Display Settings:

Format

Send to:

Choose Destination
We are sorry, but NCBI web applications do not support your browser and may not function properly. More information

Deficiency of acetyl-CoA acetyltransferase

MedGen UID:
280689
Concept ID:
C1536500
Disease or Syndrome
Synonyms: Deficiency of acetyl-CoA acetyltransferase; 2-alpha-methyl-3-hydroxybutyricacidemia; 2-methyl-3-hydroxybutyricacidemia; 3-alpha-ketothiolase deficiency; 3-alpha-ktd deficiency; 3-alpha-oxothiolase deficiency; 3-ketothiolase deficiency; 3-Methylhydroxybutyric acidemia; 3-oxothiolase deficiency; Alpha-methylacetoaceticaciduria; Beta ketothiolase deficiency; Ketothiolase Deficiency; MAT deficiency; Mitochondrial 2-methylacetoacetyl-CoA thiolase deficiency - potassium stimulated; Mitochondrial acetoacetyl-CoA Thiolase deficiency; T2 deficiency; β-ketothiolase deficiency
Modes of inheritance:
Autosomal recessive inheritance
MedGen UID:
141025
Concept ID:
C0441748
Intellectual Product
Autosomal recessive inheritance refers to genetic conditions that occur only when mutations are present in both copies of a given gene (i.e., the person is homozygous for a mutation, or carries two different mutations of the same gene, a state referred to as compound heterozygosity).
SNOMED CT: Acetoacetyl-CoA thiolase deficiency (124258007); 3-Ketothiolase deficiency (124258007); Deficiency of acetoacetyl-CoA thiolase (124258007); Deficiency of acetyl-CoA acetyltransferase (124258007); alpha-Methylacetoacetic aciduria (124258007); 3-Methylhydroxybutyric acidemia (124258007); Deficiency of acetyl-coenzyme A acetyltransferase (124258007)
 
Gene: ACAT1
Cytogenetic location: 11q22.3
OMIM: 203750

Disease characteristics

Excerpted from the GeneReview: The Organic Acidemias: An Overview
The term "organic acidemia" or "organic aciduria" (OA) applies to a group of disorders characterized by the excretion of non-amino organic acids in urine. Most organic acidemias result from dysfunction of a specific step in amino acid catabolism, usually the result of deficient enzyme activity. The majority of the classic organic acid disorders are caused by abnormal amino acid catabolism of branched-chain amino acids or lysine. They include maple syrup urine disease (MSUD), propionic acidemia, methylmalonic acidemia (MMA), methylmalonic aciduria and homocystinuria, isovaleric acidemia, biotin-unresponsive 3-methylcrotonyl-CoA carboxylase deficiency, 3-hydroxy-3-methylglutaryl-CoA (HMG-CoA) lyase deficiency, ketothiolase deficiency, and glutaricacidemia type I (GA I). A neonate affected with an OA is usually well at birth and for the first few days of life. The usual clinical presentation is that of toxic encephalopathy and includes vomiting, poor feeding, neurologic symptoms such as seizures and abnormal tone, and lethargy progressing to coma. Outcome is enhanced by diagnosis and treatment in the first ten days of life. In the older child or adolescent, variant forms of the OAs can present as loss of intellectual function, ataxia or other focal neurologic signs, Reye syndrome, recurrent ketoacidosis, or psychiatric symptoms.  [from GeneReviews]
Full text of GeneReview (by section):
Summary  |  Definition  |  Causes  |  Evaluation Strategy  |  Genetic Counseling  |  Resources  |  Management  |  References  |  Chapter Notes
Authors:
Margretta R Seashore   view full author information

Additional descriptions

From OMIM
This disorder, initially called alpha-methylacetoacetic aciduria, and more recently 3-oxothiolase deficiency, is an inborn error of isoleucine catabolism characterized by urinary excretion of 2-methyl-3-hydroxybutyric acid, 2-methylacetoacetic acid, tiglylglycine, and 2-butanone.  http://www.omim.org/entry/203750
From GHR
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.  http://ghr.nlm.nih.gov/condition/beta-ketothiolase-deficiency

