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Genetics Home Reference: your guide to understanding genetic conditions     A service of the U.S. National Library of Medicine®

2-methylbutyryl-CoA dehydrogenase deficiency

Reviewed April 2007

What is 2-methylbutyryl-CoA dehydrogenase deficiency?

2-methylbutyryl-CoA dehydrogenase deficiency is a type of organic acid disorder in which the body is unable to process proteins properly. Organic acid disorders lead to an abnormal buildup of particular acids known as organic acids. Abnormal levels of organic acids in the blood (organic acidemia), urine (organic aciduria), and tissues can be toxic and can cause serious health problems.

Normally, the body breaks down proteins from food into smaller parts called amino acids. Amino acids can be further processed to provide energy for growth and development. People with 2-methylbutyryl-CoA dehydrogenase deficiency have inadequate levels of an enzyme that helps process a particular amino acid called isoleucine.

Health problems related to 2-methylbutyryl-CoA dehydrogenase deficiency vary widely from severe and life-threatening to mild or absent. Signs and symptoms of this disorder can begin a few days after birth or later in childhood. The initial symptoms often include poor feeding, lack of energy (lethargy), vomiting, and an irritable mood. These symptoms sometimes progress to serious medical problems such as difficulty breathing, seizures, and coma. Additional problems can include poor growth, vision problems, learning disabilities, muscle weakness, and delays in motor skills such as standing and walking.

Symptoms of 2-methylbutyryl-CoA dehydrogenase deficiency may be triggered by prolonged periods without food (fasting), infections, or eating an increased amount of protein-rich foods. Some people with this disorder never have any signs or symptoms (asymptomatic). For example, individuals of Hmong ancestry identified with 2-methylbutyryl-CoA dehydrogenase deficiency through newborn screening are usually asymptomatic.

How common is 2-methylbutyryl-CoA dehydrogenase deficiency?

2-methylbutyryl-CoA dehydrogenase deficiency is a rare disorder; its actual incidence is unknown. This disorder is more common, however, among Hmong populations in southeast Asia and in Hmong Americans. 2-methylbutyryl-CoA dehydrogenase deficiency occurs in 1 in 250 to 1 in 500 people of Hmong ancestry.

What genes are related to 2-methylbutyryl-CoA dehydrogenase deficiency?

Mutations in the ACADSB gene cause 2-methylbutyryl-CoA dehydrogenase deficiency.

The ACADSB gene provides instructions for making an enzyme called 2-methylbutyryl-CoA dehydrogenase that helps process the amino acid isoleucine. Mutations in the ACADSB gene reduce or eliminate the activity of this enzyme. With a shortage (deficiency) of 2-methylbutyryl-CoA dehydrogenase, the body is unable to break down isoleucine properly. As a result, isoleucine is not converted to energy, which can lead to characteristic features of this disorder, such as lethargy and muscle weakness. Also, an organic acid called 2-methylbutyrylglycine and related compounds may build up to harmful levels, causing serious health problems.

Related Gene(s)

Changes in this gene are associated with 2-methylbutyryl-CoA dehydrogenase deficiency.


How do people inherit 2-methylbutyryl-CoA dehydrogenase deficiency?

This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.

Where can I find information about diagnosis or management of 2-methylbutyryl-CoA dehydrogenase deficiency?

These resources address the diagnosis or management of 2-methylbutyryl-CoA dehydrogenase deficiency and may include treatment providers.

  • Baby's First Test (
  • Gene Review: Organic Acidemias Overview (
  • Genetic Testing Registry: Deficiency of 2-methylbutyryl-CoA dehydrogenase (

You might also find information on the diagnosis or management of 2-methylbutyryl-CoA dehydrogenase deficiency in Educational resources and Patient support.

General information about the diagnosis ( and management ( of genetic conditions is available in the Handbook. Read more about genetic testing (, particularly the difference between clinical tests and research tests (

To locate a healthcare provider, see How can I find a genetics professional in my area? ( in the Handbook.

Where can I find additional information about 2-methylbutyryl-CoA dehydrogenase deficiency?

You may find the following resources about 2-methylbutyryl-CoA dehydrogenase deficiency helpful. These materials are written for the general public.

You may also be interested in these resources, which are designed for healthcare professionals and researchers.

What other names do people use for 2-methylbutyryl-CoA dehydrogenase deficiency?

  • 2-MBADD
  • 2-MBCD deficiency
  • 2-MBG
  • 2-methylbutyryl-coenzyme A dehydrogenase deficiency
  • 2-methylbutyryl glycinuria
  • short/branched-chain acyl-CoA dehydrogenase deficiency

For more information about naming genetic conditions, see the Genetics Home Reference Condition Naming Guidelines ( and How are genetic conditions and genes named? ( in the Handbook.

What if I still have specific questions about 2-methylbutyryl-CoA dehydrogenase deficiency?

Ask the Genetic and Rare Diseases Information Center (

What glossary definitions help with understanding 2-methylbutyryl-CoA dehydrogenase deficiency?

acids ; aciduria ; amino acid ; asymptomatic ; autosomal ; autosomal recessive ; cell ; CoA ; coenzyme A ; coma ; deficiency ; dehydrogenase ; disabilities ; enzyme ; fasting ; gene ; incidence ; inherited ; isoleucine ; lethargy ; motor ; newborn screening ; organic acid ; protein ; recessive ; screening ; toxic

You may find definitions for these and many other terms in the Genetics Home Reference Glossary.


  • Andresen BS, Christensen E, Corydon TJ, Bross P, Pilgaard B, Wanders RJ, Ruiter JP, Simonsen H, Winter V, Knudsen I, Schroeder LD, Gregersen N, Skovby F. Isolated 2-methylbutyrylglycinuria caused by short/branched-chain acyl-CoA dehydrogenase deficiency: identification of a new enzyme defect, resolution of its molecular basis, and evidence for distinct acyl-CoA dehydrogenases in isoleucine and valine metabolism. Am J Hum Genet. 2000 Nov;67(5):1095-103. Epub 2000 Sep 29. (
  • Korman SH. Inborn errors of isoleucine degradation: a review. Mol Genet Metab. 2006 Dec;89(4):289-99. Epub 2006 Sep 6. Review. (
  • Madsen PP, Kibaek M, Roca X, Sachidanandam R, Krainer AR, Christensen E, Steiner RD, Gibson KM, Corydon TJ, Knudsen I, Wanders RJ, Ruiter JP, Gregersen N, Andresen BS. Short/branched-chain acyl-CoA dehydrogenase deficiency due to an IVS3+3A>G mutation that causes exon skipping. Hum Genet. 2006 Feb;118(6):680-90. Epub 2005 Nov 30. (
  • Matern D, He M, Berry SA, Rinaldo P, Whitley CB, Madsen PP, van Calcar SC, Lussky RC, Andresen BS, Wolff JA, Vockley J. Prospective diagnosis of 2-methylbutyryl-CoA dehydrogenase deficiency in the Hmong population by newborn screening using tandem mass spectrometry. Pediatrics. 2003 Jul;112(1 Pt 1):74-8. Review. (
  • 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 May 15;142C(2):64-76. Review. (


The resources on this site should not be used as a substitute for professional medical care or advice. Users seeking information about a personal genetic disease, syndrome, or condition should consult with a qualified healthcare professional. See How can I find a genetics professional in my area? ( in the Handbook.

Reviewed: April 2007
Published: February 8, 2016