MCID: ALP011
MIFTS: 36

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 57 53 59 29 13 6 40 73
Oxoglutaricaciduria 53 59
2 Alpha Ketoglutarate Dehydrogenase Deficiency 53
2-Ketoglutarate Dehydrogenase Deficiency 57
Alpha-Kgd Deficiency 57
Oxoglutaric Aciduria 57
Alpha Kgd Deficiency 53

Characteristics:

Orphanet epidemiological data:

59
oxoglutaricaciduria
Inheritance: Autosomal recessive; Age of onset: Neonatal; Age of death: early childhood;

OMIM:

57
Inheritance:
autosomal recessive


HPO:

32
alpha-ketoglutarate dehydrogenase deficiency:
Mortality/Aging death in childhood
Inheritance autosomal recessive inheritance


Classifications:



External Ids:

OMIM 57 203740
Orphanet 59 ORPHA31
MESH via Orphanet 45 C536582
UMLS via Orphanet 74 C2752074
ICD10 via Orphanet 34 E88.8
MedGen 42 C2752074
UMLS 73 C2752074

Summaries for Alpha-Ketoglutarate Dehydrogenase Deficiency

NIH Rare Diseases : 53 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.

MalaCards based summary : Alpha-Ketoglutarate Dehydrogenase Deficiency, also known as oxoglutaricaciduria, is related to lactic acidosis and wernicke-korsakoff syndrome. 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 hydrocephalus and abnormality of krebs cycle metabolism

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 28.5 DLD PDHA1
2 wernicke-korsakoff syndrome 9.6 DLST OGDH
3 maple syrup urine disease 9.6 DLD OGDH
4 pyruvate dehydrogenase e3-binding protein deficiency 9.4 DLD PDHA1

Symptoms & Phenotypes for Alpha-Ketoglutarate Dehydrogenase Deficiency

Symptoms via clinical synopsis from OMIM:

57
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:

59 32 (show all 16)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 hydrocephalus 59 32 frequent (33%) Frequent (79-30%) HP:0000238
2 abnormality of krebs cycle metabolism 59 32 hallmark (90%) Very frequent (99-80%) HP:0000816
3 ataxia 59 32 hallmark (90%) Very frequent (99-80%) HP:0001251
4 global developmental delay 59 32 hallmark (90%) Very frequent (99-80%) HP:0001263
5 hypertonia 59 32 hallmark (90%) Very frequent (99-80%) HP:0001276
6 skeletal muscle atrophy 59 32 hallmark (90%) Very frequent (99-80%) HP:0003202
7 short stature 59 32 hallmark (90%) Very frequent (99-80%) HP:0004322
8 abnormal urine alpha-ketoglutarate concentration 59 32 hallmark (90%) Very frequent (99-80%) HP:0012401
9 abnormality of movement 59 32 frequent (33%) Frequent (79-30%) HP:0100022
10 abnormality of the salivary glands 59 Frequent (79-30%)
11 muscular hypotonia 32 HP:0001252
12 generalized hypotonia 32 HP:0001290
13 metabolic acidosis 32 HP:0001942
14 increased serum lactate 32 HP:0002151
15 congenital lactic acidosis 32 HP:0004902
16 abnormal salivary gland morphology 32 frequent (33%) HP:0010286

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

26
# Description GenomeRNAi Source Accession Score Top Affiliating Genes
1 Decreased shRNA abundance (Z-score < -2) GR00366-A-160 9.17 OGDH
2 Decreased shRNA abundance (Z-score < -2) GR00366-A-18 9.17 PDHA1
3 Decreased shRNA abundance (Z-score < -2) GR00366-A-191 9.17 PDHA1
4 Decreased shRNA abundance (Z-score < -2) GR00366-A-48 9.17 OGDH
5 Decreased shRNA abundance (Z-score < -2) GR00366-A-60 9.17 PDHA1
6 Decreased shRNA abundance (Z-score < -2) GR00366-A-68 9.17 PDHA1 OGDH

MGI Mouse Phenotypes related to Alpha-Ketoglutarate Dehydrogenase Deficiency:

46
# Description MGI Source Accession Score Top Affiliating Genes
1 growth/size/body region MP:0005378 8.92 OGDH PDHA1 DLD DLST

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 29 OGDH

Anatomical Context for Alpha-Ketoglutarate Dehydrogenase Deficiency

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

41
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

ClinVar genetic disease variations for Alpha-Ketoglutarate Dehydrogenase Deficiency:

6
# Gene Variation Type Significance SNP ID Assembly Location
1 OGDH NM_002541.3(OGDH): c.1844C> T (p.Thr615Ile) single nucleotide variant Uncertain significance rs773035937 GRCh37 Chromosome 7, 44736100: 44736100
2 OGDH NM_002541.3(OGDH): c.1844C> T (p.Thr615Ile) single nucleotide variant Uncertain significance rs773035937 GRCh38 Chromosome 7, 44696501: 44696501

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
12.99 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 13)
# Name GO ID Score Top Affiliating Genes
1 oxidation-reduction process GO:0055114 9.7 DLD OGDH PDHA1
2 metabolic process GO:0008152 9.69 DLST OGDH PDHA1
3 2-oxoglutarate metabolic process GO:0006103 9.5 DLD DLST OGDH
4 generation of precursor metabolites and energy GO:0006091 9.49 DLST OGDH
5 pyruvate metabolic process GO:0006090 9.48 DLD PDHA1
6 regulation of acetyl-CoA biosynthetic process from pyruvate GO:0010510 9.46 DLD PDHA1
7 mitochondrial acetyl-CoA biosynthetic process from pyruvate GO:0061732 9.43 DLD PDHA1
8 lysine catabolic process GO:0006554 9.43 DLD DLST OGDH
9 succinyl-CoA metabolic process GO:0006104 9.4 DLST OGDH
10 acetyl-CoA biosynthetic process from pyruvate GO:0006086 9.37 DLD PDHA1
11 histone succinylation GO:0106077 9.33 DLD DLST OGDH
12 tricarboxylic acid cycle GO:0006099 9.26 DLD DLST OGDH PDHA1
13 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
17 ExPASy
19 FMA
28 GO
29 GTR
30 HGMD
31 HMDB
32 HPO
33 ICD10
34 ICD10 via Orphanet
35 ICD9CM
36 IUPHAR
37 KEGG
38 LifeMap
40 LOVD
42 MedGen
44 MeSH
45 MESH via Orphanet
46 MGI
49 NCI
50 NCIt
51 NDF-RT
54 NINDS
55 Novoseek
57 OMIM
58 OMIM via Orphanet
62 PubMed
64 QIAGEN
69 SNOMED-CT via HPO
70 SNOMED-CT via Orphanet
71 TGDB
72 Tocris
73 UMLS
74 UMLS via Orphanet
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