MCID: D2H001
MIFTS: 46

D-2-Hydroxyglutaric Aciduria

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

Aliases & Classifications for D-2-Hydroxyglutaric Aciduria

MalaCards integrated aliases for D-2-Hydroxyglutaric Aciduria:

Name: D-2-Hydroxyglutaric Aciduria 54 12 50 56 29 13 14 69
D-2-Hydroxyglutaric Aciduria 1 24 71 29 69
D-2-Hydroxyglutaric Acidemia 50 56
D-2-Hga 50 56
D2hga1 24 71
D2ha 50 71
Combined D-2- and L-2-Hydroxyglutaric Aciduria 69

Characteristics:

Orphanet epidemiological data:

56
d-2-hydroxyglutaric aciduria
Inheritance: Autosomal dominant,Autosomal recessive; Prevalence: <1/1000000 (Worldwide); Age of onset: Childhood,Infancy,Neonatal;

OMIM:

54
Inheritance:
autosomal recessive

Miscellaneous:
two different phenotypes exist - severe phenotype (early infantile onset, epileptic encephalopathy and often cardiomyopathy) and mild phenotype (more variable clinical presentation)
severe phenotype onset - neonate
mild phenotype onset - 11-18 months


HPO:

32
d-2-hydroxyglutaric aciduria:
Inheritance autosomal recessive inheritance


Classifications:



Summaries for D-2-Hydroxyglutaric Aciduria

NIH Rare Diseases : 50 d-2-alpha hydroxyglutaric aciduria is an inheritedmetabolic condition that is associated with progressive brain damage. signs and symptoms of this condition include developmental delay, seizures, 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. d-2-alpha hydroxyglutaric aciduria is caused by changes (mutations) in the d2hgdh gene and is inherited in an autosomal recessive manner. treatment is focused on alleviating the signs and symptoms of the condition, such as medications to control seizures. last updated: 10/28/2015

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 seizures, micrognathia and prominent forehead. An important gene associated with D-2-Hydroxyglutaric Aciduria is D2HGDH (D-2-Hydroxyglutarate Dehydrogenase), and among its related pathways/superpathways are Metabolism and Pyruvate metabolism and Citric Acid (TCA) cycle. Affiliated tissues include brain and skeletal muscle.

UniProtKB/Swiss-Prot : 71 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.

OMIM : 54
D-2-hydroxyglutaric aciduria is a neurometabolic disorder first described by Chalmers et al. (1980). Clinical symptoms include developmental delay, epilepsy, hypotonia, and dysmorphic features. Mild and severe phenotypes were characterized (van der Knaap et al., 1999). The severe phenotype is homogeneous and is characterized by early infantile-onset epileptic encephalopathy and, often, cardiomyopathy. The mild phenotype has a more variable clinical presentation. (600721)

Disease Ontology : 12 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.

Related Diseases for D-2-Hydroxyglutaric Aciduria

Diseases in the D-2-Hydroxyglutaric Aciduria family:

