MCID: ALP011
MIFTS: 37

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 58 54 60 30 13 6 41 74
Oxoglutaric Aciduria 58 60
2 Alpha Ketoglutarate Dehydrogenase Deficiency 54
2-Ketoglutarate Dehydrogenase Deficiency 58
Alpha-Kgd Deficiency 58
Alpha Kgd Deficiency 54
Oxoglutaricaciduria 54

Characteristics:

Orphanet epidemiological data:

60
oxoglutaric aciduria
Inheritance: Autosomal recessive; Age of onset: Neonatal; Age of death: early childhood;

OMIM:

58
Inheritance:
autosomal recessive


HPO:

33
alpha-ketoglutarate dehydrogenase deficiency:
Clinical modifier death in childhood
Inheritance autosomal recessive inheritance


Classifications:



External Ids:

OMIM 58 203740
MESH via Orphanet 46 C536582
ICD10 via Orphanet 35 E88.8
UMLS via Orphanet 75 C2752074
Orphanet 60 ORPHA31
MedGen 43 C2752074
UMLS 74 C2752074

Summaries for Alpha-Ketoglutarate Dehydrogenase Deficiency

NIH Rare Diseases : 54 The following summary is from Orphanet, a European reference portal for information on rare diseases and orphan drugs.Orpha Number: 31Disease definitionA 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.Visit the Orphanet disease page for more resources.

MalaCards based summary : Alpha-Ketoglutarate Dehydrogenase Deficiency, also known as oxoglutaric aciduria, is related to lactic acidosis and dihydrolipoamide dehydrogenase deficiency. 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

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 29.4 DLD PDHA1
2 dihydrolipoamide dehydrogenase deficiency 10.3
3 wernicke-korsakoff syndrome 9.8 DLST OGDH
4 pyruvate dehydrogenase e3-binding protein deficiency 9.7 DLD PDHA1
5 maple syrup urine disease 9.6 DLD OGDH

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:

60 33 (show all 16)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 ataxia 60 33 hallmark (90%) Very frequent (99-80%) HP:0001251
2 global developmental delay 60 33 hallmark (90%) Very frequent (99-80%) HP:0001263
3 short stature 60 33 hallmark (90%) Very frequent (99-80%) HP:0004322
4 hypertonia 60 33 hallmark (90%) Very frequent (99-80%) HP:0001276
5 skeletal muscle atrophy 60 33 hallmark (90%) Very frequent (99-80%) HP:0003202
6 abnormality of krebs cycle metabolism 60 33 hallmark (90%) Very frequent (99-80%) HP:0000816
7 abnormal urine alpha-ketoglutarate concentration 60 33 hallmark (90%) Very frequent (99-80%) HP:0012401
8 hydrocephalus 60 33 frequent (33%) Frequent (79-30%) HP:0000238
9 abnormality of movement 60 33 frequent (33%) Frequent (79-30%) HP:0100022
10 abnormal salivary gland morphology 33 frequent (33%) HP:0010286
11 muscular hypotonia 33 HP:0001252
12 increased serum lactate 33 HP:0002151
13 metabolic acidosis 33 HP:0001942
14 generalized hypotonia 33 HP:0001290
15 abnormality of the salivary glands 60 Frequent (79-30%)
16 congenital lactic acidosis 33 HP:0004902

Symptoms via clinical synopsis from OMIM:

58
Metabolic:
metabolic acidosis
congenital lactic acidosis

Lab:
hyperlactatemia
alpha-ketoglutarate dehydrogenase deficiency

Neuro:
hypotonia

Misc:
early childhood death

Clinical features from OMIM:

