MCID: ALP077
MIFTS: 41

Alpha-Methylacetoacetic Aciduria

Categories: Genetic diseases, Rare diseases, Metabolic diseases

Aliases & Classifications for Alpha-Methylacetoacetic Aciduria

MalaCards integrated aliases for Alpha-Methylacetoacetic Aciduria:

Name: Alpha-Methylacetoacetic Aciduria 53 24 36 13
Beta-Ketothiolase Deficiency 53 12 24 55 51 14
3-Ketothiolase Deficiency 53 12 49 24 55 71
Mitochondrial Acetoacetyl-Coa Thiolase Deficiency 53 12 49 24
3-Oxothiolase Deficiency 53 12 49 55
Alpha-Methylacetoaceticaciduria 12 49 71
T2 Deficiency 53 24 55
2-Methyl-3-Hydroxybutyricacidemia 12 49
Beta Ketothiolase Deficiency 72 49
Pseudo-Zellweger Syndrome 41 69
Mat Deficiency 53 24
Mitochondrial 2-Methylacetoacetyl-Coa Thiolase Deficiency - Potassium Stimulated 24
Mitochondrial Acetoacetyl-Coenzyme a Thiolase Deficiency 55
Hepatic Methionine Adenosyltransferase Deficiency 69
Alpha-Methyl-Acetoacetyl-Coa Thiolase Deficiency 55
Bifunctional Peroxisomal Enzyme Deficiency 69
Deficiency of Acetyl-Coa Acetyltransferase 69
Deficiency of Acetyl-Coa Acyltransferase 69
2-Alpha-Methyl-3-Hydroxybutyricacidemia 24
2-Methyl-3-Hydroxybutyric Acidemia 53
Alpha Methylacetoacetic Aciduria 55
Peroxisomal Thiolase Deficiency 12
3-Alpha-Ketothiolase Deficiency 24
3-Methylhydroxybutyric Acidemia 24
3-Alpha-Oxothiolase Deficiency 24
Β-Ketothiolase Deficiency 24
3-Alpha-Ktd Deficiency 24
3-Ktd Deficiency 53
3ktd 71
Bkt 24

Characteristics:

Orphanet epidemiological data:

55
beta-ketothiolase deficiency
Inheritance: Autosomal recessive; Prevalence: <1/1000000 (Worldwide),1-9/1000000 (Australia); Age of onset: Infancy; Age of death: adolescent;

OMIM:

53
Inheritance:
autosomal recessive

Miscellaneous:
onset at 5-24 months
infections may precipitate ketotic episodes
patients with t2 deficiency and urinary abnormalities may be asymptomatic


HPO:

31
alpha-methylacetoacetic aciduria:
Inheritance autosomal recessive inheritance


Classifications:

Orphanet: 55  
Inborn errors of metabolism


External Ids:

OMIM 53 203750
Disease Ontology 12 DOID:14723
SNOMED-CT 64 238067002
Orphanet 55 ORPHA134
UMLS via Orphanet 70 C1536500
ICD10 via Orphanet 33 E71.1
MedGen 39 C1536500
KEGG 36 H01076

Summaries for Alpha-Methylacetoacetic Aciduria

NIH Rare Diseases : 49 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 and 24 months. Affected children experience intermittent episodes of ketoacidosis, characterized by vomiting, dehydration, difficulty breathing, extreme tiredness (lethargy), and occasionally, seizures. In severe cases, these episodes can lead to coma. Metabolic stroke is another finding that has been increasingly reported in children with this condition. Ketoacidotic attacks are frequently triggered by infections, periods without food (fasting), or increased intake of protein-rich foods.  Beta ketothiolase deficiency is inherited in an autosomal recessive fashion and is caused by pathogenic variants (mutations) in the ACAT1 gene. Treatment involves managing acute crises with intravenous (IV) fluids, glucose, and electrolytes along with bicarbonate. Long-term management involves eating frequently, following a reduced-protein diet, avoidance of high-fat foods, and, in some cases, carnitine supplementation.  Last updated: 6/28/2017

MalaCards based summary : Alpha-Methylacetoacetic Aciduria, also known as beta-ketothiolase deficiency, is related to methionine adenosyltransferase i/iii deficiency and d-bifunctional protein 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/superpathways are Valine, leucine and isoleucine degradation and Synthesis and degradation of ketone bodies.