D-2-Hydroxyglutaric Aciduria 2

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

(show all 36)
id Related Disease Score Top Affiliating Genes
1 d-2-hydroxyglutaric aciduria 2 12.4
2 metaphyseal enchondromatosis with d-2-hydroxyglutaric aciduria 12.0
3 combined d-2- and l-2-hydroxyglutaric aciduria 11.6
4 2-hydroxyglutaric aciduria 11.2
5 optic disk drusen 10.7 IDH1 IDH2
6 nemaline myopathy 10.7 IDH1 IDH2
7 endolymphatic sac tumor 10.7 IDH1 IDH2
8 mixed oligodendroglioma-astrocytoma 10.7 IDH1 IDH2
9 congenital disorder of glycosylation, type if 10.7 IDH1 IDH2
10 anca-associated vasculitis 10.7 IDH1 IDH2
11 essential pentosuria 10.7 IDH1 IDH2
12 bone osteosarcoma 10.7 IDH1 IDH2
13 breast papillomatosis 10.7 IDH1 IDH2
14 acute pre-b-cell lymphoblastic leukemia 10.6 IDH1 IDH2
15 early myoclonic encephalopathy 10.6 IDH1 IDH2
16 neurotic disorder 10.6 IDH1 IDH2
17 juxtacortical chondrosarcoma 10.6 IDH1 IDH2
18 schwannoma of jugular foramen 10.6 IDH1 IDH2
19 seckel syndrome 7 10.4 GLS2 L2HGDH
20 allergic hypersensitivity disease 10.4 IDH1 IDH2
21 fallopian tube papillary adenocarcinoma 10.4 IDH1 IDH2
22 vascular cancer 10.3 IDH1 IDH2
23 corneal staphyloma 10.2 ACP5 PTH1R
24 bronchus cancer 10.1 ACP5 PTH1R
25 achard syndrome 10.1 IDH1 IDH2
26 funisitis 10.1 GRIN2A GRIN2B
27 cardiomyopathy 10.1
28 brachydactyly 10.0 D2HGDH GCDH IDH1 IDH2 L2HGDH
29 l-2-hydroxyglutaric aciduria 9.9
30 cortical blindness 9.9
31 cerebritis 9.9
32 neuropathy 9.9
33 hypotonia 9.9
34 fryns macrocephaly 9.8 ACP5 IDH1 IDH2 PTH1R
35 cri-du-chat syndrome 9.8 ACP5 IDH1 IDH2 PTH1R
36 systemic lupus erythematosus 2 5.0 ACP5 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 & Phenotypes for D-2-Hydroxyglutaric Aciduria

Symptoms via clinical synopsis from OMIM:

54

Neurologic- Central Nervous System:
hypotonia
mental retardation
seizures
delayed myelination
subependymal cysts
more
Muscle Soft Tissue:
muscle weakness

Cardiovascular- Heart:
cardiomyopathy (severe form)
aortic insufficiency

Abdomen- Gastroin testinal:
episodic vomiting (severe form)

Head And Neck- Face:
micrognathia
prominent forehead

Head And Neck- Head:
macrocephaly

Respiratory:
inspiratory stridor (severe form)
apnea (severe form)

Laboratory- Abnormalities:
d-2-hydroxyglutaric aciduria
elevated d-2-hydroxyglutaric acid (urine, plasma, csf)
elevated l-2-hydroxyglutaric acid (urine)
elevated 2-ketoglutarate (urine)


Clinical features from OMIM:

600721

Human phenotypes related to D-2-Hydroxyglutaric Aciduria:

32 (show all 21)
id Description HPO Frequency HPO Source Accession
1 seizures 32 HP:0001250
2 micrognathia 32 HP:0000347
3 prominent forehead 32 HP:0011220
4 frontal bossing 32 HP:0002007
5 global developmental delay 32 HP:0001263
6 muscle weakness 32 HP:0001324
7 apnea 32 HP:0002104
8 macrocephaly 32 HP:0000256
9 intellectual disability 32 HP:0001249
10 cardiomyopathy 32 HP:0001638
11 subependymal cysts 32 HP:0002416
12 muscular hypotonia 32 HP:0001252
13 multifocal cerebral white matter abnormalities 32 HP:0007052
14 d-2-hydroxyglutaric aciduria 32 HP:0012321
15 aortic regurgitation 32 HP:0001659
16 glutaric aciduria 32 HP:0003150
17 inspiratory stridor 32 HP:0005348
18 episodic vomiting 32 HP:0002572
19 infantile encephalopathy 32 HP:0007105
20 dilation of lateral ventricles 32 HP:0006956
21 delayed cns myelination 32 HP:0002188

UMLS symptoms related to D-2-Hydroxyglutaric Aciduria:


dyspnea, seizures, stridor, muscle weakness

Drugs & Therapeutics for D-2-Hydroxyglutaric Aciduria

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

Genetic Tests for D-2-Hydroxyglutaric Aciduria

Genetic tests related to D-2-Hydroxyglutaric Aciduria:

id Genetic test Affiliating Genes
1 D-2-Hydroxyglutaric Aciduria 1 29 24 D2HGDH
2 D-2-Hydroxyglutaric Aciduria 29

