MCID: D2H001
MIFTS: 45

D-2-Hydroxyglutaric Aciduria malady

Categories: Genetic diseases, Neuronal diseases, Metabolic diseases, Rare diseases

Aliases & Classifications for D-2-Hydroxyglutaric Aciduria

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Aliases & Descriptions for D-2-Hydroxyglutaric Aciduria:

Name: D-2-Hydroxyglutaric Aciduria 50 11 13 52 12 66
D-2-Hydroxyglutaric Aciduria 1 23 68 25 66
D2hga1 23 68
Combined D-2- and L-2-Hydroxyglutaric Aciduria 66
 
D-2-Hydroxyglutaric Acidemia 52
D-2-Hga 52
D2ha 68

Characteristics:

Orphanet epidemiological data:

52
d-2-hydroxyglutaric aciduria:
Inheritance: Autosomal dominant,Autosomal recessive; Prevalence: <1/1000000 (Worldwide); Age of onset: Childhood,Infancy,Neonatal

HPO:

62
d-2-hydroxyglutaric aciduria:
Inheritance: autosomal recessive inheritance


Classifications:



External Ids:

OMIM50 600721
Disease Ontology11 DOID:0050575
Orphanet52 ORPHA79315
ICD10 via Orphanet29 E72.8
MeSH37 D020739

Summaries for D-2-Hydroxyglutaric Aciduria

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OMIM:50 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 enchondromatosis with d-2-hydroxyglutaric aciduria, and has symptoms including dyspnea, seizures and stridor. An important gene associated with D-2-Hydroxyglutaric Aciduria is D2HGDH (D-2-Hydroxyglutarate Dehydrogenase), and among its related pathways are Reelin signaling pathway and Hypothetical Network for Drug Addiction. Affiliated tissues include brain and skeletal muscle.

Disease Ontology:11 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:68 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

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

(show all 38)
idRelated DiseaseScoreTop Affiliating Genes
1d-2-hydroxyglutaric aciduria 212.4
2metaphyseal enchondromatosis with d-2-hydroxyglutaric aciduria12.2
3combined d-2- and l-2-hydroxyglutaric aciduria11.5
4d-2-alpha hydroxyglutaric aciduria11.0
5subserous uterine fibroid10.7IDH1, IDH2
6spinal cord disease10.7IDH1, IDH2
7endomyocardial fibroelastosis10.7IDH1, IDH2
8cystinosis, nephropathic10.7IDH1, IDH2
9maxillary sinus squamous cell carcinoma10.7IDH1, IDH2
10anaplastic small cell lymphoma10.7IDH1, IDH2
11dyserythropoietic anemia and thrombocytopenia10.6IDH1, IDH2
12gliofibroma10.6IDH1, IDH2
13benign breast phyllodes tumor10.6IDH1, IDH2
14juvenile astrocytoma10.6IDH1, IDH2
15pericardial tuberculosis10.6IDH1, IDH2
16intrahepatic bile duct cystadenoma10.6IDH1, IDH2
17capgras syndrome10.5IDH1, IDH2
18seckel syndrome 710.5GLS2, L2HGDH
19early myoclonic encephalopathy10.5IDH1, IDH2
20kernicterus due to isoimmunization10.4IDH1, IDH2
21vascular cancer10.4IDH1, IDH2
222-hydroxyglutaric aciduria10.3
23impotence10.3ACP5, PTH1R
24papillary thymic adenocarcinoma10.3IDH1, IDH2
25cyclosporiasis10.2ACP5, PTH1R
26cardiomyopathy10.2
27funisitis10.1GRIN2A, GRIN2B
28l-2-hydroxyglutaric aciduria10.0
29cortical blindness10.0
30cerebritis10.0
31neuropathy10.0
32hypotonia10.0
33brachydactyly10.0D2HGDH, GCDH, IDH1, IDH2, L2HGDH
34limb defects, distal transverse, with mental retardation and spasticity10.0GRIN2A, GRIN2B
35fryns macrocephaly9.8ACP5, IDH1, IDH2, PTH1R
36neuropathy, ataxia, and retinitis pigmentosa9.8ACP5, IDH1, IDH2, PTH1R
37alcohol-related neurodevelopmental disorder9.7GRIN2A, GRIN2B
38d-2-hydroxyglutaric aciduria5.2ACP5, 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 21)
id Description Frequency HPO Source Accession
1 macrocephaly HP:0000256
2 micrognathia HP:0000347
3 intellectual disability HP:0001249
4 seizures HP:0001250
5 muscular hypotonia HP:0001252
6 global developmental delay HP:0001263
7 muscle weakness HP:0001324
8 cardiomyopathy HP:0001638
9 aortic regurgitation HP:0001659
10 frontal bossing HP:0002007
11 apnea HP:0002104
12 delayed cns myelination HP:0002188
13 subependymal cysts HP:0002416
14 episodic vomiting HP:0002572
15 glutaric aciduria HP:0003150
16 inspiratory stridor HP:0005348
17 dilation of lateral ventricles HP:0006956
18 multifocal cerebral white matter abnormalities HP:0007052
19 infantile encephalopathy HP:0007105
20 prominent forehead HP:0011220
21 d-2-hydroxyglutaric aciduria HP:0012321

