Isovaleric acidemia

Disorder Category

An organic acidemia



Elevated C5 (isovaleryl carnitine)

Tested By

Tandem mass spectrometry (MS/MS); sensitivity=NA; specificity=NA


Isovaleric acidemia

Isovaleric acid-CoA dehydrogenase deficiency

Isovaleryl-CoA dehydrogenase deficiency


IVD deficiency


270.3, disturbances of branched-chain amino-acid metabolism

E71.110, isovaleric acidemia


Lack of isovaleryl-CoA dehydrogenase, which is involved in the metabolism of the branched chain amino acid leucine, results in the inability to break down isovaleric acid and the accumulation of potentially toxic metabolites. Clinical manifestations of the illness include an acute neonatal form, a chronic intermittent form, and a very mild form of unknown clinical significance.


Incidence in the United States is approximately 1:159,000. [Therrell: 2014]


Autosomal recessive

Maternal & Family History

In most cases, there is no previous family history of this condition. Children develop normally during pregnancy. Mothers with isovaleric acidemia have had normal children.

Prenatal Testing

DNA testing or enzyme analysis by amniocentesis or CVS

Clinical Characteristics

With early diagnosis and ongoing treatment, most affected children will have normal development. Without treatment, children with the chronic, intermittent form may suffer neurologic damage, though most children are developmentally normal. Those children with the acute neonatal form will present in the first few days or weeks of life and about half will die during their first episode. In many cases, the neonatal presentation occurs before the return of newborn screening results. After the neonatal period, symptoms may be triggered by consuming too much protein, and illness. Children may be healthy between metabolic crisis episodes.

Initial symptoms may include:
  • A "sweaty feet" odor
  • Vomiting
  • Lethargy progressing to coma
  • Lab findings:
    • Ketoacidosis
    • Elevated ammonia levels in the blood
    • Neutropenia, thrombocytopenia, anemia

Follow-up Testing after Positive Screen

Quantitative plasma acylcarnitine profile, urine organic acids, and urine acylglycine analysis

Primary Care Management

Upon Notification of the + Screen

  • Contact the family and evaluate the infant for poor feeding, vomiting, lethargy, and odor of sweaty feet.
  • Provide emergency treatment and referral for symptoms of poor feeding or vomiting.
  • Continue breastfeeding if the infant appears healthy. If not, the child should be admitted to the hospital for treatment (breast milk contains fewer proteins than regular formulas).
  • If in doubt, obtain BMP to check CO2 and anion gap and urine analysis (for ketones).
  • Confirm the diagnosis and work with the following service(s): see all Newborn Screening Programs services providers (3) in our database.
  • Evaluate and continue ongoing collaborative management, consult the following service(s): Pediatric Medical Genetics , (801-213-3599); See also Services below.

If the Diagnosis is Confirmed

  • Educate the family about signs, symptoms, and the need for urgent care if the infant becomes ill. (See Isovaleric Acidemia - Information for Parents (STAR-G) for additional information.)
  • Consider low protein, low leucine, and high carbohydrate meals for affected children.
  • Most patients require oral L-carnitine and glycine for some affected children.
  • Patients need intravenous calories (glucose, intralipids) and bicarbonate during metabolic crisis episodes.
  • Evaluate and continue ongoing collaborative management; consult the following service(s): Pediatric Medical Genetics , (801-213-3599); See also Services below.

Specialty Care Collaboration

Provide initial consultation and ongoing collaboration, particularly for dietary management. Facilitate genetic counseling for the family.


Information & Support

For Professionals

Isovaleric Acidemia - Information for Professionals (STAR-G)
Structured list of information about the condition and links to more information; Screening, Technology, and Research in Genetics.

ACT Sheet for Isovaleric Acidemia (ACMG) (PDF Document 275 KB)
Contains short-term recommendations for clinical follow-up of the newborn who has screened positive; American College of Medical Genetics.

Confirmatory Algorithm for Isovaleric Acidemia (ACMG) (PDF Document 90 KB)
Resource for clinicians to help confirm diagnosis; American College of Medical Genetics.

Isovaleric Acidemia Acute Illness Protocol (NECMP)
A guideline for health care professionals treating the sick infant/child who has previously been diagnosed with isovaleric acidemia; developed under the direction of Dr. Harvey Levy, Senior Associate in Medicine/Genetics at Children’s Hospital Boston, and Professor of Pediatrics at Harvard Medical School, for the New England Consortium of Metabolic Programs.

Isovaleric Acidemia (OMIM)
Extensive review of the literature, including clinical features and gene therapy; Online Mendelian Inheritance in Man, hosted by Johns Hopkins University.

Genetics in Primary Care Institute (AAP)
The goal of this site is to increase collaboration in the care of children with known or suspected genetic disorders. Includes health supervision guidelines and other useful resources; a collaboration among the Health Resources & Services Administration, the Maternal and Child Health Bureau, and the American Academy of Pediatrics.

Utah Newborn Screening Program (UDOH)
Provides information about the program, related legislation, training for practices, and newborn conditions; Utah Department of Health.

For Parents and Patients


Organic Acidemia Association (OAA)
A nonprofit organization that provides information, newsletters, calendars of events, connections with other parents, a listserv, a discussion board, and nutrition and recipe ideas.


Isovaleric Acidemia - Information for Parents (STAR-G)
A fact sheet, written by a genetic counselor and reviewed by metabolic and genetic specialists, for families who have received an initial diagnosis of a newborn disorder; Screening, Technology and Research in Genetics.

Isovaleric Acidemia (Genetics Home Reference)
Excellent, detailed review of condition for patients and families; sponsored by the U.S. National Library of Medicine.

Isovaleric Acidemia: A Guide for Parents (PacNoRGG) (PDF Document 1.4 MB)
Eight-page guide that includes an overview, social concerns, sample treatment plan, glossary, regional resources, and references; sponsored by the Pacific Northwest Regional Genetics Group.

Isovaleric Acidemia: A Guide for Parents (PacNoRGG) (Spanish) (PDF Document 187 KB)
Spanish translation of an 8-page guide that includes an overview, social concerns, sample treatment plan, glossary, regional resources, and references; sponsored by the Pacific Northwest Regional Genetics Group.

Newborn Screening Information for Clinicians (NNSGRC)
Fact sheets, data reports, publications ,and information for clinicians about genetic screening that includes links to state genetic contacts; National Newborn Screening & Global Resource Center.


Genetics-related clinical services throughout the world can be found through Genetics Clinic Directory (GeneTests).

Newborn Screening Programs

See all Newborn Screening Programs services providers (3) in our database.

Pediatric Genetics

See all Pediatric Genetics services providers (5) in our database.

For other services related to this condition, browse our Services categories or search our database.

Helpful Articles

PubMed search for isovaleric acidemia, last 5 years.

Vockley J, Ensenauer R.
Isovaleric acidemia: new aspects of genetic and phenotypic heterogeneity.
Am J Med Genet C Semin Med Genet. 2006;142C(2):95-103. PubMed abstract / Full Text


Author: Nicola Longo, MD, PhD - 12/2015
Content Last Updated: 12/2015

Page Bibliography

Therrell BL Jr, Lloyd-Puryear MA, Camp KM, Mann MY.
Inborn errors of metabolism identified via newborn screening: Ten-year incidence data and costs of nutritional interventions for research agenda planning.
Mol Genet Metab. 2014;113(1-2):14-26. PubMed abstract / Full Text