MCID: ALP011
MIFTS: 39

Alpha-Ketoglutarate Dehydrogenase Deficiency

Categories: Metabolic diseases, Neuronal diseases, Rare diseases

Aliases & Classifications for Alpha-Ketoglutarate Dehydrogenase Deficiency

MalaCards integrated aliases for Alpha-Ketoglutarate Dehydrogenase Deficiency:

Name: Alpha-Ketoglutarate Dehydrogenase Deficiency 57 20 58 13 39 70
Oxoglutaricaciduria 20 29 6
Oxoglutaric Aciduria 57 58
2 Alpha Ketoglutarate Dehydrogenase Deficiency 20
2-Ketoglutarate Dehydrogenase Deficiency 57
Alpha-Kgd Deficiency 57
Alpha Kgd Deficiency 20

Characteristics:

Orphanet epidemiological data:

58
oxoglutaric aciduria
Inheritance: Autosomal recessive; Age of onset: Neonatal; Age of death: early childhood;

OMIM®:

57 (Updated 05-Apr-2021)
Inheritance:
autosomal recessive


HPO:

31
alpha-ketoglutarate dehydrogenase deficiency:
Inheritance autosomal recessive inheritance
Onset and clinical course death in childhood


Classifications:

Orphanet: 58  
Rare neurological diseases
Inborn errors of metabolism


External Ids:

OMIM® 57 203740
MESH via Orphanet 45 C536582
ICD10 via Orphanet 33 E88.8
UMLS via Orphanet 71 C2752074
Orphanet 58 ORPHA31
MedGen 41 C2752074
UMLS 70 C2752074

Summaries for Alpha-Ketoglutarate Dehydrogenase Deficiency

GARD : 20 The following summary is from Orphanet, a European reference portal for information on rare diseases and orphan drugs. Orpha Number: 31 Definition A rare, genetic, inborn error of metabolism disorder characterized by neonatal-onset of developmental delay, hypotonia, hepatomegaly, lactic acidemia, increased creatine kinase levels, elevated alpha-ketoglutaric acid in urine, and a decreased plasma beta-hydroxybutyrate-to-acetoacetate ratio. Pyruvate dehydrogenase deficiency can be associated, leading to hypoglycemia and neurologic anomalies, including seizures.

MalaCards based summary : Alpha-Ketoglutarate Dehydrogenase Deficiency, also known as oxoglutaricaciduria, is related to pyruvate dehydrogenase e1-alpha deficiency and lactic acidosis. An important gene associated with Alpha-Ketoglutarate Dehydrogenase Deficiency is OGDH (Oxoglutarate Dehydrogenase), and among its related pathways/superpathways are Metabolism and Viral mRNA Translation. Affiliated tissues include skeletal muscle and salivary gland, and related phenotypes are ataxia and global developmental delay

More information from OMIM: 203740

Related Diseases for Alpha-Ketoglutarate Dehydrogenase Deficiency

Diseases related to Alpha-Ketoglutarate Dehydrogenase Deficiency via text searches within MalaCards or GeneCards Suite gene sharing:

(show all 17)
# Related Disease Score Top Affiliating Genes
1 pyruvate dehydrogenase e1-alpha deficiency 30.0 PDHA1 DLD
2 lactic acidosis 29.4 PDHA1 OGDH DLD
3 tricarboxylic acid cycle, defect of 11.3
4 dihydrolipoamide dehydrogenase deficiency 10.2
5 autosomal recessive disease 10.1
6 metabolic acidosis 10.1
7 hypotonia 10.1
8 bacteriuria 10.1
9 cerebral palsy 10.1
10 tremor 10.1
11 neurometabolic disease 10.1
12 microcephaly, amish type 10.1
13 hypertonia 10.1
14 pyruvate dehydrogenase e3-binding protein deficiency 9.9 PDHA1 DLD
15 wernicke-korsakoff syndrome 9.6 OGDH DLST
16 primary biliary cholangitis 9.6 OGDH DLD
17 maple syrup urine disease 9.4 OGDH DLST DLD

Graphical network of the top 20 diseases related to Alpha-Ketoglutarate Dehydrogenase Deficiency:



Diseases related to Alpha-Ketoglutarate Dehydrogenase Deficiency

Symptoms & Phenotypes for Alpha-Ketoglutarate Dehydrogenase Deficiency

Human phenotypes related to Alpha-Ketoglutarate Dehydrogenase Deficiency:

58 31 (show all 15)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 ataxia 58 31 hallmark (90%) Very frequent (99-80%) HP:0001251
2 global developmental delay 58 31 hallmark (90%) Very frequent (99-80%) HP:0001263
3 short stature 58 31 hallmark (90%) Very frequent (99-80%) HP:0004322
4 hypertonia 58 31 hallmark (90%) Very frequent (99-80%) HP:0001276
5 skeletal muscle atrophy 58 31 hallmark (90%) Very frequent (99-80%) HP:0003202
6 abnormality of krebs cycle metabolism 58 31 hallmark (90%) Very frequent (99-80%) HP:0000816
7 abnormal urine alpha-ketoglutarate concentration 58 31 hallmark (90%) Very frequent (99-80%) HP:0012401
8 hydrocephalus 58 31 frequent (33%) Frequent (79-30%) HP:0000238
9 abnormality of movement 58 31 frequent (33%) Frequent (79-30%) HP:0100022
10 abnormal salivary gland morphology 58 31 frequent (33%) Frequent (79-30%) HP:0010286
11 increased serum lactate 31 HP:0002151
12 metabolic acidosis 31 HP:0001942
13 generalized hypotonia 31 HP:0001290
14 congenital lactic acidosis 31 HP:0004902
15 hypotonia 31 HP:0001252

Symptoms via clinical synopsis from OMIM®:

57 (Updated 05-Apr-2021)
Metabolic:
metabolic acidosis
congenital lactic acidosis

Lab:
hyperlactatemia
alpha-ketoglutarate dehydrogenase deficiency

Neuro:
hypotonia

Misc:
early childhood death

Clinical features from OMIM®:

203740 (Updated 05-Apr-2021)

GenomeRNAi Phenotypes related to Alpha-Ketoglutarate Dehydrogenase Deficiency according to GeneCards Suite gene sharing:

26 (show all 15)
# Description GenomeRNAi Source Accession Score Top Affiliating Genes
1 Decreased shRNA abundance (Z-score < -2) GR00366-A-100 9.43 OGDH
2 Decreased shRNA abundance (Z-score < -2) GR00366-A-11 9.43 OGDH
3 Decreased shRNA abundance (Z-score < -2) GR00366-A-116 9.43 OGDH
4 Decreased shRNA abundance (Z-score < -2) GR00366-A-122 9.43 PDHA1
5 Decreased shRNA abundance (Z-score < -2) GR00366-A-60 9.43 PDHA1
6 Decreased shRNA abundance (Z-score < -2) GR00366-A-79 9.43 OGDH
7 Increased shRNA abundance (Z-score > 2) GR00366-A-137 9.28 PDHA1
8 Increased shRNA abundance (Z-score > 2) GR00366-A-153 9.28 DLST
9 Increased shRNA abundance (Z-score > 2) GR00366-A-16 9.28 PDHA1
10 Increased shRNA abundance (Z-score > 2) GR00366-A-166 9.28 PDHA1
11 Increased shRNA abundance (Z-score > 2) GR00366-A-18 9.28 PDHA1
12 Increased shRNA abundance (Z-score > 2) GR00366-A-191 9.28 PDHA1
13 Increased shRNA abundance (Z-score > 2) GR00366-A-20 9.28 DLST
14 Increased shRNA abundance (Z-score > 2) GR00366-A-42 9.28 PDHA1
15 Increased shRNA abundance (Z-score > 2) GR00366-A-68 9.28 PDHA1

Drugs & Therapeutics for Alpha-Ketoglutarate Dehydrogenase Deficiency

Search Clinical Trials , NIH Clinical Center for Alpha-Ketoglutarate Dehydrogenase Deficiency

Genetic Tests for Alpha-Ketoglutarate Dehydrogenase Deficiency

Genetic tests related to Alpha-Ketoglutarate Dehydrogenase Deficiency:

# Genetic test Affiliating Genes
1 Oxoglutaricaciduria 29 OGDH

Anatomical Context for Alpha-Ketoglutarate Dehydrogenase Deficiency

MalaCards organs/tissues related to Alpha-Ketoglutarate Dehydrogenase Deficiency:

40
Skeletal Muscle, Salivary Gland

Publications for Alpha-Ketoglutarate Dehydrogenase Deficiency

Articles related to Alpha-Ketoglutarate Dehydrogenase Deficiency:

