MCID: D2H001
MIFTS: 47

D-2-Hydroxyglutaric Aciduria malady

Genetic diseases, Neuronal diseases, Metabolic diseases, Rare diseases categories

Aliases & Classifications for D-2-Hydroxyglutaric Aciduria

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Sources:
49OMIM, 10Disease Ontology, 11diseasecard, 12DISEASES, 51Orphanet, 65UMLS, 67UniProtKB/Swiss-Prot, 22GeneTests, 24GTR, 28ICD10 via Orphanet, 34MedGen, 36MeSH
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Aliases & Descriptions for D-2-Hydroxyglutaric Aciduria:

Name: D-2-Hydroxyglutaric Aciduria 49 10 11 12 51 65
D-2-Hydroxyglutaric Aciduria 1 22 24 67
D2hga1 22 67
Combined D-2- and L-2-Hydroxyglutaric Aciduria 65
 
D-2-Hydroxyglutaric Acidemia 51
D-2-Hga 51
D2ha 67


Classifications:



Characteristics (Orphanet epidemiological data):

51
d-2-hydroxyglutaric aciduria:
Inheritance: Autosomal dominant,Autosomal recessive; Prevalence: <1/1000000 (Worldwide); Age of onset: All ages; Age of death: any age


External Ids:

OMIM49 600721
Disease Ontology10 DOID:0050575
Orphanet51 79315
ICD10 via Orphanet28 E72.8
MeSH36 D020739

Summaries for D-2-Hydroxyglutaric Aciduria

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OMIM:49 D-2-hydroxyglutaric aciduria is a neurometabolic disorder first described by Chalmers et al. (1980). Clinical symptoms... (600721) more...

MalaCards based summary: D-2-Hydroxyglutaric Aciduria, also known as d-2-hydroxyglutaric aciduria 1, is related to d-2-hydroxyglutaric aciduria 2 and metaphyseal chondromatosis with d-2-hydroxyglutaric aciduria, and has symptoms including autosomal recessive inheritance, macrocephaly and micrognathia. An important gene associated with D-2-Hydroxyglutaric Aciduria is D2HGDH (D-2-Hydroxyglutarate Dehydrogenase), and among its related pathways are nNOS Signaling at Neuronal Synapses and Reelin signaling pathway. Affiliated tissues include brain and skeletal muscle.

Disease Ontology:10 An 2-hydroxyglutaric aciduria that involves developmental delay, seizures, weak muscle tone (hypotonia), and abnormalities in the largest part of the brain (the cerebrum), which controls many important functions such as muscle movement, speech, vision, thinking, emotion, and memory.

UniProtKB/Swiss-Prot:67 D-2-hydroxyglutaric aciduria 1: A rare recessive neurometabolic disorder causing developmental delay, epilepsy, hypotonia, and dysmorphic features. Both a mild and a severe phenotype exist. The severe phenotype is homogeneous and is characterized by early infantile-onset epileptic encephalopathy and cardiomyopathy. The mild phenotype has a more variable clinical presentation. Diagnosis is based on the presence of an excess of D-2- hydroxyglutaric acid in the urine.

Related Diseases for D-2-Hydroxyglutaric Aciduria

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Diseases in the D-2-Hydroxyglutaric Aciduria family:

D-2-Hydroxyglutaric Aciduria 2 D-2-Alpha Hydroxyglutaric Aciduria
D,l-2-Hydroxyglutaric Aciduria

Diseases related to D-2-Hydroxyglutaric Aciduria via text searches within MalaCards or GeneCards Suite gene sharing:

(show all 37)
idRelated DiseaseScoreTop Affiliating Genes
1d-2-hydroxyglutaric aciduria 210.7
2metaphyseal chondromatosis with d-2-hydroxyglutaric aciduria10.6
32-hydroxyglutaric aciduria10.4
4d,l-2-hydroxyglutaric aciduria10.4
5alveolar periostitis10.3IDH1, IDH2
6malignant biphasic mesothelioma10.3IDH1, IDH2
7enchondromatosis dwarfism deafness10.3IDH1, IDH2
8congenital disorder of glycosylation, type if10.3IDH1, IDH2
9mixed astrocytoma-ependymoma10.3IDH1, IDH2
10small cell osteogenic sarcoma10.3IDH1, IDH2
11her2-receptor negative breast cancer10.3IDH1, IDH2
12breast leiomyoma10.3IDH1, IDH2
13l-2-hydroxyglutaric aciduria10.3
14combined d-2- and l-2-hydroxyglutaric aciduria10.3
15cortical blindness10.3
16cerebritis10.3
17neuropathy10.3
18peripheral neuropathy10.3
19cardiomyopathy10.3
20hypotonia10.3
21suppression amblyopia10.2IDH1, IDH2
22adult brain stem glioma10.2IDH1, IDH2
23choledochal cyst10.2IDH1, IDH2
24spindle cell carcinoma10.2IDH1, IDH2
25succinic semialdehyde dehydrogenase deficiency10.2ALDH5A1, D2HGDH
26benign peritoneal mesothelioma10.1IDH1, IDH2
27gastric papillary adenocarcinoma10.1IDH1, IDH2
28seckel syndrome 710.1GLS2, L2HGDH
29d-2-alpha hydroxyglutaric aciduria10.1
30dry eye syndrome10.1IDH1, IDH2
31hernia of ovary and fallopian tube10.1ACP5, PTH1R
32toxoplasmosis10.0ACP5, PTH1R
33adams-oliver syndrome9.9ACP5, IDH1, IDH2, PTH1R
34hydranencephaly9.9ACP5, IDH1, IDH2, PTH1R
35abdominal tuberculosis9.9ALDH5A1, D2HGDH, GCDH, IDH1, IDH2, L2HGDH
36fetishism9.9GRIN2A, GRIN2B
37d-2-hydroxyglutaric aciduria8.0ACP5, ADHFE1, ALDH5A1, D2HGDH, DECR1, GCDH