Clinical features

Intellectual disability
MedGen UID:
334384
Concept ID:
C1843367
Finding
Episodic ketoacidosis
MedGen UID:
349256
Concept ID:
C1859860
Finding
Vomiting
MedGen UID:
776588
Concept ID:
C2712332
Finding
Dehydration
MedGen UID:
776589
Concept ID:
C2712335
Finding

Recent clinical studies

Etiology

Durand S, Feldhammer M, Bonneil E, Thibault P, Pshezhetsky AV
J Biol Chem 2010 Oct 8;285(41):31233-42. Epub 2010 Jul 22 doi: 10.1074/jbc.M110.141150. [Epub ahead of print] PMID: 20650889Free PMC Article
Fukao T, Nguyen HT, Nguyen NT, Vu DC, Can NT, Pham AT, Nguyen KN, Kobayashi H, Hasegawa Y, Bui TP, Niezen-Koning KE, Wanders RJ, de Koning T, Nguyen LT, Yamaguchi S, Kondo N
Mol Genet Metab 2010 May;100(1):37-41. Epub 2010 Jan 21 doi: 10.1016/j.ymgme.2010.01.007. [Epub ahead of print] PMID: 20156697
Papadopoulos P, Bousette N, Al-Ramli W, You Z, Behm DJ, Ohlstein EH, Harrison SM, Douglas SA, Giaid A
Atherosclerosis 2009 Jun;204(2):395-404. Epub 2008 Nov 21 doi: 10.1016/j.atherosclerosis.2008.10.044. [Epub ahead of print] PMID: 19111831
Korman SH
Mol Genet Metab 2006 Dec;89(4):289-99. Epub 2006 Sep 6 doi: 10.1016/j.ymgme.2006.07.010. [Epub ahead of print] PMID: 16950638
Fukao T, Zhang GX, Sakura N, Kubo T, Yamaga H, Hazama A, Kohno Y, Matsuo N, Kondo M, Yamaguchi S, Shigematsu Y, Kondo N
J Inherit Metab Dis 2003;26(5):423-31. PMID: 14518824

Diagnosis

Fukao T, Horikawa R, Naiki Y, Tanaka T, Takayanagi M, Yamaguchi S, Kondo N
Mol Genet Metab 2010 Aug;100(4):339-44. Epub 2010 Mar 19 doi: 10.1016/j.ymgme.2010.03.012. [Epub ahead of print] PMID: 20488739
Catanzano F, Ombrone D, Di Stefano C, Rossi A, Nosari N, Scolamiero E, Tandurella I, Frisso G, Parenti G, Ruoppolo M, Andria G, Salvatore F
J Inherit Metab Dis 2010 Dec;33 Suppl 3:S91-4. Epub 2010 Feb 16 doi: 10.1007/s10545-009-9028-3. [Epub ahead of print] PMID: 20157782Free PMC Article
Fukao T, Nguyen HT, Nguyen NT, Vu DC, Can NT, Pham AT, Nguyen KN, Kobayashi H, Hasegawa Y, Bui TP, Niezen-Koning KE, Wanders RJ, de Koning T, Nguyen LT, Yamaguchi S, Kondo N
Mol Genet Metab 2010 May;100(1):37-41. Epub 2010 Jan 21 doi: 10.1016/j.ymgme.2010.01.007. [Epub ahead of print] PMID: 20156697
Thümmler S, Dupont D, Acquaviva C, Fukao T, de Ricaud D
Tohoku J Exp Med 2010 Jan;220(1):27-31. PMID: 20046049
Tilbrook LK, Slater J, Agarwal A, Cyriac J
Ann Clin Biochem 2008 Sep;45(Pt 5):524-6. doi: 10.1258/acb.2008.007202. PMID: 18753430

