BKT
MCID: BTK001
MIFTS: 48

Beta-Ketothiolase Deficiency (BKT) malady

Genetic diseases, Rare diseases, Metabolic diseases categories
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Summaries for Beta-Ketothiolase Deficiency

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NIH Rare Diseases:42 Beta-ketothiolase deficiency is an inherited disorder in which the body cannot effectively process a protein building block (amino acid) called isoleucine. this condition also impairs the body's ability to process ketones, which are molecules produced during the breakdown of fats. signs and symptoms 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. this condition is inherited in an autosomal recessive fashion and is caused by mutations in the acat1 gene. last updated: 8/3/2011

MalaCards based summary: Beta-Ketothiolase Deficiency, also known as mitochondrial acetoacetyl-coa thiolase deficiency, is related to zellweger syndrome and ketothiolase deficiency, and has symptoms including An important gene associated with Beta-Ketothiolase Deficiency is ACAT1 (acetyl-CoA acetyltransferase 1), and among its related pathways are superpathway of cholesterol biosynthesis and Lysine degradation. The compounds isoleucine and n-acetylgalactosamine 6-sulfate have been mentioned in the context of this disorder.

Genetics Home Reference:21 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.

Wikipedia:65 Beta-ketothiolase deficiency is a rare, autosomal recessive metabolic disorder in which the body cannot... more...

Description from OMIM:46 203750

Aliases & Classifications for Beta-Ketothiolase Deficiency

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Beta-Ketothiolase Deficiency, Aliases & Descriptions:

Name: Beta-Ketothiolase Deficiency 8 21 10 44
Mitochondrial Acetoacetyl-Coa Thiolase Deficiency 8 42 21 62
Alpha-Methylacetoacetic Aciduria 9 21 46
3-Ketothiolase Deficiency 8 42 21
2-Methyl-3-Hydroxybutyricacidemia 8 42
Peroxisomal Thiolase Deficiency 8 62
Alpha-Methylacetoaceticaciduria 8 42
3-Oxothiolase Deficiency 8 42
Mat Deficiency 21 62
Bkt 21 62
Mitochondrial 2-Methylacetoacetyl-Coa Thiolase Deficiency - Potassium Stimulated 21
 
Alpha-Methyl-Acetoacetyl-Coa Thiolase Deficiency 48
Ketoacidosis Due to Beta-Ketothiolase Deficiency 48
Deficiency of Acetyl-Coa Acetyltransferase 62
2-Alpha-Methyl-3-Hydroxybutyricacidemia 21
3-Alpha-Ketothiolase Deficiency 21
3-Methylhydroxybutyric Acidemia 21
3-Alpha-Oxothiolase Deficiency 21
Beta Ketothiolase Deficiency 42
β-Ketothiolase Deficiency 21
3-Alpha-Ktd Deficiency 21
T2 Deficiency 21


Classifications:



Characteristics (Orphanet epidemiological data):

48
alpha-methyl-acetoacetyl-coa thiolase deficiency:
Inheritance: Autosomal recessive; Prevalence: <1/1000000; Age of onset: Neonatal/infancy


External Ids:

Disease Ontology8 DOID:14723
OMIM46 203750
SNOMED-CT57 238067002
MeSH34 C535818
ICD10 via Orphanet26 E71.1

Related Diseases for Beta-Ketothiolase Deficiency

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Graphical network of diseases related to Beta-Ketothiolase Deficiency:



Diseases related to beta-ketothiolase deficiency

Symptoms for Beta-Ketothiolase Deficiency

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Symptoms by clinical synopsis from OMIM:

203750

Clinical features from OMIM:

203750

HPO human phenotypes related to Beta-Ketothiolase Deficiency:

id Description Frequency HPO Source Accession
1 autosomal recessive inheritance HP:0000007
2 intellectual disability HP:0001249
3 dehydration HP:0001944
4 vomiting HP:0002013
5 episodic ketoacidosis HP:0005974

Drugs & Therapeutics for Beta-Ketothiolase Deficiency

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Drug clinical trials:

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Search NIH Clinical Center for Beta-Ketothiolase Deficiency

Genetic Tests for Beta-Ketothiolase Deficiency

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Anatomical Context for Beta-Ketothiolase Deficiency