Graphical network of the top 20 diseases related to D-2-Hydroxyglutaric Aciduria:



Diseases related to d-2-hydroxyglutaric aciduria

Symptoms for D-2-Hydroxyglutaric Aciduria

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Symptoms by clinical synopsis from OMIM:

600721

Clinical features from OMIM:

600721

HPO human phenotypes related to D-2-Hydroxyglutaric Aciduria:

(show all 22)
id Description Frequency HPO Source Accession
1 autosomal recessive inheritance HP:0000007
2 macrocephaly HP:0000256
3 micrognathia HP:0000347
4 intellectual disability HP:0001249
5 seizures HP:0001250
6 muscular hypotonia HP:0001252
7 global developmental delay HP:0001263
8 muscle weakness HP:0001324
9 cardiomyopathy HP:0001638
10 aortic regurgitation HP:0001659
11 frontal bossing HP:0002007
12 apnea HP:0002104
13 delayed cns myelination HP:0002188
14 subependymal cysts HP:0002416
15 episodic vomiting HP:0002572
16 glutaric aciduria HP:0003150
17 inspiratory stridor HP:0005348
18 dilation of lateral ventricles HP:0006956
19 multifocal cerebral white matter abnormalities HP:0007052
20 infantile encephalopathy HP:0007105
21 prominent forehead HP:0011220
22 d-2-hydroxyglutaric aciduria HP:0012321

Drugs & Therapeutics for D-2-Hydroxyglutaric Aciduria

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Interventional clinical trials:

Search ClinicalTrials, NIH Clinical Center for D-2-Hydroxyglutaric Aciduria

Genetic Tests for D-2-Hydroxyglutaric Aciduria

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Genetic tests related to D-2-Hydroxyglutaric Aciduria:

id Genetic test Affiliating Genes
1 D-2-Hydroxyglutaric Aciduria 122 24 D2HGDH

Anatomical Context for D-2-Hydroxyglutaric Aciduria

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MalaCards organs/tissues related to D-2-Hydroxyglutaric Aciduria:

33
Brain, Skeletal muscle

Animal Models for D-2-Hydroxyglutaric Aciduria or affiliated genes

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Publications for D-2-Hydroxyglutaric Aciduria

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Articles related to D-2-Hydroxyglutaric Aciduria:

(show all 33)
idTitleAuthorsYear
1
Novel cases of D-2-hydroxyglutaric aciduria with IDH1 or IDH2 mosaic mutations identified by amplicon deep sequencing. (24049096)
2013
2
Metaphyseal chondromatosis combined with D-2-hydroxyglutaric aciduria in four patients. (22639207)
2012
3
Whole-exome sequencing detects somatic mutations of IDH1 in metaphyseal chondromatosis with D-2-hydroxyglutaric aciduria (MC-HGA). (22025298)
2011
4
Co-morbidity of Sanfilippo syndrome type C and D-2-hydroxyglutaric aciduria. (21384162)
2011
5
A lymphoblast model for IDH2 gain-of-function activity in d-2-hydroxyglutaric aciduria type II: novel avenues for biochemical and therapeutic studies. (21889589)
2011
6
Evidence for genetic heterogeneity in D-2-hydroxyglutaric aciduria. (20020533)
2010
7
IDH2 mutations in patients with D-2-hydroxyglutaric aciduria. (20847235)
2010
8
Peripheral neuropathy in a patient with D-2-hydroxyglutaric aciduria. (19169842)
2009
9
D-2-Hydroxyglutaric aciduria in three patients with proven SSADH deficiency: genetic coincidence or a related biochemical epiphenomenon? (16442322)
2006
10
D-2-Hydroxyglutaric aciduria: unravelling the biochemical pathway and the genetic defect. (16601864)
2006
11
Mutations in phenotypically mild D-2-hydroxyglutaric aciduria. (16037974)
2005
12
Phenotypic heterogeneity in the presentation of D-2-hydroxyglutaric aciduria in monozygotic twins. (16081310)
2005
13
D-2-hydroxyglutaric aciduria and glutaric aciduria type 1 in siblings: coincidence, or linked disorders? (15248096)
2004
14
Investigations by mass isotopomer analysis of the formation of D-2-hydroxyglutarate by cultured lymphoblasts from two patients with D-2-hydroxyglutaric aciduria. (14741351)
2004
15
D-2-hydroxyglutaric aciduria: a case with an intermediate phenotype and prenatal diagnosis of two affected fetuses. (12884432)
2003
16
Spondyloenchondromatosis with D-2-hydroxyglutaric aciduria: a report of a second patient with this unusual combination. (12868470)
2003
17
Disease-related metabolites in culture medium of fibroblasts from patients with D-2-hydroxyglutaric aciduria, L-2-hydroxyglutaric aciduria, and combined D/L-2-hydroxyglutaric aciduria. (12816910)
2003
18
D-2-Hydroxyglutaric aciduria with absence of corpus callosum and neonatal intracranial haemorrhage. (12872850)
2003
19
D-2-Hydroxyglutaric aciduria in a patient with a severe clinical phenotype and unusual MRI findings. (11999977)
2002
20
NMDA receptor activation and respiratory chain complex V inhibition contribute to neurodegeneration in d-2-hydroxyglutaric aciduria. (12153528)
2002
21
D-2-Hydroxyglutaric aciduria and subdural haemorrhage. (12162609)
2002
22
D-2-hydroxyglutaric aciduria with cerebral, vascular, and muscular abnormalities in a 14-year-old boy. (10921524)
2000
23
D-2-hydroxyglutaric aciduria in association with spondyloenchondromatosis. (10883451)
2000
24
Facial anomalies in D-2-hydroxyglutaric aciduria. (10449646)
1999
25
D-2-Hydroxyglutaric aciduria: biochemical marker or clinical disease entity? (9894884)
1999
26
D-2-hydroxyglutaric aciduria: further clinical delineation. (10407777)
1999
27
D-2-hydroxyglutaric aciduria: evidence of clinical and biochemical heterogeneity. (9686368)
1998
28
D-2-hydroxyglutaric aciduria: hypotonia, cortical blindness, seizures, cardiomyopathy, and cylindrical spirals in skeletal muscle. (9010793)
1997
29
D-2-hydroxyglutaric aciduria. (7782605)
1995
30
Clinical and MRI findings in a case of D-2-hydroxyglutaric aciduria. (7625550)
1995
31
D-2-hydroxyglutaric aciduria in neonate with seizures and CNS dysfunction. (7515241)
1994
32
D-2-hydroxyglutaric aciduria in a newborn with neurological abnormalities: a new neurometabolic disorder? (7609436)
1993
33
D-2-hydroxyglutaric aciduria: case report and biochemical studies. (6774165)
1980

Variations for D-2-Hydroxyglutaric Aciduria

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UniProtKB/Swiss-Prot genetic disease variations for D-2-Hydroxyglutaric Aciduria:

67
id Symbol AA change Variation ID SNP ID
1D2HGDHp.Ile147SerVAR_025890
2D2HGDHp.Asp375TyrVAR_025891
3D2HGDHp.Asn439AspVAR_025893
4D2HGDHp.Val444AlaVAR_025894

Clinvar genetic disease variations for D-2-Hydroxyglutaric Aciduria:

5
id Gene Variation Type Significance SNP ID Assembly Location
1IDH2NM_002168.3(IDH2): c.419G> A (p.Arg140Gln)single nucleotide variantPathogenicrs121913502GRCh37Chr 15, 90631934: 90631934
2IDH2NM_001289910.1(IDH2): c.262C> G (p.Arg88Gly)single nucleotide variantPathogenicrs267606870GRCh37Chr 15, 90631935: 90631935
3D2HGDHNM_152783.4(D2HGDH): c.566C> T (p.Pro189Leu)single nucleotide variantPathogenicrs587783517GRCh37Chr 2, 242683112: 242683112
4D2HGDHNM_152783.4(D2HGDH): c.1331T> C (p.Val444Ala)single nucleotide variantPathogenicrs121434360GRCh37Chr 2, 242707149: 242707149
5D2HGDHNM_152783.4(D2HGDH): c.440T> G (p.Ile147Ser)single nucleotide variantPathogenicrs121434361GRCh37Chr 2, 242681939: 242681939
6D2HGDHD2HGDH, IVS1AS, A-G, -23single nucleotide variantPathogenic
7D2HGDHD2HGDH, IVS4AS, A-G, -2single nucleotide variantPathogenic
8D2HGDHNM_152783.4(D2HGDH): c.1315A> G (p.Asn439Asp)single nucleotide variantPathogenicrs121434362GRCh37Chr 2, 242707133: 242707133
9D2HGDHD2HGDH, 2-BP DUP, 326TCduplicationPathogenic
10D2HGDHNM_152783.4(D2HGDH): c.1123G> T (p.Asp375Tyr)single nucleotide variantPathogenicrs267606759GRCh37Chr 2, 242690786: 242690786