UMLS symptoms related to D-2-Hydroxyglutaric Aciduria:


dyspnea, seizures, stridor, muscle weakness

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 125 23 D2HGDH

Anatomical Context for D-2-Hydroxyglutaric Aciduria

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

34
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 34)
idTitleAuthorsYear
1
A small molecule inhibitor of mutant IDH2 rescues cardiomyopathy in a D-2-hydroxyglutaric aciduria type II mouse model. (27469509)
2016
2
Novel cases of D-2-hydroxyglutaric aciduria with IDH1 or IDH2 mosaic mutations identified by amplicon deep sequencing. (24049096)
2013
3
Metaphyseal chondromatosis combined with D-2-hydroxyglutaric aciduria in four patients. (22639207)
2012
4
Whole-exome sequencing detects somatic mutations of IDH1 in metaphyseal chondromatosis with D-2-hydroxyglutaric aciduria (MC-HGA). (22025298)
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
Co-morbidity of Sanfilippo syndrome type C and D-2-hydroxyglutaric aciduria. (21384162)
2011
7
Evidence for genetic heterogeneity in D-2-hydroxyglutaric aciduria. (20020533)
2010
8
IDH2 mutations in patients with D-2-hydroxyglutaric aciduria. (20847235)
2010
9
Peripheral neuropathy in a patient with D-2-hydroxyglutaric aciduria. (19169842)
2009
10
D-2-Hydroxyglutaric aciduria in three patients with proven SSADH deficiency: genetic coincidence or a related biochemical epiphenomenon? (16442322)
2006
11
D-2-Hydroxyglutaric aciduria: unravelling the biochemical pathway and the genetic defect. (16601864)
2006
12
Phenotypic heterogeneity in the presentation of D-2-hydroxyglutaric aciduria in monozygotic twins. (16081310)
2005
13
Mutations in phenotypically mild D-2-hydroxyglutaric aciduria. (16037974)
2005
14
D-2-hydroxyglutaric aciduria and glutaric aciduria type 1 in siblings: coincidence, or linked disorders? (15248096)
2004
15
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
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: a case with an intermediate phenotype and prenatal diagnosis of two affected fetuses. (12884432)
2003
20
D-2-Hydroxyglutaric aciduria in a patient with a severe clinical phenotype and unusual MRI findings. (11999977)
2002
21
NMDA receptor activation and respiratory chain complex V inhibition contribute to neurodegeneration in d-2-hydroxyglutaric aciduria. (12153528)
2002
22
D-2-Hydroxyglutaric aciduria and subdural haemorrhage. (12162609)
2002
23
D-2-hydroxyglutaric aciduria with cerebral, vascular, and muscular abnormalities in a 14-year-old boy. (10921524)
2000
24
D-2-hydroxyglutaric aciduria in association with spondyloenchondromatosis. (10883451)
2000
25
Facial anomalies in D-2-hydroxyglutaric aciduria. (10449646)
1999
26
D-2-hydroxyglutaric aciduria: further clinical delineation. (10407777)
1999
27
D-2-Hydroxyglutaric aciduria: biochemical marker or clinical disease entity? (9894884)
1999
28
D-2-hydroxyglutaric aciduria: evidence of clinical and biochemical heterogeneity. (9686368)
1998
29
D-2-hydroxyglutaric aciduria: hypotonia, cortical blindness, seizures, cardiomyopathy, and cylindrical spirals in skeletal muscle. (9010793)
1997
30
Clinical and MRI findings in a case of D-2-hydroxyglutaric aciduria. (7625550)
1995
31
D-2-hydroxyglutaric aciduria. (7782605)
1995
32
D-2-hydroxyglutaric aciduria in neonate with seizures and CNS dysfunction. (7515241)
1994
33
D-2-hydroxyglutaric aciduria in a newborn with neurological abnormalities: a new neurometabolic disorder? (7609436)
1993
34
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:

68
id Symbol AA change Variation ID SNP ID
1D2HGDHp.Ile147SerVAR_025890rs121434361
2D2HGDHp.Asp375TyrVAR_025891rs267606759
3D2HGDHp.Asn439AspVAR_025893rs121434362
4D2HGDHp.Val444AlaVAR_025894rs121434360

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

5
id Gene Variation Type Significance SNP ID Assembly Location
1D2HGDHNM_152783.4(D2HGDH): c.566C> T (p.Pro189Leu)single nucleotide variantPathogenicrs587783517GRCh37Chr 2, 242683112: 242683112
2D2HGDHNM_152783.4(D2HGDH): c.1331T> C (p.Val444Ala)single nucleotide variantPathogenicrs121434360GRCh37Chr 2, 242707149: 242707149
3D2HGDHNM_152783.4(D2HGDH): c.440T> G (p.Ile147Ser)single nucleotide variantPathogenicrs121434361GRCh37Chr 2, 242681939: 242681939
4D2HGDHD2HGDH, IVS1AS, A-G, -23single nucleotide variantPathogenic
5D2HGDHD2HGDH, IVS4AS, A-G, -2single nucleotide variantPathogenic
6D2HGDHNM_152783.4(D2HGDH): c.1315A> G (p.Asn439Asp)single nucleotide variantPathogenicrs121434362GRCh37Chr 2, 242707133: 242707133
7D2HGDHD2HGDH, 2-BP DUP, 326TCduplicationPathogenic
8D2HGDHNM_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:001714610.3GRIN2A, GRIN2B
2mitochondrial matrixGO:00057597.9ADHFE1, ALDH5A1, D2HGDH, DECR1, GCDH, GLS2
3mitochondrionGO:00057397.2ADHFE1, ALDH5A1, D2HGDH, DECR1, GCDH, GLS2

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

(show all 7)
idNameGO IDScoreTop Affiliating Genes
1glyoxylate cycleGO:000609710.5IDH1, IDH2
2isocitrate metabolic processGO:000610210.5IDH1, IDH2
3glutamate receptor signaling pathwayGO:000721510.0GRIN2A, GRIN2B
4ionotropic glutamate receptor signaling pathwayGO:00352359.9GRIN2A, GRIN2B
5bone resorptionGO:00454539.7ACP5, PTH1R
6tricarboxylic acid cycleGO:00060999.7IDH1, IDH2
72-oxoglutarate metabolic processGO:00061038.9ADHFE1, D2HGDH, IDH1, IDH2, L2HGDH

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

(show all 7)
idNameGO IDScoreTop Affiliating Genes
1isocitrate dehydrogenase activityGO:000444810.4IDH1, IDH2
2isocitrate dehydrogenase (NADP+) activityGO:000445010.4IDH1, IDH2
3extracellular-glutamate-gated ion channel activityGO:000523410.1GRIN2A, GRIN2B
4NMDA glutamate receptor activityGO:00049729.9GRIN2A, GRIN2B
5(R)-2-hydroxyglutarate dehydrogenase activityGO:00519909.9D2HGDH, IDH1
6glycine bindingGO:00165949.8GRIN2B, GSS
7NAD bindingGO:00512879.7ALDH5A1, IDH1, IDH2

Sources for D-2-Hydroxyglutaric Aciduria

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2CDC
6CNVD
10DGIdb
15ExPASy
16FDA
17FMA
25GTR
26HGMD
27HMDB
28ICD10
29ICD10 via Orphanet
30ICD9CM
31IUPHAR
32KEGG
35MedGen
37MeSH
38MESH via Orphanet
39MGI
42NCI
43NCIt
44NDF-RT
47NINDS
48Novoseek
50OMIM
51OMIM via Orphanet
55PubMed
56QIAGEN
61SNOMED-CT via Orphanet
65Tumor Gene Family of Databases
66UMLS
67UMLS via Orphanet