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Animal Models for Beta-Ketothiolase Deficiency or affiliated genes

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Publications for Beta-Ketothiolase Deficiency

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Articles related to Beta-Ketothiolase Deficiency:

(show all 25)
idTitleAuthorsYear
1
NMR-based urinalysis for beta-ketothiolase deficiency. (25195009)
2014
2
A treatable new cause of chorea: beta-ketothiolase deficiency. (23818432)
2013
3
Beta-ketothiolase deficiency and pregnancy. (23664791)
2013
4
Metabolic encephalopathy in beta-ketothiolase deficiency: The first report from India. (23958592)
2013
5
MRI of Pallidal Involvement in Beta-Ketothiolase Deficiency. (23163837)
2012
6
Three Japanese Patients with Beta-Ketothiolase Deficiency Who Share a Mutation, c.431A&gt;C (H144P) in ACAT1 : Subtle Abnormality in Urinary Organic Acid Analysis and Blood Acylcarnitine Analysis Using Tandem Mass Spectrometry. (23430882)
2012
7
Beta-ketothiolase deficiency brought with lethargy: case report. (21247997)
2011
8
Enantioselective analysis of ketone bodies in patients with beta-ketothiolase deficiency, medium-chain acyl coenzyme A dehydrogenase deficiency and ketonemic vomiting. (10755375)
2000
9
Mitochondrial acetoacetyl-CoA thiolase (beta-ketothiolase) deficiency and pregnancy. (9700610)
1998
10
Molecular basis of Zellweger syndrome, beta-ketothiolase deficiency and mucopolysaccharidoses. (9183994)
1997
11
Identification of three novel frameshift mutations (83delAT, 754insCT, and 435 + 1G to A) of mitochondrial acetoacetyl-coenzyme A thiolase gene in two Swiss patients with CRM-negative beta-ketothiolase deficiency. (9090533)
1997
12
Mild form of beta-ketothiolase deficiency (mitochondrial acetoacetyl-CoA thiolase deficiency) in two Japanese siblings: identification of detectable residual activity and cross-reactive material in EB-transformed lymphocytes. (9001814)
1996
13
Molecular basis of beta-ketothiolase deficiency: mutations and polymorphisms in the human mitochondrial acetoacetyl-coenzyme A thiolase gene. (7749408)
1995
14
Mitochondrial acetoacetyl-coenzyme A thiolase gene: a novel 68-bp deletion involving 3' splice site of intron 7, causing exon 8 skipping in a Caucasian patient with beta-ketothiolase deficiency. (7728155)
1995
15
Induction of fetal hemoglobin in the presence of increased 3-hydroxybutyric acid associated with beta-ketothiolase deficiency. (7520129)
1994
16
Beta-ketothiolase deficiency. A case report. (1509529)
1992
17
beta-Ketothiolase deficiency with favourable evolution. (3126364)
1987
18
Characterization of new diagnostic acylcarnitines in patients with beta-ketothiolase deficiency and glutaric aciduria type I using mass spectrometry. (3435793)
1987
19
Two cases of beta-ketothiolase deficiency: a comparison. (6434866)
1984
20
A case of beta-ketothiolase deficiency. (6422156)
1983
21
The occurrence of substituted 3-methyl-3-hydroxyglutaric acids in urine in propionic acidaemia and in beta-ketothiolase deficiency. (6133567)
1983
22
The identification of (E)-2-methylglutaconic acid, a new isoleucine metabolite, in the urine of patients with beta-ketothiolase deficiency, propionic acidaemia and methylmalonic acidaemia. (7059658)
1982
23
Beta-ketothiolase deficiency in a family confirmed by in vitro enzymatic assays in fibroblasts. (7173255)
1982
24
Congestive cardiomyopathy associated with beta-ketothiolase deficiency. (7299555)
1981
25
Beta-ketothiolase deficiency as a cause of the &quot;ketotic hyperglycinemia syndrome&quot;. (4812006)
1974

Variations for Beta-Ketothiolase Deficiency

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UniProtKB/Swiss-Prot genetic disease variations for Beta-Ketothiolase Deficiency:

