MCID: ALP077
MIFTS: 37

Alpha-Methylacetoacetic Aciduria malady

Categories: Genetic diseases, Rare diseases, Metabolic diseases

Aliases & Classifications for Alpha-Methylacetoacetic Aciduria

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Aliases & Descriptions for Alpha-Methylacetoacetic Aciduria:

Name: Alpha-Methylacetoacetic Aciduria 51 25 12
Beta-Ketothiolase Deficiency 11 25 53 49 13
3-Ketothiolase Deficiency 11 47 25 53 69
Mitochondrial Acetoacetyl-Coa Thiolase Deficiency 11 47 25
Alpha-Methylacetoaceticaciduria 11 47 69
3-Oxothiolase Deficiency 11 47 53
2-Methyl-3-Hydroxybutyricacidemia 11 47
Pseudo-Zellweger Syndrome 38 67
T2 Deficiency 25 53
Mitochondrial 2-Methylacetoacetyl-Coa Thiolase Deficiency - Potassium Stimulated 25
Mitochondrial Acetoacetyl-Coenzyme a Thiolase Deficiency 53
Hepatic Methionine Adenosyltransferase Deficiency 67
Alpha-Methyl-Acetoacetyl-Coa Thiolase Deficiency 53
Bifunctional Peroxisomal Enzyme Deficiency 67
 
Deficiency of Acetyl-Coa Acetyltransferase 67
Deficiency of Acetyl-Coa Acyltransferase 67
2-Alpha-Methyl-3-Hydroxybutyricacidemia 25
Alpha Methylacetoacetic Aciduria 53
3-Methylhydroxybutyric Acidemia 25
Peroxisomal Thiolase Deficiency 11
3-Alpha-Ketothiolase Deficiency 25
3-Alpha-Oxothiolase Deficiency 25
Beta Ketothiolase Deficiency 47
β-Ketothiolase Deficiency 25
3-Alpha-Ktd Deficiency 25
Mat Deficiency 25
3ktd 69
Bkt 25

Characteristics:

Orphanet epidemiological data:

53
beta-ketothiolase deficiency:
Inheritance: Autosomal recessive; Prevalence: <1/1000000 (Worldwide),1-9/1000000 (Australia); Age of onset: Infancy; Age of death: adolescent

HPO:

63
alpha-methylacetoacetic aciduria:
Inheritance: autosomal recessive inheritance

Classifications:



External Ids:

OMIM51 203750
Disease Ontology11 DOID:14723
SNOMED-CT61 238067002
Orphanet53 ORPHA134
ICD10 via Orphanet30 E71.1
MedGen36 C1536500

Summaries for Alpha-Methylacetoacetic Aciduria

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NIH Rare Diseases:47 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: Alpha-Methylacetoacetic Aciduria, also known as beta-ketothiolase deficiency, is related to medium chain 3-ketothiolase deficiency and ketothiolase deficiency, and has symptoms including intellectual disability, dehydration and vomiting. An important gene associated with Alpha-Methylacetoacetic Aciduria is ACAT1 (Acetyl-CoA Acetyltransferase 1), and among its related pathways are Peroxisome and Peroxisomal lipid metabolism. Related mouse phenotype liver/biliary system.

Genetics Home Reference:25 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.

OMIM:51 Alpha-methylacetoacetic aciduria, also known as 3-ketothiolase deficiency, is an inborn error of isoleucine catabolism... (203750) more...

UniProtKB/Swiss-Prot:69 3-ketothiolase deficiency: An inborn error of isoleucine catabolism characterized by intermittent ketoacidotic attacks associated with unconsciousness. Some patients die during an attack or are mentally retarded. Urinary excretion of 2- methyl-3-hydroxybutyric acid, 2-methylacetoacetic acid, triglylglycine, butanone is increased. It seems likely that the severity of this disease correlates better with the environmental or acquired factors than with the ACAT1 genotype.

