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Isobutyryl-CoA Dehydrogenase Deficiency

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Guidance for primary care clinicians receiving a positive newborn screen result

Other Names

ACAD 8 Deficiency
IBD Deficiency
IBDH
Isobutyrylglycinuria (IBG)

ICD-10 Coding

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

Disorder Category

Organic acidemia

Screening

Abnormal Finding

Elevated C4 (butyrylcarnitine)

Tested By

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

Description

Isobutyryl-CoA dehydrogenase is involved in the valine degradation pathway. Insufficient enzyme activity results in a particular biochemical pattern with elevated butyrylcarnitine /isobutyrylcarnitine. However, the clinical significance of this has been debated since the majority of those identified by expanded newborn screening have remained asymptomatic and require no treatment.

Clinical Characteristics

Isobutyryl-CoA dehydrogenase deficiency is considered by most to be a benign biochemical phenotype and therefore is not expected to cause clinical symptoms. The first case of the condition was reported to have anemia and dilated cardiomyopathy, although this may have been a coincidence. Some cases have since been reported to have mild speech delays or poor growth but not at a level statistically greater than in the general population.

Incidence

The incidence of isobutyryl-CoA dehydrogenase deficiency is not known due to its rarity.

Inheritance

Autosomal recessive

Primary Care Management

Next Steps After a Positive Screen

  • Contact the family and evaluate the infant for any symptoms.
  • There is no need for emergency protocols for this condition.

Confirming the Diagnosis

  • To confirm the diagnosis of isobutyryl-CoA dehydrogenase deficiency, work with Newborn Screening Services (see NW providers [1]). Confirmation is necessary given the differential diagnosis for an elevated C4 level that includes short-chain acyl-CoA dehydrogenase (SCAD) deficiency and ethylmalonic acidemia.
  • Follow-up testing will include quantitative plasma acylcarnitine profile, urine organic acids, and urine acylglycines.

If the Diagnosis is Confirmed

Resources

Information & Support

For Professionals

Isobutyryl-CoA Dehydrogenase Deficiency (OMIM)
Information about clinical features, diagnosis, management, and molecular and population genetics; Online Mendelian Inheritance in Man, authored and edited at the McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University School of Medicine

For Parents and Patients

Isobutyryl-CoA Dehydrogenase Deficiency (MedlinePlus)
Information for families that includes description, frequency, causes, inheritance, other names, and additional resources; from the 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.

Tools

ACT Sheet for Elevated C4 Acylcarnitine (ACMG) (PDF Document 349 KB)
Provides recommendations for clinical and laboratory follow-up of the newborn with out-of-range screening results, along with national resources for clinicians and families; American College of Medical Genetics.

Confirmatory Algorithm for SCADD/Elevated C4 (ACMG) (PDF Document 202 KB)
Contains short-term recommendations for clinical follow-up of the newborn who has screened positive; American College of Medical Genetics.

Services for Patients & Families Nationwide (NW)

For services not listed above, browse our Services categories or search our database.

* number of provider listings may vary by how states categorize services, whether providers are listed by organization or individual, how services are organized in the state, and other factors; Nationwide (NW) providers are generally limited to web-based services, provider locator services, and organizations that serve children from across the nation.

Helpful Articles

PubMed search for isobutyryl-CoA dehydrogenase deficiency.

Sadat R, Hall PL, Wittenauer AL, Vengoechea ED, Park K, Hagar AF, Singh R, Moore RH, Gambello MJ.
Increased parental anxiety and a benign clinical course: Infants identified with short-chain acyl-CoA dehydrogenase deficiency and isobutyryl-CoA dehydrogenase deficiency through newborn screening in Georgia.
Mol Genet Metab. 2020;129(1):20-25. 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: March 2007; last update/revision: August 2023
Current Authors and Reviewers:
Authors: Kimberly Stowers, MD
Hannah Holik, MD
Senior Author: Brian J. Shayota, MD, MPH
Authoring history
2018: update: Nicola Longo, MD, Ph.D.A
2011: first version: Nicola Longo, MD, Ph.D.A
AAuthor; CAContributing Author; SASenior Author; RReviewer

Page Bibliography

Sadat R, Hall PL, Wittenauer AL, Vengoechea ED, Park K, Hagar AF, Singh R, Moore RH, Gambello MJ.
Increased parental anxiety and a benign clinical course: Infants identified with short-chain acyl-CoA dehydrogenase deficiency and isobutyryl-CoA dehydrogenase deficiency through newborn screening in Georgia.
Mol Genet Metab. 2020;129(1):20-25. 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