# Title Authors PMID Year
1
2-Ketoglutarate dehydrogenase deficiency, a rare cause of primary hyperlactataemia: report of a new case. 57
8295396 1993
2
A familial progressive neurodegenerative disease with 2-oxoglutaric aciduria. 57
7075624 1982
3
Dysmorphic Features, Frontal Cerebral Cavernoma, and Hyperglycemia in a Girl with a De Novo Deletion of 7.23 Mb in Region 7p13-p12.1. 61
28387648 2017
4
A novel mutation in the dihydrolipoamide dehydrogenase E3 subunit gene (DLD) resulting in an atypical form of alpha-ketoglutarate dehydrogenase deficiency. 61
15712224 2005
5
[Alpha-ketoglutarate dehydrogenase deficiency]. 61
12013995 2002
6
[Alpha ketoglutarate dehydrogenase deficiency]. 61
11596338 2001
7
The expanding clinical spectrum of mitochondrial diseases. 61
8338207 1993
8
Alpha-ketoglutarate dehydrogenase deficiency presenting as congenital lactic acidosis. 61
1640293 1992

Variations for Alpha-Ketoglutarate Dehydrogenase Deficiency

ClinVar genetic disease variations for Alpha-Ketoglutarate Dehydrogenase Deficiency:

6 (show all 19)
# Gene Name Type Significance ClinVarId dbSNP ID Position
1 OGDH NM_002541.4(OGDH):c.1844C>T (p.Thr615Ile) SNV Uncertain significance 471072 rs773035937 GRCh37: 7:44736100-44736100
GRCh38: 7:44696501-44696501
2 OGDH NM_002541.4(OGDH):c.2776G>A (p.Ala926Thr) SNV Uncertain significance 653756 rs1210479704 GRCh37: 7:44746967-44746967
GRCh38: 7:44707368-44707368
3 OGDH NM_002541.4(OGDH):c.1829C>T (p.Thr610Met) SNV Uncertain significance 665016 rs746947310 GRCh37: 7:44736085-44736085
GRCh38: 7:44696486-44696486
4 OGDH NM_002541.4(OGDH):c.622C>T (p.Arg208Cys) SNV Uncertain significance 937040 GRCh37: 7:44706439-44706439
GRCh38: 7:44666840-44666840
5 OGDH NM_002541.4(OGDH):c.904G>C (p.Val302Leu) SNV Uncertain significance 943397 GRCh37: 7:44714125-44714125
GRCh38: 7:44674526-44674526
6 OGDH NM_002541.4(OGDH):c.2126A>G (p.Asn709Ser) SNV Uncertain significance 1020921 GRCh37: 7:44737043-44737043
GRCh38: 7:44697444-44697444
7 OGDH NM_002541.4(OGDH):c.2422G>A (p.Val808Ile) SNV Uncertain significance 1029459 GRCh37: 7:44737854-44737854
GRCh38: 7:44698255-44698255
8 OGDH NM_002541.4(OGDH):c.2904C>T (p.Tyr968=) SNV Likely benign 735209 rs546154454 GRCh37: 7:44747288-44747288
GRCh38: 7:44707689-44707689
9 OGDH NM_002541.4(OGDH):c.2458A>T (p.Asn820Tyr) SNV Likely benign 770374 rs151001666 GRCh37: 7:44739767-44739767
GRCh38: 7:44700168-44700168
10 OGDH NM_002541.4(OGDH):c.164C>T (p.Ser55Leu) SNV Benign 780042 rs2230445 GRCh37: 7:44664106-44664106
GRCh38: 7:44624507-44624507
11 OGDH NM_002541.4(OGDH):c.1857T>C (p.Asn619=) SNV Benign 785215 rs113823811 GRCh37: 7:44736113-44736113
GRCh38: 7:44696514-44696514
12 OGDH NM_002541.4(OGDH):c.1188C>T (p.Gly396=) SNV Benign 791078 rs147519663 GRCh37: 7:44715730-44715730
GRCh38: 7:44676131-44676131
13 OGDH NM_002541.4(OGDH):c.2784A>G (p.Thr928=) SNV Benign 559272 rs112309751 GRCh37: 7:44746975-44746975
GRCh38: 7:44707376-44707376
14 OGDH NM_002541.4(OGDH):c.39A>C (p.Pro13=) SNV Benign 559267 rs34777281 GRCh37: 7:44663981-44663981
GRCh38: 7:44624382-44624382
15 OGDH NM_002541.4(OGDH):c.3042C>T (p.Phe1014=) SNV Benign 714606 rs144300328 GRCh37: 7:44747568-44747568
GRCh38: 7:44707969-44707969
16 OGDH NM_002541.4(OGDH):c.357C>T (p.Asn119=) SNV Benign 721829 rs116191385 GRCh37: 7:44685060-44685060
GRCh38: 7:44645461-44645461
17 OGDH NM_002541.4(OGDH):c.1422C>T (p.His474=) SNV Benign 725200 rs79522383 GRCh37: 7:44733510-44733510
GRCh38: 7:44693911-44693911
18 OGDH NM_002541.4(OGDH):c.222+9C>T SNV Benign 744747 rs201280081 GRCh37: 7:44664173-44664173
GRCh38: 7:44624574-44624574
19 OGDH NM_002541.4(OGDH):c.1968G>A (p.Ala656=) SNV Benign 786390 rs61756582 GRCh37: 7:44736580-44736580
GRCh38: 7:44696981-44696981

Expression for Alpha-Ketoglutarate Dehydrogenase Deficiency

Search GEO for disease gene expression data for Alpha-Ketoglutarate Dehydrogenase Deficiency.