Related Diseases for Alpha-Methylacetoacetic Aciduria

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Graphical network of the top 20 diseases related to Alpha-Methylacetoacetic Aciduria:



Diseases related to alpha-methylacetoacetic aciduria

Symptoms for Alpha-Methylacetoacetic Aciduria

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Symptoms by clinical synopsis from OMIM:

203750

Clinical features from OMIM:

203750

Human phenotypes related to Alpha-Methylacetoacetic Aciduria:

 63
id Description HPO Frequency HPO Source Accession
1 intellectual disability63 HP:0001249
2 dehydration63 HP:0001944
3 vomiting63 HP:0002013
4 episodic ketoacidosis63 HP:0005974

UMLS symptoms related to Alpha-Methylacetoacetic Aciduria:


vomiting, acetonaemic vomiting

Drugs & Therapeutics for Alpha-Methylacetoacetic Aciduria

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Interventional clinical trials:

Search ClinicalTrials, NIH Clinical Center for Alpha-Methylacetoacetic Aciduria


Cochrane evidence based reviews: pseudo-zellweger syndrome

Genetic Tests for Alpha-Methylacetoacetic Aciduria

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Anatomical Context for Alpha-Methylacetoacetic Aciduria

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Animal Models for Alpha-Methylacetoacetic Aciduria or affiliated genes

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MGI Mouse Phenotypes related to Alpha-Methylacetoacetic Aciduria:

40
idDescriptionMGI Source AccessionScoreTop Affiliating Genes
1MP:00053708.4ACAD8, ACADM, ACADVL, HSD17B4, MAT1A

Publications for Alpha-Methylacetoacetic Aciduria

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Articles related to Alpha-Methylacetoacetic Aciduria:

idTitleAuthorsYear
1
A defect in l-isoleucine metabolism associated with alpha-methyl-beta-hydroxybutyric and alpha-methylacetoacetic aciduria: quantitative in vivo and in vitro studies. (4434646)
1974

Variations for Alpha-Methylacetoacetic Aciduria

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UniProtKB/Swiss-Prot genetic disease variations for Alpha-Methylacetoacetic Aciduria:

69
id Symbol AA change Variation ID SNP ID
1ACAT1p.Asn93SerVAR_007498rs120074145
2ACAT1p.Gly152AlaVAR_007499rs762991875
3ACAT1p.Asn158AspVAR_007500rs148639841
4ACAT1p.Gly183ArgVAR_007501rs120074141
5ACAT1p.Thr297MetVAR_007502
6ACAT1p.Ala301ProVAR_007503
7ACAT1p.Ile312ThrVAR_007504rs120074146
8ACAT1p.Ala333ProVAR_007505rs120074147
9ACAT1p.Gly379ValVAR_007506rs120074143
10ACAT1p.Ala380ThrVAR_007507rs120074140

Clinvar genetic disease variations for Alpha-Methylacetoacetic Aciduria:

5 (show all 35)
id Gene Variation Type Significance SNP ID Assembly Location
1ACAT1NM_000019.3(ACAT1): c.444_445delGG (p.Met148Ilefs)deletionPathogenicrs727503795GRCh37Chr 11, 108009633: 108009634
2ACAT1NM_000019.3(ACAT1): c.826+1G> TSNVPathogenicrs727503796GRCh37Chr 11, 108012428: 108012428
3ACAT1NM_000019.3(ACAT1): c.1006-4_1006-1delinsAAAindelPathogenicrs797044633GRCh37Chr 11, 108016925: 108016928
4ACAT1NM_000019.3(ACAT1): c.203G> T (p.Gly68Val)SNVLikely pathogenicrs794727475GRCh37Chr 11, 108004629: 108004629
5ACAT1NM_000019.3(ACAT1): c.455G> C (p.Gly152Ala)SNVLikely pathogenicrs762991875GRCh37Chr 11, 108009644: 108009644
6ACAT1NM_000019.3(ACAT1): c.473A> G (p.Asn158Ser)SNVPathogenicrs199524907GRCh37Chr 11, 108009662: 108009662
7ACAT1ACAT1, 1-BP DEL, 149CdeletionPathogenicChr na, -1: -1
8HSD17B4NM_000414.3(HSD17B4): c.302+1_302+4delGTGAdeletionPathogenicrs863225438GRCh37Chr 5, 118811423: 118811426
9ACAT1NM_000019.3(ACAT1): c.653C> T (p.Ser218Phe)SNVLikely pathogenicrs879255505GRCh38Chr 11, 108140138: 108140138
10ACAT1NM_000019.3(ACAT1): c.1138G> A (p.Ala380Thr)SNVPathogenicrs120074140GRCh37Chr 11, 108017061: 108017061
11ACAT1NM_000019.3(ACAT1): c.547G> A (p.Gly183Arg)SNVPathogenicrs120074141GRCh37Chr 11, 108009736: 108009736
12ACAT1ACAT1, IVS8, G-T, +1SNVPathogenicChr na, -1: -1
13ACAT1ACAT1, IVS10, A-C, -2SNVPathogenicChr na, -1: -1
14ACAT1ACAT1, IVS10, G-C, -1SNVPathogenicChr na, -1: -1
15ACAT1ACAT1, IVS11, T-C, +2SNVPathogenicChr na, -1: -1
16ACAT1NM_000019.3(ACAT1): c.2T> A (p.Met1Lys)SNVPathogenicrs120074142GRCh37Chr 11, 107992335: 107992335
17ACAT1NM_000019.3(ACAT1): c.1136G> T (p.Gly379Val)SNVPathogenicrs120074143GRCh37Chr 11, 108017059: 108017059
18ACAT1NM_000019.3(ACAT1): c.814C> T (p.Gln272Ter)SNVPathogenicrs120074144GRCh37Chr 11, 108012415: 108012415
19ACAT1NM_000019.3(ACAT1): c.1033_1035delGAA (p.Glu345del)deletionPathogenicrs387906282GRCh37Chr 11, 108016956: 108016958
20ACAT1NM_000019.3(ACAT1): c.1083dupA (p.Ala362Serfs)duplicationPathogenicrs387906283GRCh37Chr 11, 108017006: 108017006
21ACAT1NM_000019.3(ACAT1): c.278A> G (p.Asn93Ser)SNVPathogenicrs120074145GRCh37Chr 11, 108004987: 108004987
22ACAT1NM_000019.3(ACAT1): c.935T> C (p.Ile312Thr)SNVPathogenicrs120074146GRCh37Chr 11, 108013272: 108013272
23ACAT1NM_000019.3(ACAT1): c.997G> C (p.Ala333Pro)SNVPathogenicrs120074147GRCh37Chr 11, 108014766: 108014766
24ACAT1NM_000019.3(ACAT1): c.433C> G (p.Gln145Glu)SNVPathogenicrs120074148GRCh37Chr 11, 108005967: 108005967
25HSD17B4NM_000414.3(HSD17B4): c.1696_1702delCCAGTATinsAA (p.Pro566Lysfs)indelPathogenicrs886043708GRCh37Chr 5, 118862843: 118862849
26HSD17B4NM_000414.3(HSD17B4): c.1210_1261del52 (p.Val404Glufs)deletionPathogenicGRCh37Chr 5, 118837736: 118837787
27HSD17B4NM_000414.3(HSD17B4): c.973_1209del237 (p.Ala325_Lys403del)deletionPathogenicGRCh37Chr 5, 118835012: 118835248
28HSD17B4NM_000414.3(HSD17B4): c.46G> A (p.Gly16Ser)SNVLikely pathogenic, Pathogenicrs137853096GRCh37Chr 5, 118788316: 118788316
29HSD17B4NM_000414.3(HSD17B4): c.1369A> T (p.Asn457Tyr)SNVLikely pathogenic, Pathogenicrs137853097GRCh37Chr 5, 118844871: 118844871
30HSD17B4NM_000414.3(HSD17B4): c.317G> C (p.Arg106Pro)SNVPathogenicrs25640GRCh37Chr 5, 118811533: 118811533
31HSD17B4HSD17B4, 138-BP DELdeletionPathogenicChr na, -1: -1
32HSD17B4HSD17B4, 2-BP DEL, 422AGdeletionPathogenicChr na, -1: -1
33ACAT1NM_000019.3(ACAT1): c.472A> G (p.Asn158Asp)SNVPathogenicrs148639841GRCh37Chr 11, 108009661: 108009661
34ACAT1NM_000019.3(ACAT1): c.730+2T> CSNVPathogenicrs398123096GRCh37Chr 11, 108010944: 108010944
35ACAT1NM_000019.3(ACAT1): c.905delA (p.Lys302Argfs)deletionPathogenicrs398123097GRCh37Chr 11, 108013242: 108013242

Expression for genes affiliated with Alpha-Methylacetoacetic Aciduria

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Search GEO for disease gene expression data for Alpha-Methylacetoacetic Aciduria.

