Isobutyryl-CoA Dehydrogenase Deficiency
Overview
Deficiency of isobutyryl-CoA dehydrogenase causes inability to break down the amino acid valine in protein and results in accumulation of organic acids. The disorder is very rare and the long-term consequences of this condition are unclear, even though infants identified by newborn screening seem to have a very benign course. Historical cases were reported to have cardiomyopathy and carnitine deficiency.Incidence
Rare. Fewer than 5 cases have been published [Isobutyryl-CoA Dehydrogenase Deficiency - Information for Professionals (STAR-G)], although this condition is now routinely identified by newborn screening and cases are no longer published.Prenatal Testing
DNA testing or enzyme analysis by amniocentesis or CVS. Not usually performed given the benign nature of this condition.Clinical Characteristics
With treatment, improvement in growth and normal development can be expected. Treatment consists in carnitine supplementation to prevent deficiency. Without treatment, outcomes are unknown because of the very few observed cases. Symptoms were reported to start at one year of age and may be triggered by fasting and illness. Most patients identified by newborn screening have remained completely asymptomatic.Follow-up Testing after Positive Screen
Quantitative plasma acylcarnitine profile, urine organic acids, urine acylglycinesPrimary Care Management
Upon Notification of the + Screen
- Contact the family and evaluate the infant for any symptom.
- There is no need for emergency protocols for this condition.
- To confirm the diagnosis, work with the following service(s): Newborn Screening Services (see NW providers [2]).
- For evaluation and ongoing collaborative management, consult the following service(s): Pediatric Genetics (see NW providers [1]).
If the Diagnosis is Confirmed
- Educate the family regarding signs, symptoms, and the need for urgent care when the infant becomes ill(see Isobutyryl-CoA Dehydrogenase Deficiency - Information for Parents (STAR-G) for additional information).
- No special diet is necessary for this condition.
- Oral L-carnitine may be indicated.
- 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
Isobutyryl-CoA Dehydrogenase Deficiency (OMIM)
Extensive review of literature that provides technical information on genetic disorders; Online Mendelian Inheritance in Man
site, hosted by Johns Hopkins University.
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.
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
Isobutyryl-CoA Dehydrogenase Deficiency (Genetics Home Reference)
Excellent, detailed review of condition for patients and families; sponsored by the U.S. National Library of Medicine.
Isobutyryl-CoA Dehydrogenase Deficiency - 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 this newborn disorder; Screening, Technology and Research in Genetics.
Baby's First Test: Isobutyryl-CoA Dehydrogenase Deficiency (Genetic Alliance)
Information about early signs, follow-up testing, treatment, accessing care, and expected outcomes. Provides links to support
services.
National Newborn Screening and Global Resource Center (NNSGRC)
Provides information about each state's newborn screening programs; sponsored by the University of Texas Health Science Center
at San Antonio, Department of Pediatrics.
Tools
ACT Sheet for Elevated C4 Acylcarnitine (ACMG) (
349 KB)
Contains short-term recommendations for clinical follow-up of the newborn who has screened positive; American College of Medical
Genetics.
Confirmatory Algorithm for Elevated C4 Acylcarnitine (ACMG) ()
Contains short-term recommendations for clinical follow-up of the newborn who has screened positive; American College of Medical
Genetics.
Services Nationwide
Newborn Screening Services
See all Newborn Screening Services services providers (2) in our database.
For other services related to this condition, browse our Services categories or search our database.
Helpful Articles
PubMed search for isobutyryl-CoA dehydrogenase deficiency.
Pasquali M, Monsen G, Richardson L, Alston M, Longo N.
Biochemical findings in common inborn errors of metabolism.
Am J Med Genet C Semin Med Genet.
2006;142C(2):64-76.
PubMed abstract
Santra S, Macdonald A, Preece MA, Olsen RK, Andresen BS.
Long-term outcome of isobutyryl-CoA dehydrogenase deficiency diagnosed following an episode of ketotic hypoglycaemia.
Mol Genet Metab Rep.
2017;10:28-30.
PubMed abstract / Full Text
Yun JW, Jo KI, Woo HI, Lee SY, Ki CS, Kim JW, Song J, Lee DH, Lee YW, Park HD.
A novel ACAD8 mutation in asymptomatic patients with isobutyryl-CoA dehydrogenase deficiency and a review of the ACAD8 mutation
spectrum.
Clin Genet.
2015;87(2):196-8.
PubMed abstract