Therapy

Kim SJ, Kang S, Kim JB
Gene 2012 Aug 10;504(2):156-9. Epub 2012 May 24 doi: 10.1016/j.gene.2012.05.036. [Epub ahead of print] PMID: 22634098
Wierzbicki AS, Hardman TC, Viljoen A
Int J Clin Pract 2012 Mar;66(3):270-80. doi: 10.1111/j.1742-1241.2011.02867.x. PMID: 22340447
Fan X, Tkachyova I, Sinha A, Rigat B, Mahuran D
PLoS One 2011;6(9):e24951. Epub 2011 Sep 21 doi: 10.1371/journal.pone.0024951. PMID: 21957468Free PMC Article
Nagashima M, Watanabe T, Shiraishi Y, Morita R, Terasaki M, Arita S, Hongo S, Sato K, Shichiri M, Miyazaki A, Hirano T
Atherosclerosis 2010 Sep;212(1):70-7. Epub 2010 May 4 doi: 10.1016/j.atherosclerosis.2010.04.027. [Epub ahead of print] PMID: 20684826
Xu G, Watanabe T, Iso Y, Koba S, Sakai T, Nagashima M, Arita S, Hongo S, Ota H, Kobayashi Y, Miyazaki A, Hirano T
Circ Res 2009 Aug 28;105(5):500-10. Epub 2009 Jul 30 doi: 10.1161/CIRCRESAHA.109.193870. [Epub ahead of print] PMID: 19644050

Prognosis

Athanasiadis P, Malousi A, Kouidou S, Maglaveras N
Comput Methods Programs Biomed 2013 Jul;111(1):214-9. Epub 2013 May 4 doi: 10.1016/j.cmpb.2013.04.002. [Epub ahead of print] PMID: 23648050
Puisac B, Teresa-Rodrigo ME, Arnedo M, Gil-Rodríguez MC, Pérez-Cerdá C, Ribes A, Pié A, Bueno G, Gómez-Puertas P, Pié J
Mol Genet Metab 2013 Apr;108(4):232-40. Epub 2013 Feb 4 doi: 10.1016/j.ymgme.2013.01.019. [Epub ahead of print] PMID: 23465862
Catanzano F, Ombrone D, Di Stefano C, Rossi A, Nosari N, Scolamiero E, Tandurella I, Frisso G, Parenti G, Ruoppolo M, Andria G, Salvatore F
J Inherit Metab Dis 2010 Dec;33 Suppl 3:S91-4. Epub 2010 Feb 16 doi: 10.1007/s10545-009-9028-3. [Epub ahead of print] PMID: 20157782Free PMC Article
Reimão S, Morgado C, Almeida IT, Silva M, Corte Real H, Campos J
J Inherit Metab Dis 2009 Dec;32 Suppl 1:S49-52. Epub 2009 Feb 24 doi: 10.1007/s10545-009-1048-5. [Epub ahead of print] PMID: 19242819
Korman SH
Mol Genet Metab 2006 Dec;89(4):289-99. Epub 2006 Sep 6 doi: 10.1016/j.ymgme.2006.07.010. [Epub ahead of print] PMID: 16950638

Clinical prediction guides

Athanasiadis P, Malousi A, Kouidou S, Maglaveras N
Comput Methods Programs Biomed 2013 Jul;111(1):214-9. Epub 2013 May 4 doi: 10.1016/j.cmpb.2013.04.002. [Epub ahead of print] PMID: 23648050
Puisac B, Teresa-Rodrigo ME, Arnedo M, Gil-Rodríguez MC, Pérez-Cerdá C, Ribes A, Pié A, Bueno G, Gómez-Puertas P, Pié J
Mol Genet Metab 2013 Apr;108(4):232-40. Epub 2013 Feb 4 doi: 10.1016/j.ymgme.2013.01.019. [Epub ahead of print] PMID: 23465862
Isaac DT, Coady A, Van Prooyen N, Sil A
Infect Immun 2013 Feb;81(2):411-20. Epub 2012 Nov 26 doi: 10.1128/IAI.00833-12. [Epub ahead of print] PMID: 23184522Free PMC Article
Catanzano F, Ombrone D, Di Stefano C, Rossi A, Nosari N, Scolamiero E, Tandurella I, Frisso G, Parenti G, Ruoppolo M, Andria G, Salvatore F
J Inherit Metab Dis 2010 Dec;33 Suppl 3:S91-4. Epub 2010 Feb 16 doi: 10.1007/s10545-009-9028-3. [Epub ahead of print] PMID: 20157782Free PMC Article
Xu G, Watanabe T, Iso Y, Koba S, Sakai T, Nagashima M, Arita S, Hongo S, Ota H, Kobayashi Y, Miyazaki A, Hirano T
Circ Res 2009 Aug 28;105(5):500-10. Epub 2009 Jul 30 doi: 10.1161/CIRCRESAHA.109.193870. [Epub ahead of print] PMID: 19644050

Supplemental Content

Recent activity

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...