Home > Newborn Disorders > Isovaleric acidemia
Isovaleric acidemia
Overview
Lack of isovaleryl-CoA dehydrogenase, involved in the metabolism of the branched chain amino acid leucine, results in the inability to break down isovaleric acid, resulting in 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.Prevalence
about 1/250,000 live births in the US (1/62,500 in Germany) [Ensenauer: 2004]Clinical Characteristics
With early diagnosis and ongoing treatment, most affected children will have normal development. Without treatment, those with the chronic, intermittent form may suffer neurologic damage, though most are developmentally normal. Those 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. 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:
- "sweaty feet" odor;
- vomiting;
- lethargy progressing to coma;
- lab findings:
- ketoacidosis;
- elevated ammonia levels in the blood; and
- neutropenia, thrombocytopenia, anemia.
Follow-up on positive screening test
Quantitative plasma acylcarnitine profile, urine organic acids, urine acylglycine and acylcarnitine analysis.Primary care management
Upon notification of the + screen
- Contact the family and evaluate the infant for poor feeding, vomiting, lethargy, odor of sweaty feet;
- Provide emergency treatment/referral for symptoms of poor feeding, vomiting;
- Discontinue breast or cow milk formula feeding;
- To confirm the diagnosis, work with the following service(s): Utah Newborn Screening Program, (801-584-8256); See also Services below;
- For evaluation and ongoing collaborative management, consult the following service(s): Medical Genetics, (801-231-3599); See also Services below;
If the diagnosis is confirmed
- Educate the family regarding signs, symptoms, and the need for urgent care when the infant becomes ill (see Isovaleric acidemia info for parents (STAR-G) for additional information);
- Low protein, low leucine, and high carbohydrate meals may be indicated for affected children;
- Oral L-carnitine and glycine may be indicated for some affected children;
- Bicarbonate and glucose may be indicated during metabolic crisis episodes;
- For those identified after irreversible consequences, assist in management, particularly with developmental and educational interventions.
Specialty Care Collaboration
Initial consultation and ongoing collaboration, particularly for dietary management. Genetic counseling for the family.Resources
Information & Support
For Professionals
Isovaleric acidemia info for professionals (STAR-G)
On the Screening, Technology and Research in Genetics (STAR-G) site, one of a series of Disorder Fact Sheets for Professionals;
structured list of information about the condition, with links to more information.
ACT Sheet for elevated C5 Acylcarnitine (ACMG)
(
348 KB)
Developed by the American College of Medical Genetics (ACMG), includes recommended responses to positive newborn screening
test results, diagnostic evaluation, clinical expectations, and sources of additional information. See the ACMG ACT Sheets
and Confirmatory Algorithms (link elsewhere on this page) for more info and sheets on other conditions.
ACT Sheets and Confirmatory Algorithms (ACMG)
The American College of Medical Genetics (ACMG) has developed ACTion (ACT) Sheets and algorithms for responding to positive
newborn screening test results. This page contains a table with links to all of the ACT Sheets and related algorithms.
Isovaleric acidemia Acute Illness Protocol (NECMP)
A guideline for healthcare 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.
Resources for isovaleric acidemia
Comprehensive compilation of links to information, articles, research, case studies, genetics, and more; from the National
Library of Medicine and the Genetic Alliance.
Isovaleric acidemia (OIMM)
From the Online Mendelian Inheritance in Man site, hosted by Johns Hopkins University, providing technical information for
providers on genetic disorders, links to MEDLINE, and links to other scientific information and sites.
For Parents and Patients
Isovaleric acidemia info for parents (STAR-G)
From the Screening, Technology and Research in Genetics (STAR-G) site, providing information for parents about isovaleric
acidemia and links to other sites including parent support groups.
Isovaleric acidemia (Genetics Home Reference)
Excellent, detailed review aimed at patients and families from the National Library of Medicine's Genetics Home Reference
site.
Isovaleric acidemia - A Guide for Parents
( 1.4 MB)
A detailed, 8-page booklet from the Pacific Northwest Regional Genetics Group, including specific dietary guidelines.
Isovaleric acidemia - A Guide for Parents (Spanish)
( 187 KB)
Spanish translation of a detailed, 8-page booklet from the Pacific Northwest Regional Genetics Group, including specific dietary
guidelines.
Organic Acidemia Association (OAA)
A non-profit organization that provides information for parents and providers; newsletters; event information; connections
with other parents; a listserv; a discussion board; information about nutrition and recipes; translation of their web pages
into five other languages; hosting of the Propionic Acidemia Research Network and other research funds; and links to other
sites.
National Newborn Screening & Genetics Resource Center
Provides information for families and professionals about genetic screening; links to support and advocacy groups; links to
state genetic contacts; newsletters; fact sheets; data reports; publications; and more.
Services
Newborn Screening Programs
Utah Newborn Screening Program,
more info...
44 Mario Capecchi Drive
Salt Lake City, UT 84114
Phone: 801-584-8256
Fax: 801-536-0966
http://health.utah.gov/newbornscreening
Pediatric Medical Genetics
See all Pediatric Medical Genetics services providers (3) in our database.
For other services related to this condition, browse our Services categories or search our database.
Helpful Articles
PubMed search for articles on isovaleric acidemia in the 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
Authors
| Author: | Nicola Longo MD, PhD, 3/2007 |
| Compiled and edited by: | Alfred Romeo RN, PhD, 3/2007 |
| Content Last Updated: | 7/2010 |
Page Bibliography
Ensenauer R, Vockley J, Willard JM, Huey JC, Sass JO, Edland SD, Burton BK, Berry SA, Santer R, Grünert 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;75(6):1136-42.
PubMed abstract / Full Text