64
id Symbol AA change Variation ID SNP ID
1ACAT1p.Asn93SerVAR_007498
2ACAT1p.Gly152AlaVAR_007499
3ACAT1p.Asn158AspVAR_007500
4ACAT1p.Gly183ArgVAR_007501
5ACAT1p.Thr297MetVAR_007502
6ACAT1p.Ala301ProVAR_007503
7ACAT1p.Ile312ThrVAR_007504
8ACAT1p.Ala333ProVAR_007505
9ACAT1p.Gly379ValVAR_007506
10ACAT1p.Ala380ThrVAR_007507

Clinvar genetic disease variations for Beta-Ketothiolase Deficiency:

6 (show all 15)
id Gene Name Type Significance SNP ID Assembly Location
1ACAT1NM_000019.3(ACAT1): c.1138G> A (p.Ala380Thr)single nucleotide variantPathogenicrs120074140GRCh37Chr 11, 108017061: 108017061
2ACAT1NM_000019.3(ACAT1): c.547G> A (p.Gly183Arg)single nucleotide variantPathogenicrs120074141GRCh37Chr 11, 108009736: 108009736
3ACAT1ACAT1, IVS8, G-T, +1single nucleotide variantPathogenic
4ACAT1ACAT1, IVS10, A-C, -2single nucleotide variantPathogenic
5ACAT1ACAT1, IVS10, G-C, -1single nucleotide variantPathogenic
6ACAT1ACAT1, IVS11, T-C, +2single nucleotide variantPathogenic
7ACAT1NM_000019.3(ACAT1): c.2T> A (p.Met1Lys)single nucleotide variantPathogenicrs120074142GRCh37Chr 11, 107992335: 107992335
8ACAT1NM_000019.3(ACAT1): c.1136G> T (p.Gly379Val)single nucleotide variantPathogenicrs120074143GRCh37Chr 11, 108017059: 108017059
9ACAT1NM_000019.3(ACAT1): c.814C> T (p.Gln272Ter)single nucleotide variantPathogenicrs120074144GRCh37Chr 11, 108012415: 108012415
10ACAT1NM_000019.3(ACAT1): c.1033_1035delGAA (p.Glu345del)deletionPathogenicrs387906282GRCh37Chr 11, 108016956: 108016958
11ACAT1NM_000019.3(ACAT1): c.1083dupA (p.Ala362Serfs)duplicationPathogenicrs387906283GRCh37Chr 11, 108017006: 108017007
12ACAT1NM_000019.3(ACAT1): c.278A> G (p.Asn93Ser)single nucleotide variantPathogenicrs120074145GRCh37Chr 11, 108004987: 108004987
13ACAT1NM_000019.3(ACAT1): c.935T> C (p.Ile312Thr)single nucleotide variantPathogenicrs120074146GRCh37Chr 11, 108013272: 108013272
14ACAT1NM_000019.3(ACAT1): c.997G> C (p.Ala333Pro)single nucleotide variantPathogenicrs120074147GRCh37Chr 11, 108014766: 108014766
15ACAT1NM_000019.3(ACAT1): c.433C> G (p.Gln145Glu)single nucleotide variantPathogenicrs120074148GRCh37Chr 11, 108005967: 108005967

Expression for genes affiliated with Beta-Ketothiolase Deficiency

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Expression patterns in normal tissues for genes affiliated with Beta-Ketothiolase Deficiency

Search GEO for disease gene expression data for Beta-Ketothiolase Deficiency.

Pathways for genes affiliated with Beta-Ketothiolase Deficiency

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Pathways related to Beta-Ketothiolase Deficiency according to GeneCards/GeneDecks:

