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Genetics Home Reference: your guide to understanding genetic conditions
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3-methylcrotonyl-CoA carboxylase deficiency

(often shortened to 3-MCC deficiency)
Reviewed October 2008

What is 3-MCC deficiency?

3-methylcrotonyl-CoA carboxylase deficiency (also known as 3-MCC deficiency) is an inherited disorder in which the body is unable to process certain proteins properly. People with this disorder have a shortage of an enzyme that helps break down proteins containing a particular building block (amino acid) called leucine.

Infants with 3-MCC deficiency appear normal at birth but usually develop signs and symptoms in infancy or early childhood. The characteristic features of this condition, which can range from mild to life-threatening, include feeding difficulties, recurrent episodes of vomiting and diarrhea, excessive tiredness (lethargy), and weak muscle tone (hypotonia). If untreated, this disorder can lead to delayed development, seizures, and coma. Many of these complications can be prevented with early detection and lifelong management with a low-protein diet and appropriate supplements. Some people with gene mutations that cause 3-MCC deficiency never experience any signs or symptoms of the condition.

The characteristic features of 3-MCC deficiency are similar to those of Reye syndrome, a severe disorder that develops in children while they appear to be recovering from viral infections such as chicken pox or flu. Most cases of Reye syndrome are associated with the use of aspirin during these viral infections.

How common is 3-MCC deficiency?

This condition is detected in an estimated 1 in 36,000 newborns worldwide.

What genes are related to 3-MCC deficiency?

Mutations in the MCCC1 or MCCC2 gene can cause 3-MCC deficiency. These two genes provide instructions for making different parts (subunits) of an enzyme called 3-methylcrotonyl-coenzyme A carboxylase (3-MCC). This enzyme plays a critical role in breaking down proteins obtained from the diet. Specifically, 3-MCC is responsible for the fourth step in processing leucine, an amino acid that is part of many proteins.

Mutations in the MCCC1 or MCCC2 gene reduce or eliminate the activity of 3-MCC, preventing the body from processing leucine properly. As a result, toxic byproducts of leucine processing build up to harmful levels, which can damage the brain. This damage underlies the signs and symptoms of 3-MCC deficiency.

Related Gene(s)

Changes in these genes are associated with 3-methylcrotonyl-CoA carboxylase deficiency.

  • MCCC1
  • MCCC2

How do people inherit 3-MCC 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 3-MCC deficiency?

These resources address the diagnosis or management of 3-MCC deficiency and may include treatment providers.

  • Baby's First Test (http://www.babysfirsttest.org/newborn-screening/conditions/3-methylcrotonyl-coa-carboxylase-deficiency)
  • Gene Review: Organic Acidemias Overview (http://www.ncbi.nlm.nih.gov/books/NBK1134)
  • Genetic Testing Registry: 3 Methylcrotonyl-CoA carboxylase 1 deficiency (http://www.ncbi.nlm.nih.gov/gtr/conditions/CN028786)
  • Genetic Testing Registry: 3-methylcrotonyl CoA carboxylase 2 deficiency (http://www.ncbi.nlm.nih.gov/gtr/conditions/C1859499)
  • Genetic Testing Registry: Methylcrotonyl-CoA carboxylase deficiency (http://www.ncbi.nlm.nih.gov/gtr/conditions/C0268600)

You might also find information on the diagnosis or management of 3-MCC deficiency in Educational resources (http://www.ghr.nlm.nih.gov/condition/3-methylcrotonyl-coa-carboxylase-deficiency/show/Educational+resources) and Patient support (http://www.ghr.nlm.nih.gov/condition/3-methylcrotonyl-coa-carboxylase-deficiency/show/Patient+support).

General information about the diagnosis (http://ghr.nlm.nih.gov/handbook/consult/diagnosis) and management (http://ghr.nlm.nih.gov/handbook/consult/treatment) of genetic conditions is available in the Handbook. Read more about genetic testing (http://ghr.nlm.nih.gov/handbook/testing), particularly the difference between clinical tests and research tests (http://ghr.nlm.nih.gov/handbook/testing/researchtesting).

To locate a healthcare provider, see How can I find a genetics professional in my area? (http://ghr.nlm.nih.gov/handbook/consult/findingprofessional) in the Handbook.

Where can I find additional information about 3-MCC deficiency?

You may find the following resources about 3-MCC 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 3-MCC deficiency?

