Skip Navigation
Genetics Home Reference: your guide to understanding genetic conditions
http://ghr.nlm.nih.gov/     A service of the U.S. National Library of Medicine®

Beta-ketothiolase deficiency

Reviewed January 2008

What is beta-ketothiolase deficiency?

Beta-ketothiolase deficiency is an inherited disorder in which the body cannot effectively process a protein building block (amino acid) called isoleucine. This disorder also impairs the body's ability to process ketones, which are molecules produced during the breakdown of fats.

The signs and symptoms of beta-ketothiolase deficiency typically appear between the ages of 6 months and 24 months. Affected children experience episodes of vomiting, dehydration, difficulty breathing, extreme tiredness (lethargy), and, occasionally, seizures. These episodes, which are called ketoacidotic attacks, sometimes lead to coma. Ketoacidotic attacks are frequently triggered by infections, periods without food (fasting), or increased intake of protein-rich foods.

How common is beta-ketothiolase deficiency?

Beta-ketothiolase deficiency appears to be very rare. It is estimated to affect fewer than 1 in 1 million newborns.

What genes are related to beta-ketothiolase deficiency?

Mutations in the ACAT1 gene cause beta-ketothiolase deficiency. This gene provides instructions for making an enzyme that is found in the energy-producing centers within cells (mitochondria). This enzyme plays an essential role in breaking down proteins and fats from the diet. Specifically, the ACAT1 enzyme helps process isoleucine, which is a building block of many proteins, and ketones, which are produced during the breakdown of fats.

Mutations in the ACAT1 gene reduce or eliminate the activity of the ACAT1 enzyme. A shortage of this enzyme prevents the body from processing proteins and fats properly. As a result, related compounds can build up to toxic levels in the blood. These substances cause the blood to become too acidic (ketoacidosis), which can damage the body's tissues and organs, particularly in the nervous system.

Related Gene(s)

Changes in this gene are associated with beta-ketothiolase deficiency.

  • ACAT1

How do people inherit beta-ketothiolase 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 beta-ketothiolase deficiency?

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

  • Baby's First Test (http://www.babysfirsttest.org/newborn-screening/conditions/beta-ketothiolase-deficiency)
  • Gene Review: Organic Acidemias (http://www.ncbi.nlm.nih.gov/books/NBK1134/)
  • Genetic Testing Registry: Deficiency of acetyl-CoA acetyltransferase (http://www.ncbi.nlm.nih.gov/gtr/conditions/C1536500)

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

You may find the following resources about beta-ketothiolase 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 beta-ketothiolase deficiency?

  • 2-alpha-methyl-3-hydroxybutyricacidemia
  • 3-alpha-ketothiolase deficiency
  • 3-alpha-ktd deficiency
  • 3-alpha-oxothiolase deficiency
  • alpha-Methylacetoacetic aciduria
  • β-ketothiolase deficiency
  • BKT
  • 3-Ketothiolase deficiency
  • MAT deficiency
  • 3-Methylhydroxybutyric acidemia
  • Mitochondrial 2-methylacetoacetyl-CoA thiolase deficiency - potassium stimulated
  • Mitochondrial acetoacetyl-CoA thiolase deficiency
  • T2 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 beta-ketothiolase deficiency?

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

What glossary definitions help with understanding beta-ketothiolase deficiency?

aciduria ; amino acid ; autosomal ; autosomal recessive ; cell ; CoA ; coma ; deficiency ; dehydration ; enzyme ; fasting ; gene ; isoleucine ; lethargy ; methyl ; mitochondria ; nervous system ; newborn screening ; potassium ; protein ; recessive ; screening ; 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

  • Fukao T, Scriver CR, Kondo N; t2 Collaborative Working Group. The clinical phenotype and outcome of mitochondrial acetoacetyl-CoA thiolase deficiency (beta-ketothiolase or T2 deficiency) in 26 enzymatically proved and mutation-defined patients. Mol Genet Metab. 2001 Feb;72(2):109-14. (http://www.ncbi.nlm.nih.gov/pubmed/11161836?dopt=Abstract)
  • Fukao T, Yamaguchi S, Orii T, Hashimoto T. Molecular basis of beta-ketothiolase deficiency: mutations and polymorphisms in the human mitochondrial acetoacetyl-coenzyme A thiolase gene. Hum Mutat. 1995;5(2):113-20. Review. (http://www.ncbi.nlm.nih.gov/pubmed/7749408?dopt=Abstract)
  • Fukao T, Zhang GX, Sakura N, Kubo T, Yamaga H, Hazama A, Kohno Y, Matsuo N, Kondo M, Yamaguchi S, Shigematsu Y, Kondo N. The mitochondrial acetoacetyl-CoA thiolase (T2) deficiency in Japanese patients: urinary organic acid and blood acylcarnitine profiles under stable conditions have subtle abnormalities in T2-deficient patients with some residual T2 activity. J Inherit Metab Dis. 2003;26(5):423-31. (http://www.ncbi.nlm.nih.gov/pubmed/14518824?dopt=Abstract)
  • Korman SH. Inborn errors of isoleucine degradation: a review. Mol Genet Metab. 2006 Dec;89(4):289-99. Epub 2006 Sep 6. Review. (http://www.ncbi.nlm.nih.gov/pubmed/16950638?dopt=Abstract)
  • Zhang GX, Fukao T, Rolland MO, Zabot MT, Renom G, Touma E, Kondo M, Matsuo N, Kondo N. Mitochondrial acetoacetyl-CoA thiolase (T2) deficiency: T2-deficient patients with "mild" mutation(s) were previously misinterpreted as normal by the coupled assay with tiglyl-CoA. Pediatr Res. 2004 Jul;56(1):60-4. Epub 2004 May 5. (http://www.ncbi.nlm.nih.gov/pubmed/15128923?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: January 2008
Published: April 21, 2014