(show all 16)
idSuper pathways (with members indented)ScoreTop Affiliating Genes
1
Show member pathways
Cholesterol biosynthesis37
lanosterol biosynthesis37
zymosterol biosynthesis37
mevalonate pathway I37
epoxysqualene biosynthesis37
cholesterol biosynthesis II (via 24,25-dihydrolanosterol)37
superpathway of geranylgeranyldiphosphate biosynthesis I (via mevalonate)37
trans, trans-farnesyl diphosphate biosynthesis37
cholesterol biosynthesis I37
cholesterol biosynthesis III (via desmosterol)37
geranylgeranyldiphosphate biosynthesis37
9.7ACAT2, ACAT1
29.7ACAT2, ACAT1
39.7ACAT1, ACAT2
4
Show member pathways
methylglyoxal degradation VI37
methylglyoxal degradation I37
9.7ACAT1, ACAT2
5
Show member pathways
tryptophan degradation X (mammalian, via tryptamine)37
2-amino-3-carboxymuconate semialdehyde degradation to glutaryl-CoA37
tryptophan degradation37
glutaryl-CoA degradation37
serotonin degradation37
NAD de novo biosynthesis37
superpathway of melatonin degradation37
tryptophan degradation to 2-amino-3-carboxymuconate semialdehyde37
tryptophan utilization I37
melatonin degradation I37
9.7ACAT1, ACAT2
6
Show member pathways
fatty acid beta-oxidation I37
eicosapentaenoate biosynthesis II (metazoa)37
gamma-linolenate biosynthesis II (animals)37
fatty acid activation37
9.7ACAA2, HSD17B10
7
Show member pathways
creatine-phosphate biosynthesis37
glycine degradation (creatine biosynthesis)37
putrescine biosynthesis III37
spermidine biosynthesis I37
tryptophan degradation via kynurenine37
spermine biosynthesis37
urea cycle37
S-methyl-5-thio-alpha-D-ribose 1-phosphate degradation I37
tyrosine degradation I37
L-carnitine biosynthesis37
methylthiopropionate biosynthesis37
2-oxoglutarate decarboxylation to succinyl-CoA37
S-methyl-5-thioadenosine degradation II37
9.6MAT1A, ACAT1, HSD17B10
8
Show member pathways
Synthesis and Degradation of Ketone Bodies37
ketolysis37
9.6HMGCL, ACAT1
9
Show member pathways
9.4ACAT2, ACAT1, HSD17B10
10
Show member pathways
L-serine degradation37
pentose phosphate pathway (oxidative branch)37
formaldehyde oxidation II (glutathione-dependent)37
9.4ACAT1, ACAT2, MAT1A
11
Show member pathways
oleate biosynthesis II (animals)37
9.1ACAA2, ACAA1
12
Show member pathways
9.1ACAT1, ACAT2, HMGCL
13
Show member pathways
mitochondrial L-carnitine shuttle pathway37
Saturated fatty acid biosynthesis60
8.4ACAT1, ACAA1, ACAT2, ACAA2
148.2HMGCL, ACAA1, PEX6, PEX2
15
Show member pathways
beta-alanine degradation I37
valine degradation I37
pyruvate fermentation to lactate37
isoleucine degradation I37
7.5HMGCL, HSD17B10, ACAT1, ACAA1, ACAT2, ACAA2
16
Show member pathways
6.3HSD17B10, ACAT1, ACAA1, ACAT2, ACAA2, MAT1A

Compounds for genes affiliated with Beta-Ketothiolase Deficiency

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Sources:
44Novoseek, 24HMDB, 11DrugBank
See all sources

Compounds related to Beta-Ketothiolase Deficiency according to GeneCards/GeneDecks:

