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Isovaleric acidemia
Classification & external resources

Isovaleric acid
ICD-10	E71.1
ICD-9	270.3
OMIM	243500
DiseasesDB	29840

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 genetic metabolic disorder Maple syrup urine disease.

Contents 1 Symptoms 2 Genetics 3 References 4 See also 5 External links

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.

The urine of newborn can be screened with mass spectrometry for isovaleric acid, allowing for presymptomatic diagnosis.

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 enzyme encoded by IVD, isovaleric acid-CoA dehydrogenase (EC 1.3.99.10), 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.

• 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

• Methylmalonic acidemia
• Propionic acidemia

• Organic Acidemia Association
• Overview of condition, Genetics Home Reference at NLM
• GPnotebook -187695062

v • d • e Metabolic pathology (E70-90)
Amino acid	Phenylketonuria - Alkaptonuria - Ochronosis - Tyrosinemia - Maple syrup urine disease - Propionic acidemia - Methylmalonic acidemia - Isovaleric acidemia - Primary carnitine deficiency - Cystinuria - Cystinosis - Hartnup disease - Homocystinuria - Citrullinemia - Hyperammonemia - Glutaric acidemia type 1
Carbohydrate	Lactose intolerance - Glycogen storage disease (type I, type II, type III, type IV, type V, type VI), Fructose intolerance, Galactosemia
Lipid	Lipid storage disorders Sphingolipidoses: Gangliosidosis - GM2 gangliosidoses (Sandhoff disease, Tay-Sachs disease) - GM1 gangliosidoses - Mucolipidosis type IV - Gaucher's disease - Niemann-Pick disease - Farber disease - Fabry's disease - Metachromatic leukodystrophy - Krabbe disease Neuronal ceroid lipofuscinosis (Batten disease) - Cerebrotendineous xanthomatosis - Cholesteryl ester storage disease (Wolman disease) Hyperlipidemia - Hypercholesterolemia - Familial hypercholesterolemia - Xanthoma - Combined hyperlipidemia - Lecithin cholesterol acyltransferase deficiency - Tangier disease - Abetalipoproteinemia
Mineral	Cu Wilson's disease/Menkes disease - Fe Haemochromatosis - Zn Acrodermatitis enteropathica - PO43− Hypophosphatemia/Hypophosphatasia - Mg2+ Hypermagnesemia/Hypomagnesemia - Ca2+ Hypercalcaemia/Hypocalcaemia/Disorders of calcium metabolism
Fluid, electrolyte and acid-base balance	Electrolyte disturbance - Na+ Hypernatremia/Hyponatremia - Acidosis (Metabolic, Respiratory, Lactic) - Alkalosis (Metabolic, Respiratory) - Mixed disorder of acid-base balance - H2O Dehydration/Hypervolemia - K+ Hypokalemia/Hyperkalemia - Cl− Hyperchloremia/Hypochloremia
Porphyrin and bilirubin	Acatalasia - Gilbert's syndrome - Crigler-Najjar syndrome - Dubin-Johnson syndrome - Rotor syndrome - Porphyria (Acute intermittent porphyria, Gunther's disease, Porphyria cutanea tarda, Erythropoietic protoporphyria, Hepatoerythropoietic porphyria, Hereditary coproporphyria, Variegate porphyria)
Glycosaminoglycan	Mucopolysaccharidosis - Hurler syndrome - Hunter syndrome - Sanfilippo syndrome - Morquio syndrome
Glycoprotein	I-cell disease - Pseudo-Hurler polydystrophy - Aspartylglucosaminuria - Fucosidosis - Alpha-mannosidosis - Sialidosis
Other	Alpha 1-antitrypsin deficiency - Cystic fibrosis - Familial Mediterranean fever - Lesch-Nyhan syndrome