MCID: ALP011
MIFTS: 37

Alpha-Ketoglutarate Dehydrogenase Deficiency

Categories: Rare diseases, Neuronal diseases, Metabolic diseases

Aliases & Classifications for Alpha-Ketoglutarate Dehydrogenase Deficiency

MalaCards integrated aliases for Alpha-Ketoglutarate Dehydrogenase Deficiency:

Name: Alpha-Ketoglutarate Dehydrogenase Deficiency 53 49 55 28 13 69
Oxoglutaricaciduria 49 55
2 Alpha Ketoglutarate Dehydrogenase Deficiency 49
2-Ketoglutarate Dehydrogenase Deficiency 53
Alpha-Kgd Deficiency 53
Oxoglutaric Aciduria 53
Alpha Kgd Deficiency 49

Characteristics:

Orphanet epidemiological data:

55
oxoglutaricaciduria
Inheritance: Autosomal recessive; Age of onset: Neonatal; Age of death: early childhood;

OMIM:

53
Inheritance:
autosomal recessive


HPO:

31
alpha-ketoglutarate dehydrogenase deficiency:
Mortality/Aging death in childhood
Inheritance autosomal recessive inheritance


Classifications:



External Ids:

OMIM 53 203740
Orphanet 55 ORPHA31
MESH via Orphanet 42 C536582
UMLS via Orphanet 70 C2752074
ICD10 via Orphanet 33 E88.8
MedGen 39 C2752074
UMLS 69 C2752074

Summaries for Alpha-Ketoglutarate Dehydrogenase Deficiency

NIH Rare Diseases : 49 The following summary is from Orphanet, a European reference portal for information on rare diseases and orphan drugs.Orpha Number: 31Disease definitionOxoglutaric aciduria is a very rare tricarboxylic acid cycle disorder (see this term), resulting from a deficiency in alpha-ketoglutarate dehydrogenase (one of the three subunits of the alpha-ketoglutarate dehydrogenase complex), that most often presents in the neonatal period with hypotonia, severe encephalopathy, extrapyramidal signs, pyramidal tract dysfunction and seizures and that frequently results in death in early childhood. Metabolic acidosis, elevated lactate and glutamate levels and variable degrees of glutaric aciduria are noted. Sudden death, myocardiopathy, and hepatic disorders have also been reported in some cases.Visit the Orphanet disease page for more resources. Last updated: 11/12/2014

MalaCards based summary : Alpha-Ketoglutarate Dehydrogenase Deficiency, also known as oxoglutaricaciduria, is related to lactic acidosis and wernicke-korsakoff syndrome, and has symptoms including ataxia, hydrocephalus and global developmental delay. An important gene associated with Alpha-Ketoglutarate Dehydrogenase Deficiency is OGDH (Oxoglutarate Dehydrogenase), and among its related pathways/superpathways are Viral mRNA Translation and Respiratory electron transport, ATP synthesis by chemiosmotic coupling, and heat production by uncoupling proteins.. Affiliated tissues include salivary gland and skeletal muscle, and related phenotypes are Decreased shRNA abundance (Z-score < -2) and Decreased shRNA abundance (Z-score < -2)

Description 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:

# Related Disease Score Top Affiliating Genes
1 lactic acidosis 29.3 DLD PDHA1
2 wernicke-korsakoff syndrome 9.7 DLST OGDH
3 pyruvate dehydrogenase e3-binding protein deficiency 9.6 DLD PDHA1
4 primary biliary cirrhosis 9.6 DLD OGDH

Symptoms & Phenotypes for Alpha-Ketoglutarate Dehydrogenase Deficiency

Symptoms via clinical synopsis from OMIM:

53
Metabolic:
metabolic acidosis
congenital lactic acidosis

Lab:
hyperlactatemia
alpha-ketoglutarate dehydrogenase deficiency

Neuro:
hypotonia

Misc:
early childhood death


Clinical features from OMIM:

203740

Human phenotypes related to Alpha-Ketoglutarate Dehydrogenase Deficiency:

55 31 (show all 15)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 ataxia 55 31 hallmark (90%) Very frequent (99-80%) HP:0001251
2 hydrocephalus 55 31 frequent (33%) Frequent (79-30%) HP:0000238
3 global developmental delay 55 31 hallmark (90%) Very frequent (99-80%) HP:0001263
4 short stature 55 31 hallmark (90%) Very frequent (99-80%) HP:0004322
5 hypertonia 55 31 hallmark (90%) Very frequent (99-80%) HP:0001276
6 abnormality of movement 55 31 frequent (33%) Frequent (79-30%) HP:0100022
7 skeletal muscle atrophy 55 31 hallmark (90%) Very frequent (99-80%) HP:0003202
8 abnormality of krebs cycle metabolism 55 31 hallmark (90%) Very frequent (99-80%) HP:0000816
9 abnormal urine alpha-ketoglutarate concentration 55 31 hallmark (90%) Very frequent (99-80%) HP:0012401
10 increased serum lactate 31 HP:0002151
11 metabolic acidosis 31 HP:0001942
12 generalized hypotonia 31 HP:0001290
13 abnormality of the salivary glands 55 Frequent (79-30%)
14 congenital lactic acidosis 31 HP:0004902
15 abnormal salivary gland morphology 31 frequent (33%) HP:0010286