(show all 30)
idCompoundScoreTop Affiliating Genes
1isoleucine449.9ACAT1, HSD17B10
2n-acetylgalactosamine 6-sulfate449.9GALNS, ARSH
317beta-hydroxysteroid449.8HSD17B10, ARSH
4glucuronic acid449.7ARSH, GALNS
5acetoacetyl coa449.6ACAT1, ACAT2, ACAA2
6CoA-omega-COOH-dinor-LTE4249.5ACAA1, ACAA2
77'-carboxy-gama-tocotrienol249.5ACAA1, ACAA2
87'-carboxy-alpha-tocotrienol249.5ACAA1, ACAA2
95'-Carboxy-gama-chromanol249.5ACAA1, ACAA2
105'-Carboxy-alpha-chromanol249.5ACAA1, ACAA2
11Chenodeoxyglycocholoyl-CoA249.4ACAA1, ACAA2
12Chenodeoxycholoyl-CoA249.4ACAA1, ACAA2
133a,7a,12a-Trihydroxy-5b-24-oxocholestanoyl-CoA249.4ACAA1, ACAA2
143a,7a-Dihydroxy-5b-cholestanoyl-CoA249.4ACAA1, ACAA2
15Choloyl-CoA249.4ACAA2, ACAA1
163-Oxotetradecanoyl-CoA249.4ACAA1, ACAA2
173-Oxododecanoyl-CoA249.4ACAA1, ACAA2
183-Oxodecanoyl-CoA249.3ACAA2, ACAA1
19glucosamine44 24 1111.3ARSH, GALNS
20Tetradecanoyl-CoA249.3ACAA1, ACAA2
212-Methylacetoacetyl-CoA249.2HSD17B10, ACAA1, ACAA2
223-Oxooctanoyl-CoA249.2HSD17B10, ACAA1, ACAA2
233-Oxohexadecanoyl-CoA249.2HSD17B10, ACAA1, ACAA2
24Heptanoyl-CoA249.0ACAA2, ACAA1, HSD17B10
25lipid448.8ARSH, MAT1A, ACAT2, HSD17B10, PEX2
263-Oxohexanoyl-CoA248.8ACAT1, ACAA1, ACAT2, ACAA2
27Coenzyme A24 119.7ACAT1, ACAA1, ACAT2, ACAA2
28cysteine448.6ARSH, GALNS, HMGCL, MAT1A
29Acetoacetyl-CoA248.5ACAA2, ACAT2, ACAA1, ACAT1, HSD17B10
30acetyl-coa44 249.1ACAT1, ACAA1, ACAT2, ACAA2, HMGCL

GO Terms for genes affiliated with Beta-Ketothiolase Deficiency

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Cellular components related to Beta-Ketothiolase Deficiency according to GeneCards/GeneDecks:

idNameGO IDScoreTop Affiliating Genes
1peroxisomal membraneGO:0057789.4PEX6, PEX2
2mitochondrial matrixGO:0057599.2HSD17B10, ACAT1, HMGCL
3mitochondrial inner membraneGO:0057438.8HMGCL, ACAA2, ACAT1, HSD17B10
4mitochondrionGO:0057398.7HMGCL, ACAA2, ACAT1, HSD17B10
5peroxisomeGO:0057778.6HMGCL, ACAA1, PEX6

Biological processes related to Beta-Ketothiolase Deficiency according to GeneCards/GeneDecks:

(show all 11)
idNameGO IDScoreTop Affiliating Genes
1branched-chain amino acid catabolic processGO:00908310.0ACAT1, HSD17B10
2cellular ketone body metabolic processGO:0469509.8ACAT1, HMGCL
3ketone body biosynthetic processGO:0469519.8ACAT1, HMGCL
4peroxisome organizationGO:0070319.8PEX6, PEX2
5cellular nitrogen compound metabolic processGO:0346419.6HSD17B10, MAT1A, ACAT1
6liver developmentGO:0018899.6ACAT1, HMGCL
7response to starvationGO:0425949.5HMGCL, ACAT1
8very long-chain fatty acid metabolic processGO:0000389.5ACAA1, PEX2
9fatty acid beta-oxidationGO:0066359.0PEX2, ACAA1
10cellular lipid metabolic processGO:0442558.9HMGCL, ACAA1, ACAT1
11small molecule metabolic processGO:0442817.5ACAA1, ARSH, HSD17B10, ACAT1, GALNS, MAT1A

Molecular functions related to Beta-Ketothiolase Deficiency according to GeneCards/GeneDecks:

idNameGO IDScoreTop Affiliating Genes
1acetyl-CoA C-acyltransferase activityGO:0039888.8ACAA2, ACAA1
2metal ion bindingGO:0468728.4ARSH, GALNS, HMGCL, MAT1A, ACAT1

Products for genes affiliated with Beta-Ketothiolase Deficiency

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  • Antibodies
  • Proteins
  • Lysates

Sources for Beta-Ketothiolase Deficiency

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3CDC
13ExPASy
14FMA
22GTR
23HGMD
24HMDB
25ICD10
26ICD10 via Orphanet
27ICD9CM
28IUPHAR
29KEGG
34MeSH
35MESH via Orphanet
36MGI
39NCIt
40NDF-RT
43NINDS
44Novoseek
46OMIM
47OMIM via Orphanet
51PubMed
52QIAGEN
58SNOMED-CT via Orphanet
62UMLS
63UMLS via Orphanet