203740

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

27 (show all 16)
# Description GenomeRNAi Source Accession Score Top Affiliating Genes
1 Decreased shRNA abundance (Z-score < -2) GR00366-A-160 9.5 OGDH
2 Decreased shRNA abundance (Z-score < -2) GR00366-A-18 9.5 PDHA1
3 Decreased shRNA abundance (Z-score < -2) GR00366-A-191 9.5 PDHA1
4 Decreased shRNA abundance (Z-score < -2) GR00366-A-48 9.5 OGDH
5 Decreased shRNA abundance (Z-score < -2) GR00366-A-60 9.5 PDHA1
6 Decreased shRNA abundance (Z-score < -2) GR00366-A-68 9.5 OGDH PDHA1
7 Increased shRNA abundance (Z-score > 2) GR00366-A-100 9.36 DLST
8 Increased shRNA abundance (Z-score > 2) GR00366-A-122 9.36 PDHA1
9 Increased shRNA abundance (Z-score > 2) GR00366-A-137 9.36 PDHA1
10 Increased shRNA abundance (Z-score > 2) GR00366-A-16 9.36 PDHA1
11 Increased shRNA abundance (Z-score > 2) GR00366-A-161 9.36 DLST
12 Increased shRNA abundance (Z-score > 2) GR00366-A-166 9.36 DLST PDHA1
13 Increased shRNA abundance (Z-score > 2) GR00366-A-42 9.36 PDHA1
14 Increased shRNA abundance (Z-score > 2) GR00366-A-47 9.36 DLST
15 Increased shRNA abundance (Z-score > 2) GR00366-A-82 9.36 DLST
16 Increased shRNA abundance (Z-score > 2) GR00366-A-83 9.36 DLST

MGI Mouse Phenotypes related to Alpha-Ketoglutarate Dehydrogenase Deficiency:

47
# 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 30 OGDH

Anatomical Context for Alpha-Ketoglutarate Dehydrogenase Deficiency

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

42
Skeletal Muscle, Salivary Gland

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
3
Hyper-2-oxoglutaric aciduria in long-term mental handicap. ( 3783660 )
1986
4
A familial progressive neurodegenerative disease with 2-oxoglutaric aciduria. ( 7075624 )
1982

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 13)
# Super pathways Score Top Affiliating Genes
1
Show member pathways
13.46 DLD DLST OGDH PDHA1
2
Show member pathways
13.2 DLD DLST OGDH PDHA1
3
Show member pathways
12.99 DLD DLST OGDH PDHA1
4 12.01 DLST PDHA1
5
Show member pathways
11.95 DLD DLST OGDH PDHA1
6
Show member pathways
11.68 DLD DLST OGDH PDHA1
7
Show member pathways
11.63 DLD DLST OGDH
8
Show member pathways
11.47 DLD DLST OGDH PDHA1
9
Show member pathways
11.3 DLD PDHA1
10 11.23 DLST OGDH
11 11.22 DLD DLST OGDH PDHA1
12
Show member pathways
11.03 DLD PDHA1
13
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 9.56 DLD DLST OGDH PDHA1
2 mitochondrial matrix GO:0005759 9.26 DLD DLST OGDH PDHA1
3 pyruvate dehydrogenase complex GO:0045254 9.16 DLD PDHA1
4 oxoglutarate dehydrogenase complex GO:0045252 8.8 DLD DLST OGDH

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 9.61 DLD OGDH PDHA1
2 generation of precursor metabolites and energy GO:0006091 9.4 DLST OGDH
3 mitochondrial acetyl-CoA biosynthetic process from pyruvate GO:0061732 9.37 DLD PDHA1
4 tricarboxylic acid cycle GO:0006099 9.33 DLST OGDH PDHA1
5 succinyl-CoA metabolic process GO:0006104 9.32 DLST OGDH
6 acetyl-CoA biosynthetic process from pyruvate GO:0006086 9.26 DLD PDHA1
7 2-oxoglutarate metabolic process GO:0006103 9.13 DLD DLST OGDH
8 histone succinylation GO:0106077 8.8 DLD DLST OGDH

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 EFO
18 ExPASy
20 FMA
29 GO
30 GTR
31 HGMD
32 HMDB
33 HPO
34 ICD10
35 ICD10 via Orphanet
36 ICD9CM
37 IUPHAR
38 KEGG
39 LifeMap
41 LOVD
43 MedGen
45 MeSH
46 MESH via Orphanet
47 MGI
50 NCI
51 NCIt
52 NDF-RT
55 NINDS
56 Novoseek
58 OMIM
59 OMIM via Orphanet
63 PubMed
65 QIAGEN
70 SNOMED-CT via HPO
71 SNOMED-CT via Orphanet
72 TGDB
73 Tocris
74 UMLS
75 UMLS via Orphanet
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