Pathways for Alpha-Ketoglutarate Dehydrogenase Deficiency

Pathways related to Alpha-Ketoglutarate Dehydrogenase Deficiency according to GeneCards Suite gene sharing:

(show all 13)
# Super pathways Score Top Affiliating Genes
1
Show member pathways
13.48 PDHA1 OGDH DLST DLD
2
Show member pathways
13.24 PDHA1 OGDH DLST DLD
3
Show member pathways
12.87 PDHA1 OGDH DLST DLD
4 12 PDHA1 DLST
5
Show member pathways
11.95 PDHA1 OGDH DLST DLD
6
Show member pathways
11.68 PDHA1 OGDH DLST DLD
7
Show member pathways
11.67 OGDH DLST DLD
8
Show member pathways
11.51 OGDH DLST DLD
9
Show member pathways
11.47 PDHA1 OGDH DLST DLD
10
Show member pathways
11.3 PDHA1 DLD
11 11.26 DLST DLD
12 11.22 PDHA1 OGDH DLST DLD
13
Show member pathways
10.47 PDHA1 OGDH DLST DLD

GO Terms for Alpha-Ketoglutarate Dehydrogenase Deficiency

Cellular components related to Alpha-Ketoglutarate Dehydrogenase Deficiency according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 mitochondrion GO:0005739 9.56 PDHA1 OGDH DLST DLD
2 mitochondrial matrix GO:0005759 9.26 PDHA1 OGDH DLST DLD
3 pyruvate dehydrogenase complex GO:0045254 9.16 PDHA1 DLD
4 oxoglutarate dehydrogenase complex GO:0045252 8.8 OGDH DLST DLD

Biological processes related to Alpha-Ketoglutarate Dehydrogenase Deficiency according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 oxidation-reduction process GO:0055114 9.65 PDHA1 OGDH DLD
2 generation of precursor metabolites and energy GO:0006091 9.46 OGDH DLST
3 pyruvate metabolic process GO:0006090 9.43 PDHA1 DLD
4 2-oxoglutarate metabolic process GO:0006103 9.43 OGDH DLST DLD
5 mitochondrial acetyl-CoA biosynthetic process from pyruvate GO:0061732 9.4 PDHA1 DLD
6 succinyl-CoA metabolic process GO:0006104 9.37 OGDH DLST
7 lysine catabolic process GO:0006554 9.33 OGDH DLST DLD
8 acetyl-CoA biosynthetic process from pyruvate GO:0006086 9.32 PDHA1 DLD
9 histone succinylation GO:0106077 9.13 OGDH DLST DLD
10 tricarboxylic acid cycle GO:0006099 8.92 PDHA1 OGDH DLST DLD

Molecular functions related to Alpha-Ketoglutarate Dehydrogenase Deficiency according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 oxidoreductase activity GO:0016491 9.33 PDHA1 OGDH DLD
2 oxidoreductase activity, acting on the aldehyde or oxo group of donors, disulfide as acceptor GO:0016624 8.96 PDHA1 OGDH
3 pyruvate dehydrogenase (NAD+) activity GO:0034604 8.62 PDHA1 DLD

Sources for Alpha-Ketoglutarate Dehydrogenase Deficiency

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 EFO
18 ExPASy
19 FMA
20 GARD
28 GO
29 GTR
30 HMDB
31 HPO
32 ICD10
33 ICD10 via Orphanet
34 ICD9CM
35 IUPHAR
36 KEGG
37 LifeMap
39 LOVD
41 MedGen
44 MeSH
45 MESH via Orphanet
46 MGI
49 NCI
50 NCIt
51 NDF-RT
53 NINDS
54 Novoseek
56 OMIM via Orphanet
57 OMIM® (Updated 05-Apr-2021)
61 PubMed
63 QIAGEN
68 SNOMED-CT via HPO
69 Tocris
70 UMLS
71 UMLS via Orphanet
Content
Loading form....