Isobutyryl-CoA Dehydrogenase Deficiency

Other Names

Acyl-CoA dehydrogenase family, member 8

IBDH

Isobutyrylglycinuria (IBG)

Diagnosis Coding

E71.19, Other disorders of branched-chain amino-acid metabolism

Disorder Category

An organic acidemia

Screening

Finding

Elevated C4 (butyrylcarnitine)

Tested By

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

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.

Inheritance

Autosomal recessive

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 acylglycines

Primary Care Management

Upon Notification of the + Screen

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.

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) (PDF Document 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)
Resource for clinicians to help confirm diagnosis; American College of Medical Genetics.

Services in Montana

Select services for a different state: ID, NM, NV, RI, UT
Genetics clinic services throughout the US can be found through the Genetics Clinic Services Search Engine (ACMG).

Newborn Screening Programs

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

Pediatric Genetics

See all Pediatric Genetics services providers (6) 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

Authors & Reviewers

Initial Publication: December 2007; Last Update: July 2018
Current Authors and Reviewers (click on name for bio):
Author: Nicola Longo, MD, Ph.D.
Reviewer: Nicola Longo, MD, Ph.D.