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

25
# Description GenomeRNAi Source Accession Score Top Affiliating Genes
1 Decreased shRNA abundance (Z-score < -2) GR00366-A-116 9.23 OGDH
2 Decreased shRNA abundance (Z-score < -2) GR00366-A-160 9.23 OGDH
3 Decreased shRNA abundance (Z-score < -2) GR00366-A-18 9.23 PDHA1
4 Decreased shRNA abundance (Z-score < -2) GR00366-A-191 9.23 PDHA1
5 Decreased shRNA abundance (Z-score < -2) GR00366-A-48 9.23 OGDH
6 Decreased shRNA abundance (Z-score < -2) GR00366-A-60 9.23 PDHA1
7 Decreased shRNA abundance (Z-score < -2) GR00366-A-68 9.23 OGDH PDHA1

MGI Mouse Phenotypes related to Alpha-Ketoglutarate Dehydrogenase Deficiency:

43
# Description MGI Source Accession Score Top Affiliating Genes
1 growth/size/body region MP:0005378 8.92 DLD DLST OGDH 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 Alpha-Ketoglutarate Dehydrogenase Deficiency 28 OGDH

Anatomical Context for Alpha-Ketoglutarate Dehydrogenase Deficiency

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

38
Salivary Gland, Skeletal Muscle

Publications for Alpha-Ketoglutarate Dehydrogenase Deficiency

Articles related to Alpha-Ketoglutarate Dehydrogenase Deficiency:

# Title Authors Year
1
A novel mutation in the dihydrolipoamide dehydrogenase E3 subunit gene (DLD) resulting in an atypical form of alpha-ketoglutarate dehydrogenase deficiency. ( 15712224 )
2005
2
Alpha-ketoglutarate dehydrogenase deficiency presenting as congenital lactic acidosis. ( 1640293 )
1992

Variations for Alpha-Ketoglutarate Dehydrogenase Deficiency

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 11)
# Super pathways Score Top Affiliating Genes
1
Show member pathways
13.2 DLD DLST OGDH PDHA1
2
Show member pathways
12.93 DLD DLST OGDH PDHA1
3
Show member pathways
11.94 DLD DLST OGDH PDHA1
4
Show member pathways
11.68 DLD DLST OGDH PDHA1
5
Show member pathways
11.63 DLD DLST OGDH
6
Show member pathways
11.47 DLD DLST OGDH PDHA1
7
Show member pathways
11.3 DLD PDHA1
8 11.23 DLST OGDH
9 11.22 DLD DLST OGDH PDHA1
10
Show member pathways
11.03 DLD PDHA1
11
Show member pathways
10.54 DLD DLST OGDH PDHA1

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 9.62 DLD DLST OGDH PDHA1
2 myelin sheath GO:0043209 9.43 DLD DLST PDHA1
3 mitochondrial matrix GO:0005759 9.26 DLD DLST OGDH PDHA1
4 pyruvate dehydrogenase complex GO:0045254 9.16 DLD PDHA1
5 oxoglutarate dehydrogenase complex GO:0045252 8.8 DLD DLST OGDH

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

(show all 11)
# Name GO ID Score Top Affiliating Genes
1 oxidation-reduction process GO:0055114 9.67 DLD OGDH PDHA1
2 metabolic process GO:0008152 9.65 DLST OGDH PDHA1
3 generation of precursor metabolites and energy GO:0006091 9.46 DLST OGDH
4 pyruvate metabolic process GO:0006090 9.43 DLD PDHA1
5 2-oxoglutarate metabolic process GO:0006103 9.4 DLD OGDH
6 regulation of acetyl-CoA biosynthetic process from pyruvate GO:0010510 9.37 DLD PDHA1
7 lysine catabolic process GO:0006554 9.33 DLD DLST OGDH
8 mitochondrial acetyl-CoA biosynthetic process from pyruvate GO:0061732 9.32 DLD PDHA1
9 acetyl-CoA biosynthetic process from pyruvate GO:0006086 9.26 DLD PDHA1
10 tricarboxylic acid cycle GO:0006099 9.26 DLD DLST OGDH PDHA1
11 cellular nitrogen compound metabolic process GO:0034641 8.92 DLD DLST OGDH PDHA1

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 DLD OGDH PDHA1
2 oxidoreductase activity, acting on the aldehyde or oxo group of donors, disulfide as acceptor GO:0016624 8.96 OGDH PDHA1
3 pyruvate dehydrogenase (NAD+) activity GO:0034604 8.62 DLD PDHA1

Sources for Alpha-Ketoglutarate Dehydrogenase Deficiency

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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