  • 3MCC
  • 3-MCC
  • 3-methylcrotonyl-coenzyme A carboxylase deficiency
  • 3-methylcrotonylglycinuria
  • BMCC deficiency
  • Deficiency of methylcrotonoyl-CoA carboxylase
  • MCC deficiency
  • Methylcrotonyl-CoA carboxylase deficiency

For more information about naming genetic conditions, see the Genetics Home Reference Condition Naming Guidelines (http://ghr.nlm.nih.gov/ConditionNameGuide) and How are genetic conditions and genes named? (http://ghr.nlm.nih.gov/handbook/mutationsanddisorders/naming) in the Handbook.

What if I still have specific questions about 3-MCC deficiency?

Ask the Genetic and Rare Diseases Information Center (http://rarediseases.info.nih.gov/GARD/).

What glossary definitions help with understanding 3-MCC deficiency?

amino acid ; autosomal ; autosomal recessive ; carboxylase ; cell ; CoA ; coenzyme A ; coma ; deficiency ; enzyme ; gene ; hypotonia ; inherited ; lethargy ; leucine ; metabolism ; muscle tone ; newborn screening ; protein ; recessive ; screening ; syndrome ; toxic

You may find definitions for these and many other terms in the Genetics Home Reference Glossary (http://www.ghr.nlm.nih.gov/glossary).

References

  • Arnold GL, Koeberl DD, Matern D, Barshop B, Braverman N, Burton B, Cederbaum S, Fiegenbaum A, Garganta C, Gibson J, Goodman SI, Harding C, Kahler S, Kronn D, Longo N. A Delphi-based consensus clinical practice protocol for the diagnosis and management of 3-methylcrotonyl CoA carboxylase deficiency. Mol Genet Metab. 2008 Apr;93(4):363-70. Epub 2007 Dec 21. (http://www.ncbi.nlm.nih.gov/pubmed/18155630?dopt=Abstract)
  • Baumgartner MR, Almashanu S, Suormala T, Obie C, Cole RN, Packman S, Baumgartner ER, Valle D. The molecular basis of human 3-methylcrotonyl-CoA carboxylase deficiency. J Clin Invest. 2001 Feb;107(4):495-504. (http://www.ncbi.nlm.nih.gov/pubmed/11181649?dopt=Abstract)
  • Gallardo ME, Desviat LR, Rodríguez JM, Esparza-Gordillo J, Pérez-Cerdá C, Pérez B, Rodríguez-Pombo P, Criado O, Sanz R, Morton DH, Gibson KM, Le TP, Ribes A, de Córdoba SR, Ugarte M, Peñalva MA. The molecular basis of 3-methylcrotonylglycinuria, a disorder of leucine catabolism. Am J Hum Genet. 2001 Feb;68(2):334-46. Epub 2001 Jan 17. (http://www.ncbi.nlm.nih.gov/pubmed/11170888?dopt=Abstract)
  • Holzinger A, Röschinger W, Lagler F, Mayerhofer PU, Lichtner P, Kattenfeld T, Thuy LP, Nyhan WL, Koch HG, Muntau AC, Roscher AA. Cloning of the human MCCA and MCCB genes and mutations therein reveal the molecular cause of 3-methylcrotonyl-CoA: carboxylase deficiency. Hum Mol Genet. 2001 Jun 1;10(12):1299-306. (http://www.ncbi.nlm.nih.gov/pubmed/11406611?dopt=Abstract)
  • Stadler SC, Polanetz R, Maier EM, Heidenreich SC, Niederer B, Mayerhofer PU, Lagler F, Koch HG, Santer R, Fletcher JM, Ranieri E, Das AM, Spiekerkötter U, Schwab KO, Pötzsch S, Marquardt I, Hennermann JB, Knerr I, Mercimek-Mahmutoglu S, Kohlschmidt N, Liebl B, Fingerhut R, Olgemöller B, Muntau AC, Roscher AA, Röschinger W. Newborn screening for 3-methylcrotonyl-CoA carboxylase deficiency: population heterogeneity of MCCA and MCCB mutations and impact on risk assessment. Hum Mutat. 2006 Aug;27(8):748-59. (http://www.ncbi.nlm.nih.gov/pubmed/16835865?dopt=Abstract)

 

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? (http://ghr.nlm.nih.gov/handbook/consult/findingprofessional) in the Handbook.

 
Reviewed: October 2008
Published: December 16, 2014