MCID: L2H001
MIFTS: 44

L-2-Hydroxyglutaric Aciduria

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

Aliases & Classifications for L-2-Hydroxyglutaric Aciduria

MalaCards integrated aliases for L-2-Hydroxyglutaric Aciduria:

Name: L-2-Hydroxyglutaric Aciduria 54 12 50 24 56 71 29 13 14 69
L-2-Hydroxyglutaric Acidemia 12 50 56 71 29 69
Combined D-2- and L-2-Hydroxyglutaric Aciduria 69
L-2-Hga 56
L2hga 71

Characteristics:

Orphanet epidemiological data:

56
l-2-hydroxyglutaric aciduria
Inheritance: Autosomal recessive; Prevalence: <1/1000000 (Worldwide); Age of onset: Childhood; Age of death: normal life expectancy;

OMIM:

54
Inheritance:
autosomal recessive

Miscellaneous:
onset in infancy or early childhood


HPO:

32
l-2-hydroxyglutaric aciduria:
Onset and clinical course infantile onset
Inheritance autosomal recessive inheritance


Classifications:



Summaries for L-2-Hydroxyglutaric Aciduria

NIH Rare Diseases : 50 l-2-hydroxyglutaric aciduria is an inheritedmetabolic condition that is associated with progressive brain damage. signs and symptoms of this condition typically begin during infancy or early childhood and may include developmental delay, seizures, speech difficulties, macrocephaly and abnormalities in a part of the brain called the cerebellum, which is involved in coordinating movement (i.e. balance and muscle coordination). l-2-hydroxyglutaric aciduria is caused by changes (mutations) in the l2hgdh 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 : L-2-Hydroxyglutaric Aciduria, also known as l-2-hydroxyglutaric acidemia, is related to combined d-2- and l-2-hydroxyglutaric aciduria and 2-hydroxyglutaric aciduria, and has symptoms including intellectual disability, severe, seizures and macrocephaly. An important gene associated with L-2-Hydroxyglutaric Aciduria is L2HGDH (L-2-Hydroxyglutarate Dehydrogenase), and among its related pathways/superpathways are Metabolism and Pyruvate metabolism and Citric Acid (TCA) cycle. Affiliated tissues include cerebellum, brain and liver.

Disease Ontology : 12 An 2-hydroxyglutaric aciduria that involves damage to cerebellum affecting movement coordination resulting in problems with balance and muscle coordination (ataxia).

UniProtKB/Swiss-Prot : 71 L-2-hydroxyglutaric aciduria: A rare autosomal recessive disorder clinically characterized by mild psychomotor delay in the first years of life, followed by progressive cerebellar ataxia, dysarthria and moderate to severe mental retardation. Diagnosis is based on the presence of an excess of L-2- hydroxyglutaric acid in urine, blood and cerebrospinal fluid.

Description from OMIM: 236792

Related Diseases for L-2-Hydroxyglutaric Aciduria

Diseases in the 2-Hydroxyglutaric Aciduria family:

L-2-Hydroxyglutaric Aciduria

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

(show all 20)
id Related Disease Score Top Affiliating Genes
1 combined d-2- and l-2-hydroxyglutaric aciduria 12.5
2 2-hydroxyglutaric aciduria 11.6
3 encephalopathy 10.1
4 d-2-hydroxyglutaric aciduria 10.0
5 epilepsy 10.0
6 meningitis 9.9
7 glioma 9.9
8 ataxia 9.9
9 tremor 9.9
10 cerebellar ataxia 9.9
11 medulloblastoma 9.9
12 hemiplegia 9.9
13 status epilepticus 9.9
14 lactic acidosis 9.9
15 gliomatosis cerebri 9.9
16 bacterial meningitis 9.9
17 systemic lupus erythematosus 2 9.5 GLS2 L2HGDH
18 adenylosuccinase lyase deficiency 9.4 GLS2 HMGCL
19 brachydactyly 9.4 L2HGDH MDH2 SLC25A1
20 seckel syndrome 7 7.5 GLS2 HMGCL L2HGDH MDH2 MLC1 SLC25A1

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



Diseases related to L-2-Hydroxyglutaric Aciduria

Symptoms & Phenotypes for L-2-Hydroxyglutaric Aciduria

Symptoms via clinical synopsis from OMIM:

54

Head And Neck- Eyes:
optic atrophy
nystagmus
strabismus

Head And Neck- Ears:
hearing loss

Neurologic- Central Nervous System:
pyramidal signs
seizures
mental retardation, severe
dysphasia
extrapyramidal signs
more
Laboratory- Abnormalities:
increased l-2-hydroxyglutaric acid in urine, serum, and csf
increased lysine in serum and csf


