Isovaleric Acidemia
Other Names
Isovaleric acid-CoA dehydrogenase deficiency
Isovaleryl-CoA dehydrogenase deficiency
IVA
IVD deficiency
Overview
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
Incidence in the United States is approximately 1:159,000 [Therrell: 2014]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.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 analysisPrimary 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): Newborn Screening Services (see UT providers [4]).
- Evaluate and continue ongoing collaborative management, consult the following service(s): Pediatric Genetics (see UT providers [6]).
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 Genetics (see UT providers [6]).
Specialty Care Collaboration
Provide initial consultation and ongoing collaboration, particularly for dietary management. Facilitate genetic counseling for the family.Resources
Information & Support
For Professionals
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.
Resources for Isovaleric Acidemia (Disease InfoSearch)
Compilation of information, articles, research, case studies, and genetics links; from Genetic Alliance.
National Newborn Screening & Global Resource Center (NNSGRC)
Fact sheets, data reports, publications, and information for clinicians about genetic screening that includes links to state
genetic contacts.
Genetics in Primary Care Institute (AAP)
Contains health supervision guidelines and other useful resources for the care of children with genetic disorders; 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
Support
Organic Acidemia Association (OAA)
A nonprofit organization that provides information, support, events, connections with other parents, a discussion board,
and nutrition and recipe ideas.
General
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) (
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) ( 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.
Tools
ACT Sheet for Isovaleric Acidemia (ACMG) ()
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) ( 90 KB)
Resource for clinicians to help confirm diagnosis; American College of Medical Genetics.
Services in Utah
Newborn Screening Services
See all Newborn Screening Services services providers (4) 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
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