Anatomical Context for D-2-Hydroxyglutaric Aciduria

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

39
Brain, Skeletal Muscle

Publications for D-2-Hydroxyglutaric Aciduria

Articles related to D-2-Hydroxyglutaric Aciduria:

(show all 34)
id Title Authors Year
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
Co-morbidity of Sanfilippo syndrome type C and D-2-hydroxyglutaric aciduria. ( 21384162 )
2011
5
Whole-exome sequencing detects somatic mutations of IDH1 in metaphyseal chondromatosis with D-2-hydroxyglutaric aciduria (MC-HGA). ( 22025298 )
2011
6
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
7
IDH2 mutations in patients with D-2-hydroxyglutaric aciduria. ( 20847235 )
2010
8
Evidence for genetic heterogeneity in D-2-hydroxyglutaric aciduria. ( 20020533 )
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
Mutations in phenotypically mild D-2-hydroxyglutaric aciduria. ( 16037974 )
2005
13
Phenotypic heterogeneity in the presentation of D-2-hydroxyglutaric aciduria in monozygotic twins. ( 16081310 )
2005
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 and glutaric aciduria type 1 in siblings: coincidence, or linked disorders? ( 15248096 )
2004
16
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
17
Spondyloenchondromatosis with D-2-hydroxyglutaric aciduria: a report of a second patient with this unusual combination. ( 12868470 )
2003
18
D-2-hydroxyglutaric aciduria: a case with an intermediate phenotype and prenatal diagnosis of two affected fetuses. ( 12884432 )
2003
19
D-2-Hydroxyglutaric aciduria with absence of corpus callosum and neonatal intracranial haemorrhage. ( 12872850 )
2003
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 in a patient with a severe clinical phenotype and unusual MRI findings. ( 11999977 )
2002
22
D-2-Hydroxyglutaric aciduria and subdural haemorrhage. ( 12162609 )
2002
23
D-2-hydroxyglutaric aciduria in association with spondyloenchondromatosis. ( 10883451 )
2000
24
D-2-hydroxyglutaric aciduria with cerebral, vascular, and muscular abnormalities in a 14-year-old boy. ( 10921524 )
2000
25
D-2-hydroxyglutaric aciduria: further clinical delineation. ( 10407777 )
1999
26
D-2-Hydroxyglutaric aciduria: biochemical marker or clinical disease entity? ( 9894884 )
1999
27
Facial anomalies in D-2-hydroxyglutaric aciduria. ( 10449646 )
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

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

71
id Symbol AA change Variation ID SNP ID
1 D2HGDH p.Ile147Ser VAR_025890 rs121434361
2 D2HGDH p.Asp375Tyr VAR_025891 rs267606759
3 D2HGDH p.Asn439Asp VAR_025893 rs121434362
4 D2HGDH p.Val444Ala VAR_025894 rs121434360

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

6
id Gene Variation Type Significance SNP ID Assembly Location
1 D2HGDH NM_152783.4(D2HGDH): c.1331T> C (p.Val444Ala) single nucleotide variant Pathogenic rs121434360 GRCh37 Chromosome 2, 242707149: 242707149
2 D2HGDH NM_152783.4(D2HGDH): c.440T> G (p.Ile147Ser) single nucleotide variant Pathogenic rs121434361 GRCh37 Chromosome 2, 242681939: 242681939
3 D2HGDH D2HGDH, IVS1AS, A-G, -23 single nucleotide variant Pathogenic
4 D2HGDH D2HGDH, IVS4AS, A-G, -2 single nucleotide variant Pathogenic
5 D2HGDH NM_152783.4(D2HGDH): c.1315A> G (p.Asn439Asp) single nucleotide variant Pathogenic rs121434362 GRCh37 Chromosome 2, 242707133: 242707133
6 D2HGDH D2HGDH, 2-BP DUP, 326TC duplication Pathogenic
7 D2HGDH NM_152783.4(D2HGDH): c.1123G> T (p.Asp375Tyr) single nucleotide variant Pathogenic rs267606759 GRCh37 Chromosome 2, 242690786: 242690786
8 D2HGDH NM_152783.4(D2HGDH): c.566C> T (p.Pro189Leu) single nucleotide variant Pathogenic rs587783517 GRCh38 Chromosome 2, 241743697: 241743697
9 D2HGDH NM_152783.4(D2HGDH): c.1027delT (p.Ser343Glnfs) deletion Pathogenic rs797045506 GRCh38 Chromosome 2, 241751275: 241751275

