Isobutyryl-CoA dehydrogenase (IBD) deficiency is a condition that disrupts the breakdown of certain proteins. Normally, proteins from food are broken down into amino acids. Amino acids can be further processed to provide energy for growth and development. People with IBD deficiency have problems breaking down the amino acid valine.

Most people with IBD deficiency are asymptomatic, which means that they do not have any signs or symptoms of the condition. If signs or symptoms do appear, they typically show early in life and only last for a short period of time. These signs and symptoms can include weak muscle tone (hypotonia), developmental delays, slow growth, a low number of red blood cells (anemia), and seizures. Because IBD deficiency is rare and often does not cause signs and symptoms, it is difficult to know if the health problems seen in affected individuals are caused by this condition or if those health problems are unrelated to the condition. It is also unclear whether IBD deficiency causes health problems later in life.

Newborn screening, which identifies abnormal levels of certain compounds in the blood, can detect IBD deficiency. People with IBD deficiency have high levels of a compound called carnitine (specifically a form called C4-acylcarnitine). Cells use carnitine, a natural substance that is acquired mostly through the diet, to process fats and produce energy.

IBD deficiency is a rare disorder. Worldwide, the prevalence of this disorder is estimated to vary from 1 in 52,000 to 292,000 people.

Variants (also called mutations) in the ACAD8 gene cause IBD deficiency. This gene provides instructions for making the IBD enzyme. This enzyme is found in mitochondria, which are the energy producing centers inside cells. Within mitochondria, the IBD enzyme is involved in breaking down valine. Specifically, this enzyme functions in the third step of this process, which converts the molecule isobutyryl-CoA to the molecule methacrylyl-CoA. This is a critical step in the process of converting the energy from food into a form that cells can use.

ACAD8 gene variants reduce or eliminate the activity of the IBD enzyme. As a result, valine cannot be broken down properly. This may lead to reduced energy production and cause the features of IBD deficiency in some people.

Genetic Testing Information

• Genetic Testing Registry: Deficiency of isobutyryl-CoA dehydrogenase

Genetic and Rare Diseases Information Center

• Isobutyryl-CoA dehydrogenase deficiency

Patient Support and Advocacy Resources

• National Organization for Rare Disorders (NORD)

Clinical Trials

• ClinicalTrials.gov

Catalog of Genes and Diseases from OMIM

• ISOBUTYRYL-CoA DEHYDROGENASE DEFICIENCY; IBDD

Scientific Articles on PubMed

• PubMed

• Feng J, Yang C, Zhu L, Zhang Y, Zhao X, Chen C, Chen QX, Shu Q, Jiang P, Tong F. Phenotype, genotype and long-term prognosis of 40 Chinese patients with isobutyryl-CoA dehydrogenase deficiency and a review of variant spectra in ACAD8. Orphanet J Rare Dis. 2021 Sep 20;16(1):392. doi: 10.1186/s13023-021-02018-6. Erratum In: Orphanet J Rare Dis. 2021 Dec 7;16(1):505. doi: 10.1186/s13023-021-02132-5. Citation on PubMed
• Koeberl DD, Young SP, Gregersen NS, Vockley J, Smith WE, Benjamin DK Jr, An Y, Weavil SD, Chaing SH, Bali D, McDonald MT, Kishnani PS, Chen YT, Millington DS. Rare disorders of metabolism with elevated butyryl- and isobutyryl-carnitine detected by tandem mass spectrometry newborn screening. Pediatr Res. 2003 Aug;54(2):219-23. doi: 10.1203/01.PDR.0000074972.36356.89. Epub 2003 May 7. Citation on PubMed
• Lin Y, Peng W, Jiang M, Lin C, Lin W, Zheng Z, Li M, Fu Q. Clinical, biochemical and genetic analysis of Chinese patients with isobutyryl-CoA dehydrogenase deficiency. Clin Chim Acta. 2018 Dec;487:133-138. doi: 10.1016/j.cca.2018.09.033. Epub 2018 Sep 22. Citation on PubMed
• Nguyen TV, Andresen BS, Corydon TJ, Ghisla S, Abd-El Razik N, Mohsen AW, Cederbaum SD, Roe DS, Roe CR, Lench NJ, Vockley J. Identification of isobutyryl-CoA dehydrogenase and its deficiency in humans. Mol Genet Metab. 2002 Sep-Oct;77(1-2):68-79. doi: 10.1016/s1096-7192(02)00152-x. Citation on PubMed
• Oglesbee D, He M, Majumder N, Vockley J, Ahmad A, Angle B, Burton B, Charrow J, Ensenauer R, Ficicioglu CH, Keppen LD, Marsden D, Tortorelli S, Hahn SH, Matern D. Development of a newborn screening follow-up algorithm for the diagnosis of isobutyryl-CoA dehydrogenase deficiency. Genet Med. 2007 Feb;9(2):108-16. doi: 10.1097/gim.0b013e31802f78d6. Citation on PubMed
• Pedersen CB, Bischoff C, Christensen E, Simonsen H, Lund AM, Young SP, Koeberl DD, Millington DS, Roe CR, Roe DS, Wanders RJ, Ruiter JP, Keppen LD, Stein Q, Knudsen I, Gregersen N, Andresen BS. Variations in IBD (ACAD8) in children with elevated C4-carnitine detected by tandem mass spectrometry newborn screening. Pediatr Res. 2006 Sep;60(3):315-20. doi: 10.1203/01.pdr.0000233085.72522.04. Epub 2006 Jul 20. Citation on PubMed
• Roe CR, Cederbaum SD, Roe DS, Mardach R, Galindo A, Sweetman L. Isolated isobutyryl-CoA dehydrogenase deficiency: an unrecognized defect in human valine metabolism. Mol Genet Metab. 1998 Dec;65(4):264-71. doi: 10.1006/mgme.1998.2758. Citation on PubMed
• Yoo EH, Cho HJ, Ki CS, Lee SY. Isobutyryl-CoA dehydrogenase deficiency with a novel ACAD8 gene mutation detected by tandem mass spectrometry newborn screening. Clin Chem Lab Med. 2007;45(11):1495-7. doi: 10.1515/CCLM.2007.317. Citation on PubMed
• Zhang Z, Sun Y, Wang YY, Ma DY, Wang X, Cheng W, Jiang T. Retrospective analysis of isobutyryl CoA dehydrogenase deficiency. Minerva Pediatr (Torino). 2024 Oct;76(5):645-651. doi: 10.23736/S2724-5276.21.06179-6. Epub 2021 Oct 14. Citation on PubMed