Expression for genes affiliated with D-2-Hydroxyglutaric Aciduria

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Search GEO for disease gene expression data for D-2-Hydroxyglutaric Aciduria.

Pathways for genes affiliated with D-2-Hydroxyglutaric Aciduria

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GO Terms for genes affiliated with D-2-Hydroxyglutaric Aciduria

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Cellular components related to D-2-Hydroxyglutaric Aciduria according to GeneCards Suite gene sharing:

idNameGO IDScoreTop Affiliating Genes
1NMDA selective glutamate receptor complexGO:001714610.2GRIN2A, GRIN2B
2mitochondrial matrixGO:00057597.7ADHFE1, ALDH5A1, D2HGDH, DECR1, GCDH, GLS2
3mitochondrionGO:00057396.9ADHFE1, ALDH5A1, D2HGDH, DECR1, GCDH, GLS2

Biological processes related to D-2-Hydroxyglutaric Aciduria according to GeneCards Suite gene sharing:

(show all 16)
idNameGO IDScoreTop Affiliating Genes
1glyoxylate cycleGO:000609710.7IDH1, IDH2
2isocitrate metabolic processGO:000610210.7IDH1, IDH2
3tricarboxylic acid cycleGO:000609910.6IDH1, IDH2
4response to manganese ionGO:001004210.4D2HGDH, GRIN2A
5glutamine metabolic processGO:000654110.4ALDH5A1, GLS2
6glutamate receptor signaling pathwayGO:000721510.3GRIN2A, GRIN2B
7startle responseGO:000196410.2GRIN2A, GRIN2B
8regulation of postsynaptic membrane potentialGO:006007810.2GRIN2A, GRIN2B
9excitatory postsynaptic potentialGO:006007910.2GRIN2A, GRIN2B
10ionotropic glutamate receptor signaling pathwayGO:003523510.2GRIN2A, GRIN2B
11bone resorptionGO:004545310.1ACP5, PTH1R
12cellular metabolic processGO:00442379.5ADHFE1, D2HGDH, IDH2, L2HGDH
132-oxoglutarate metabolic processGO:00061039.4ADHFE1, D2HGDH, IDH1, IDH2, L2HGDH
14synaptic transmissionGO:00072688.7ALDH5A1, GLS2, GRIN2A, GRIN2B
15oxidation-reduction processGO:00551147.5ADHFE1, ALDH5A1, D2HGDH, DECR1, GCDH, IDH1
16small molecule metabolic processGO:00442816.4ACP5, ADHFE1, D2HGDH, DECR1, GCDH, GLS2

Molecular functions related to D-2-Hydroxyglutaric Aciduria according to GeneCards Suite gene sharing:

(show all 9)
idNameGO IDScoreTop Affiliating Genes
1isocitrate dehydrogenase (NADP+) activityGO:000445010.5IDH1, IDH2
2oxidoreductase activity, acting on the CH-OH group of donors, NAD or NADP as acceptorGO:001661610.3IDH1, IDH2
3glycine bindingGO:001659410.2GRIN2B, GSS
4ionotropic glutamate receptor activityGO:000497010.1GRIN2A, GRIN2B
5extracellular-glutamate-gated ion channel activityGO:000523410.1GRIN2A, GRIN2B
6NMDA glutamate receptor activityGO:000497210.1GRIN2A, GRIN2B
7NAD bindingGO:005128710.1ALDH5A1, IDH1, IDH2
8cation channel activityGO:000526110.0GRIN2A, GRIN2B
9oxidoreductase activityGO:00164918.3ADHFE1, ALDH5A1, D2HGDH, DECR1, L2HGDH

Sources for D-2-Hydroxyglutaric Aciduria

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2CDC
14ExPASy
15FDA
16FMA
24GTR
25HGMD
26HMDB
27ICD10
28ICD10 via Orphanet
29ICD9CM
30IUPHAR
31KEGG
34MedGen
36MeSH
37MESH via Orphanet
38MGI
41NCI
42NCIt
43NDF-RT
46NINDS
47Novoseek
49OMIM
50OMIM via Orphanet
54PubMed
55QIAGEN
60SNOMED-CT via Orphanet
64Tumor Gene Family of Databases
65UMLS
66UMLS via Orphanet