Expression for D-2-Hydroxyglutaric Aciduria

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

Pathways for D-2-Hydroxyglutaric Aciduria

GO Terms for D-2-Hydroxyglutaric Aciduria

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

id Name GO ID Score Top Affiliating Genes
1 mitochondrion GO:0005739 9.61 ADHFE1 ALDH5A1 D2HGDH DECR1 GCDH GLS2
2 mitochondrial matrix GO:0005759 9.17 ADHFE1 ALDH5A1 D2HGDH DECR1 GCDH GLS2
3 NMDA selective glutamate receptor complex GO:0017146 9.16 GRIN2A GRIN2B

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

id Name GO ID Score Top Affiliating Genes
1 oxidation-reduction process GO:0055114 9.56 ADHFE1 ALDH5A1 D2HGDH DECR1 GCDH IDH1
2 tricarboxylic acid cycle GO:0006099 9.48 IDH1 IDH2
3 ionotropic glutamate receptor signaling pathway GO:0035235 9.46 GRIN2A GRIN2B
4 bone resorption GO:0045453 9.43 ACP5 PTH1R
5 respiratory electron transport chain GO:0022904 9.4 ALDH5A1 D2HGDH
6 glutamine metabolic process GO:0006541 9.37 ALDH5A1 GLS2
7 glutamate receptor signaling pathway GO:0007215 9.32 GRIN2A GRIN2B
8 isocitrate metabolic process GO:0006102 9.26 IDH1 IDH2
9 glyoxylate cycle GO:0006097 9.16 IDH1 IDH2
10 2-oxoglutarate metabolic process GO:0006103 9.02 ADHFE1 D2HGDH IDH1 IDH2 L2HGDH

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

id Name GO ID Score Top Affiliating Genes
1 oxidoreductase activity, acting on the CH-OH group of donors, NAD or NADP as acceptor GO:0016616 9.48 IDH1 IDH2
2 extracellular-glutamate-gated ion channel activity GO:0005234 9.46 GRIN2A GRIN2B
3 ionotropic glutamate receptor activity GO:0004970 9.43 GRIN2A GRIN2B
4 glycine binding GO:0016594 9.4 GRIN2B GSS
5 NMDA glutamate receptor activity GO:0004972 9.37 GRIN2A GRIN2B
6 NAD binding GO:0051287 9.32 IDH1 IDH2
7 isocitrate dehydrogenase (NADP+) activity GO:0004450 9.26 IDH1 IDH2
8 oxidoreductase activity GO:0016491 9.23 ADHFE1 ALDH5A1 D2HGDH DECR1 GCDH IDH1
9 isocitrate dehydrogenase activity GO:0004448 9.16 IDH1 IDH2
10 (R)-2-hydroxyglutarate dehydrogenase activity GO:0051990 8.96 D2HGDH IDH1

Sources for D-2-Hydroxyglutaric Aciduria

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
16 ExPASy
18 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 MedGen
42 MeSH
43 MESH via Orphanet
44 MGI
46 NCI
47 NCIt
48 NDF-RT
51 NINDS
52 Novoseek
54 OMIM
55 OMIM via Orphanet
59 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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