, lack of energy (lethargy), seizures, and the other signs and symptoms of isovaleric acidemia.

Idiopathic pulmonary fibrosis

MedlinePlus Genetics provides information about Idiopathic pulmonary fibrosis.

Other Names for This Gene

ACAD2
isovaleryl CoA dehydrogenase
IVD_HUMAN

Additional Information & Resources

Tests Listed in the Genetic Testing Registry

Tests of IVD

Scientific Articles on PubMed

PubMed

Catalog of Genes and Diseases from OMIM

ISOVALERYL-CoA DEHYDROGENASE; IVD

Gene and Variant Databases

NCBI Gene
ClinVar

References

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
Ensenauer R, Vockley J, Willard JM, Huey JC, Sass JO, Edland SD, Burton BK, Berry SA, Santer R, Grunert S, Koch HG, Marquardt I, Rinaldo P, Hahn S, Matern D. A common mutation is associated with a mild, potentially asymptomatic phenotype in patients with isovaleric acidemia diagnosed by newborn screening. Am J Hum Genet. 2004 Dec;75(6):1136-42. doi: 10.1086/426318. Epub 2004 Oct 14. Citation on PubMed or Free article on PubMed Central
Lin WD, Wang CH, Lee CC, Lai CC, Tsai Y, Tsai FJ. Genetic mutation profile of isovaleric acidemia patients in Taiwan. Mol Genet Metab. 2007 Feb;90(2):134-9. doi: 10.1016/j.ymgme.2006.08.011. Epub 2006 Oct 4. Citation on PubMed
Mohsen AW, Anderson BD, Volchenboum SL, Battaile KP, Tiffany K, Roberts D, Kim JJ, Vockley J. Characterization of molecular defects in isovaleryl-CoA dehydrogenase in patients with isovaleric acidemia. Biochemistry. 1998 Jul 14;37(28):10325-35. doi: 10.1021/bi973096r. Citation on PubMed
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
Vockley J, Rogan PK, Anderson BD, Willard J, Seelan RS, Smith DI, Liu W. Exon skipping in IVD RNA processing in isovaleric acidemia caused by point mutations in the coding region of the IVD gene. Am J Hum Genet. 2000 Feb;66(2):356-67. doi: 10.1086/302751. Citation on PubMed or Free article on PubMed Central

Genomic Location

The IVD gene is found on chromosome 15.