Pathways for genes affiliated with Alpha-Methylacetoacetic Aciduria

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Pathways related to Alpha-Methylacetoacetic Aciduria according to GeneCards Suite gene sharing:

(show all 13)
idSuper pathwaysScoreTop Affiliating Genes
19.6ACAA1, HSD17B4
2
Show member pathways
9.6ACAA1, HSD17B4
3
Show member pathways
9.6ACAA1, HSD17B4
49.3ACADM, ACAT1
59.1ACAA1, ACADM
6
Show member pathways
9.1ACADM, ACADVL
79.1ACADM, ACADVL
8
Show member pathways
8.9ACADM, ACAT1, MAT1A
9
Show member pathways
8.8ACADM, ACADVL, ACAT1
10
Show member pathways
8.8ACADM, ACADVL, ACAT1
11
Show member pathways
8.3ACAA1, ACADM, ACADVL, ACAT1
12
Show member pathways
7.8ACAA1, ACAD8, ACADM, ACAT1, HSD17B10
13
Show member pathways
6.4ACAA1, ACAD8, ACADM, ACADVL, ACAT1, HSD17B10

GO Terms for genes affiliated with Alpha-Methylacetoacetic Aciduria

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Cellular components related to Alpha-Methylacetoacetic Aciduria according to GeneCards Suite gene sharing:

idNameGO IDScoreTop Affiliating Genes
1peroxisomal matrixGO:000578210.1ACAA1, HSD17B4
2peroxisomeGO:00057779.1ACAA1, ACADM, HSD17B4
3mitochondrial matrixGO:00057598.0ACAD8, ACADM, ACADVL, ACAT1, HSD17B10
4mitochondrionGO:00057397.4ACAD8, ACADM, ACADVL, ACAT1, HSD17B10, HSD17B4

Biological processes related to Alpha-Methylacetoacetic Aciduria according to GeneCards Suite gene sharing:

(show all 9)
idNameGO IDScoreTop Affiliating Genes
1alpha-linolenic acid metabolic processGO:003610910.1ACAA1, HSD17B4
2fatty acid beta-oxidation using acyl-CoA oxidaseGO:00335409.9ACAA1, HSD17B4
3very long-chain fatty acid metabolic processGO:00000389.8ACAA1, HSD17B4
4liver developmentGO:00018899.3ACADM, ACAT1
5branched-chain amino acid catabolic processGO:00090839.1ACAD8, ACAT1, HSD17B10
6fatty acid beta-oxidation using acyl-CoA dehydrogenaseGO:00335399.0ACAD8, ACADM, ACADVL
7response to starvationGO:00425949.0ACADM, ACAT1
8lipid homeostasisGO:00550888.8ACAD8, ACADM, ACADVL
9fatty acid beta-oxidationGO:00066358.1ACAA1, ACADM, ACADVL, HSD17B4

Molecular functions related to Alpha-Methylacetoacetic Aciduria according to GeneCards Suite gene sharing:

idNameGO IDScoreTop Affiliating Genes
13-hydroxyacyl-CoA dehydrogenase activityGO:000385710.0HSD17B10, HSD17B4
2oxidoreductase activity, acting on the CH-CH group of donors, with a flavin as acceptorGO:00528909.0ACAD8, ACADM, ACADVL
3acyl-CoA dehydrogenase activityGO:00039959.0ACAD8, ACADM, ACADVL
4fatty-acyl-CoA bindingGO:00000628.9ACAD8, ACADM, ACADVL
5flavin adenine dinucleotide bindingGO:00506608.5ACAD8, ACADM, ACADVL
6electron carrier activityGO:00090558.4ACAD8, ACADM, ACADVL

Sources for Alpha-Methylacetoacetic Aciduria

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2CDC
6CNVD
10DGIdb
15ExPASy
16FDA
17FMA
26GTR
27HGMD
28HMDB
29ICD10
30ICD10 via Orphanet
31ICD9CM
32IUPHAR
33KEGG
36MedGen
38MeSH
39MESH via Orphanet
40MGI
43NCI
44NCIt
45NDF-RT
48NINDS
49Novoseek
51OMIM
52OMIM via Orphanet
56PubMed
57QIAGEN
62SNOMED-CT via Orphanet
66Tumor Gene Family of Databases
67UMLS
68UMLS via Orphanet