Genetics Home Reference : 24 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 : 53 Alpha-methylacetoacetic aciduria, also known as 3-ketothiolase 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. (203750)

UniProtKB/Swiss-Prot : 71 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.

Wikipedia : 72 Beta-ketothiolase deficiency is a rare, autosomal recessive metabolic disorder in which the body cannot... more...

Related Diseases for Alpha-Methylacetoacetic Aciduria

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



Diseases related to Alpha-Methylacetoacetic Aciduria

Symptoms & Phenotypes for Alpha-Methylacetoacetic Aciduria

Symptoms via clinical synopsis from OMIM:

53
AbdomenGastrointestinal:
vomiting

MetabolicFeatures:
ketoacidosis, episodic
dehydration

NeurologicCentralNervousSystem:
mental retardation (in some cases)

LaboratoryAbnormalities:
increased urinary 2-methyl-3-hydroxybutyric acid
increased urinary 2-methylacetoacetic acid
increased urinary tiglylglycine
increased urinary 2-butanone


Clinical features from OMIM:

203750

Human phenotypes related to Alpha-Methylacetoacetic Aciduria:

31
# Description HPO Frequency HPO Source Accession
1 intellectual disability 31 HP:0001249
2 dehydration 31 HP:0001944
3 vomiting 31 HP:0002013
4 episodic ketoacidosis 31 HP:0005974

UMLS symptoms related to Alpha-Methylacetoacetic Aciduria:


vomiting

Drugs & Therapeutics for Alpha-Methylacetoacetic Aciduria

Search Clinical Trials , NIH Clinical Center for Alpha-Methylacetoacetic Aciduria

Cochrane evidence based reviews: pseudo-zellweger syndrome

Genetic Tests for Alpha-Methylacetoacetic Aciduria

Anatomical Context for Alpha-Methylacetoacetic Aciduria

Publications for Alpha-Methylacetoacetic Aciduria

Articles related to Alpha-Methylacetoacetic Aciduria:

(show all 30)
# Title Authors Year
1
Characterization and outcome of 41 patients with beta-ketothiolase deficiency: 10A years' experience of a medical center in northern Vietnam. ( 28220263 )
2017
2
Beta-Ketothiolase Deficiency Presenting with Metabolic Stroke After a Normal Newborn Screen in Two Individuals. ( 28726122 )
2017
3
[Analysis of clinical phenotype and ACAT1 gene mutation in a family affected with beta-ketothiolase deficiency]. ( 27264805 )
2016
4
Clinical and Mutational Characterizations of Ten Indian Patients with Beta-Ketothiolase Deficiency. ( 27928777 )
2016
5
NMR-based urinalysis for beta-ketothiolase deficiency. ( 25195009 )
2014
6
Metabolic encephalopathy in beta-ketothiolase deficiency: The first report from India. ( 23958592 )
2013
7
Beta-ketothiolase deficiency and pregnancy. ( 23664791 )
2013
8
A treatable new cause of chorea: beta-ketothiolase deficiency. ( 23818432 )
2013
9
MRI of Pallidal Involvement in Beta-Ketothiolase Deficiency. ( 23163837 )
2012
10
Three Japanese Patients with Beta-Ketothiolase Deficiency Who Share a Mutation, c.431A>C (H144P) in ACAT1 : Subtle Abnormality in Urinary Organic Acid Analysis and Blood Acylcarnitine Analysis Using Tandem Mass Spectrometry. ( 23430882 )
2012
11
Beta-ketothiolase deficiency brought with lethargy: case report. ( 21247997 )
2011
12
Enantioselective analysis of ketone bodies in patients with beta-ketothiolase deficiency, medium-chain acyl coenzyme A dehydrogenase deficiency and ketonemic vomiting. ( 10755375 )
2000
13
Mitochondrial acetoacetyl-CoA thiolase (beta-ketothiolase) deficiency and pregnancy. ( 9700610 )
1998
14
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
15
Molecular basis of Zellweger syndrome, beta-ketothiolase deficiency and mucopolysaccharidoses. ( 9183994 )
1997
16
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
17
Molecular basis of beta-ketothiolase deficiency: mutations and polymorphisms in the human mitochondrial acetoacetyl-coenzyme A thiolase gene. ( 7749408 )
1995
18
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
19
Induction of fetal hemoglobin in the presence of increased 3-hydroxybutyric acid associated with beta-ketothiolase deficiency. ( 7520129 )
1994
20
Beta-ketothiolase deficiency. A case report. ( 1509529 )
1992
21
beta-Ketothiolase deficiency with favourable evolution. ( 3126364 )
1987
22
Characterization of new diagnostic acylcarnitines in patients with beta-ketothiolase deficiency and glutaric aciduria type I using mass spectrometry. ( 3435793 )
1987
23
Two cases of beta-ketothiolase deficiency: a comparison. ( 6434866 )
1984
24
A case of beta-ketothiolase deficiency. ( 6422156 )
1983
25
The occurrence of substituted 3-methyl-3-hydroxyglutaric acids in urine in propionic acidaemia and in beta-ketothiolase deficiency. ( 6133567 )
1983
26
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
27
Beta-ketothiolase deficiency in a family confirmed by in vitro enzymatic assays in fibroblasts. ( 7173255 )
1982
28
Congestive cardiomyopathy associated with beta-ketothiolase deficiency. ( 7299555 )
1981
29
Beta-ketothiolase deficiency as a cause of the "ketotic hyperglycinemia syndrome". ( 4812006 )
1974
30
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

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

71
# Symbol AA change Variation ID SNP ID
1 ACAT1 p.Asn93Ser VAR_007498 rs120074145
2 ACAT1 p.Gly152Ala VAR_007499 rs762991875
3 ACAT1 p.Asn158Asp VAR_007500 rs148639841
4 ACAT1 p.Gly183Arg VAR_007501 rs120074141
5 ACAT1 p.Thr297Met VAR_007502 rs886041122
6 ACAT1 p.Ala301Pro VAR_007503
7 ACAT1 p.Ile312Thr VAR_007504 rs120074146
8 ACAT1 p.Ala333Pro VAR_007505 rs120074147
9 ACAT1 p.Gly379Val VAR_007506 rs120074143
10 ACAT1 p.Ala380Thr VAR_007507 rs120074140

ClinVar genetic disease variations for Alpha-Methylacetoacetic Aciduria:

6 (show all 26)
# Gene Variation Type Significance SNP ID Assembly Location
1 ACAT1 NM_000019.3(ACAT1): c.472A> G (p.Asn158Asp) single nucleotide variant Pathogenic rs148639841 GRCh37 Chromosome 11, 108009661: 108009661
2 ACAT1 NM_000019.3(ACAT1): c.730+2T> C single nucleotide variant Pathogenic rs398123096 GRCh37 Chromosome 11, 108010944: 108010944
3 ACAT1 NM_000019.3(ACAT1): c.905delA (p.Lys302Argfs) deletion Pathogenic rs398123097 GRCh37 Chromosome 11, 108013242: 108013242
4 ACAT1 NM_000019.3(ACAT1): c.444_445delGG (p.Met148Ilefs) deletion Pathogenic rs727503795 GRCh37 Chromosome 11, 108009633: 108009634
5 ACAT1 NM_000019.3(ACAT1): c.826+1G> T single nucleotide variant Pathogenic rs727503796 GRCh37 Chromosome 11, 108012428: 108012428
6 ACAT1 NM_000019.3(ACAT1): c.1006-4_1006-1delinsAAA indel Pathogenic rs797044633 GRCh37 Chromosome 11, 108016925: 108016928
7 ACAT1 NM_000019.3(ACAT1): c.203G> T (p.Gly68Val) single nucleotide variant Likely pathogenic rs794727475 GRCh37 Chromosome 11, 108004629: 108004629
8 ACAT1 NM_000019.3(ACAT1): c.455G> C (p.Gly152Ala) single nucleotide variant Likely pathogenic rs762991875 GRCh37 Chromosome 11, 108009644: 108009644
9 ACAT1 NM_000019.3(ACAT1): c.473A> G (p.Asn158Ser) single nucleotide variant Pathogenic rs199524907 GRCh37 Chromosome 11, 108009662: 108009662
10 ACAT1 NM_000019.3(ACAT1): c.1138G> A (p.Ala380Thr) single nucleotide variant Pathogenic rs120074140 GRCh37 Chromosome 11, 108017061: 108017061
11 ACAT1 NM_000019.3(ACAT1): c.547G> A (p.Gly183Arg) single nucleotide variant Pathogenic rs120074141 GRCh37 Chromosome 11, 108009736: 108009736
12 ACAT1 NM_000019.3(ACAT1): c.1006-2A> C single nucleotide variant Pathogenic rs145229472 GRCh38 Chromosome 11, 108146200: 108146200
13 ACAT1 NM_000019.3(ACAT1): c.1163+2T> C single nucleotide variant Pathogenic GRCh38 Chromosome 11, 108146361: 108146361
14 ACAT1 NM_000019.3(ACAT1): c.2T> A (p.Met1Lys) single nucleotide variant Pathogenic rs120074142 GRCh37 Chromosome 11, 107992335: 107992335
15 ACAT1 NM_000019.3(ACAT1): c.1136G> T (p.Gly379Val) single nucleotide variant Pathogenic rs120074143 GRCh37 Chromosome 11, 108017059: 108017059
16 ACAT1 NM_000019.3(ACAT1): c.814C> T (p.Gln272Ter) single nucleotide variant Pathogenic rs120074144 GRCh37 Chromosome 11, 108012415: 108012415
17 ACAT1 NM_000019.3(ACAT1): c.1033_1035delGAA (p.Glu345del) deletion Pathogenic rs387906282 GRCh37 Chromosome 11, 108016956: 108016958
18 ACAT1 NM_000019.3(ACAT1): c.1083dupA (p.Ala362Serfs) duplication Pathogenic rs387906283 GRCh37 Chromosome 11, 108017006: 108017006
19 ACAT1 NM_000019.3(ACAT1): c.278A> G (p.Asn93Ser) single nucleotide variant Pathogenic rs120074145 GRCh37 Chromosome 11, 108004987: 108004987
20 ACAT1 NM_000019.3(ACAT1): c.935T> C (p.Ile312Thr) single nucleotide variant Pathogenic rs120074146 GRCh37 Chromosome 11, 108013272: 108013272
21 ACAT1 NM_000019.3(ACAT1): c.997G> C (p.Ala333Pro) single nucleotide variant Pathogenic rs120074147 GRCh37 Chromosome 11, 108014766: 108014766
22 ACAT1 NM_000019.3(ACAT1): c.433C> G (p.Gln145Glu) single nucleotide variant Pathogenic rs120074148 GRCh37 Chromosome 11, 108005967: 108005967
23 ACAT1 NM_000019.3(ACAT1): c.149delC (p.Thr50Asnfs) deletion Pathogenic rs779565865 GRCh37 Chromosome 11, 108004575: 108004575
24 ACAT1 NM_000019.3(ACAT1): c.653C> T (p.Ser218Phe) single nucleotide variant Likely pathogenic rs879255505 GRCh38 Chromosome 11, 108140138: 108140138
25 ACAT1 NM_000019.3(ACAT1): c.1006-1G> C single nucleotide variant Pathogenic rs1131691567 GRCh37 Chromosome 11, 108016928: 108016928
26 ACAT1 NM_000019.3(ACAT1): c.1199A> G (p.His400Arg) single nucleotide variant Likely pathogenic rs761086326 GRCh38 Chromosome 11, 108147305: 108147305

Expression for Alpha-Methylacetoacetic Aciduria

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

Pathways for Alpha-Methylacetoacetic Aciduria

Pathways related to Alpha-Methylacetoacetic Aciduria according to KEGG:

36
# Name Kegg Source Accession
1 Valine, leucine and isoleucine degradation hsa00280
2 Synthesis and degradation of ketone bodies hsa00072

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

# Super pathways Score Top Affiliating Genes
1
Show member pathways
13.36 ACAA1 ACAD8 ACADSB ACAT1 HSD17B10 MAT1A
2
Show member pathways
13.17 ACAD8 ACADSB ACAT1 HSD17B10 MAT1A
3
Show member pathways
11.65 ACAT1 HSD17B10
4
Show member pathways
11.1 ACAA1 ACADSB ACAT1
5
Show member pathways
11.09 ACAA1 ACAD8 ACADSB ACAT1 HSD17B10
6
Show member pathways
11.05 ACAA1 HSD17B10
7 10.27 ACADSB HSD17B10

GO Terms for Alpha-Methylacetoacetic Aciduria

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

# Name GO ID Score Top Affiliating Genes
1 mitochondrion GO:0005739 9.26 ACAD8 ACADSB ACAT1 HSD17B10
2 mitochondrial matrix GO:0005759 8.92 ACAD8 ACADSB ACAT1 HSD17B10

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

# Name GO ID Score Top Affiliating Genes
1 oxidation-reduction process GO:0055114 9.54 ACAD8 ACADSB HSD17B10
2 lipid metabolic process GO:0006629 9.46 ACAA1 ACAD8 ACADSB HSD17B10
3 fatty acid metabolic process GO:0006631 9.4 ACAA1 ACADSB
4 protein homotetramerization GO:0051289 9.32 HSD17B10 MAT1A
5 fatty acid beta-oxidation GO:0006635 9.26 ACAA1 ACAT1
6 metabolic process GO:0008152 9.26 ACAA1 ACAD8 ACADSB ACAT1
7 branched-chain amino acid catabolic process GO:0009083 8.92 ACAD8 ACADSB ACAT1 HSD17B10

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

# Name GO ID Score Top Affiliating Genes
1 oxidoreductase activity GO:0016491 9.5 ACAD8 ACADSB HSD17B10
2 transferase activity, transferring acyl groups GO:0016746 9.37 ACAA1 ACAT1
3 flavin adenine dinucleotide binding GO:0050660 9.26 ACAD8 ACADSB
4 oxidoreductase activity, acting on the CH-CH group of donors GO:0016627 9.16 ACAD8 ACADSB
5 transferase activity, transferring acyl groups other than amino-acyl groups GO:0016747 8.96 ACAA1 ACAT1
6 acyl-CoA dehydrogenase activity GO:0003995 8.62 ACAD8 ACADSB

Sources for Alpha-Methylacetoacetic Aciduria

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
16 ExPASy
18 FMA
27 GO
28 GTR
29 HGMD
30 HMDB
31 HPO
32 ICD10
33 ICD10 via Orphanet
34 ICD9CM
35 IUPHAR
36 KEGG
37 LifeMap
39 MedGen
41 MeSH
42 MESH via Orphanet
43 MGI
45 NCI
46 NCIt
47 NDF-RT
50 NINDS
51 Novoseek
53 OMIM
54 OMIM via Orphanet
58 PubMed
60 QIAGEN
65 SNOMED-CT via HPO
66 SNOMED-CT via Orphanet
67 TGDB
68 Tocris
69 UMLS
70 UMLS via Orphanet
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