Clinical features from OMIM:

236792

Human phenotypes related to L-2-Hydroxyglutaric Aciduria:

56 32 (show all 27)
id Description HPO Frequency Orphanet Frequency HPO Source Accession
1 intellectual disability, severe 56 32 hallmark (90%) Very frequent (99-80%) HP:0010864
2 seizures 56 32 hallmark (90%) Very frequent (99-80%) HP:0001250
3 macrocephaly 56 32 frequent (33%) Frequent (79-30%) HP:0000256
4 encephalitis 56 32 hallmark (90%) Very frequent (99-80%) HP:0002383
5 dysphasia 56 32 occasional (7.5%) Occasional (29-5%) HP:0002357
6 muscular hypotonia 56 32 frequent (33%) Frequent (79-30%) HP:0001252
7 spastic tetraparesis 56 32 frequent (33%) Frequent (79-30%) HP:0001285
8 behavioral abnormality 56 32 frequent (33%) Frequent (79-30%) HP:0000708
9 aplasia/hypoplasia of the cerebellum 56 32 frequent (33%) Frequent (79-30%) HP:0007360
10 intellectual disability, progressive 56 32 hallmark (90%) Very frequent (99-80%) HP:0006887
11 abnormality of extrapyramidal motor function 56 32 frequent (33%) Frequent (79-30%) HP:0002071
12 neoplasm of the nervous system 56 32 frequent (33%) Frequent (79-30%) HP:0004375
13 optic atrophy 32 HP:0000648
14 nystagmus 32 HP:0000639
15 strabismus 32 HP:0000486
16 cerebellar atrophy 32 HP:0001272
17 leukoencephalopathy 32 HP:0002352
18 gliosis 32 HP:0002171
19 developmental regression 32 HP:0002376
20 hearing impairment 32 HP:0000365
21 corpus callosum atrophy 32 HP:0007371
22 severe demyelination of the white matter 32 HP:0007258
23 global brain atrophy 32 HP:0002283
24 abnormal pyramidal signs 32 HP:0007256
25 morphological abnormality of the pyramidal tract 32 HP:0002062
26 l-2-hydroxyglutaric aciduria 32 HP:0040144
27 l-2-hydroxyglutaric acidemia 32 HP:0040147

UMLS symptoms related to L-2-Hydroxyglutaric Aciduria:


seizures, abnormal pyramidal signs, abnormality of extrapyramidal motor function, dyspnea, stridor

Drugs & Therapeutics for L-2-Hydroxyglutaric Aciduria

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

Genetic Tests for L-2-Hydroxyglutaric Aciduria

Genetic tests related to L-2-Hydroxyglutaric Aciduria:

id Genetic test Affiliating Genes
1 L-2-Hydroxyglutaric Aciduria 29 24 L2HGDH
2 L-2-Hydroxyglutaric Acidemia 29

Anatomical Context for L-2-Hydroxyglutaric Aciduria

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

39
Cerebellum, Brain, Liver

Publications for L-2-Hydroxyglutaric Aciduria

Articles related to L-2-Hydroxyglutaric Aciduria:

(show top 50) (show all 82)
id Title Authors Year
1
Experimental evidence of oxidative stress in patients with l-2-hydroxyglutaric aciduria and that l-carnitine attenuates in vitro DNA damage caused by d-2-hydroxyglutaric and l-2-hydroxyglutaric acids. ( 28396261 )
2017
2
An L-2-Hydroxyglutaric Aciduria Case Presented With Acute Bacterial Meningitis. ( 28141777 )
2017
3
In-vivo brain H1-MR-Spectroscopy identification and quantification of 2-hydroxyglutarate in L-2-Hydroxyglutaric aciduria. ( 27543339 )
2016
4
Clinical features and disease progression of L-2-hydroxyglutaric aciduria in 27 Staffordshire bull terriers. ( 27729589 )
2016
5
Expanding the Clinical Spectrum of Mitochondrial Citrate Carrier (SLC25A1) Deficiency: Facial Dysmorphism in Siblings with Epileptic Encephalopathy and Combined D,L-2-Hydroxyglutaric Aciduria. ( 25614306 )
2015
6
Gliomatosis cerebri in L-2-hydroxyglutaric aciduria. ( 25997888 )
2015
7
A mouse model of L-2-hydroxyglutaric aciduria, a disorder of metabolite repair. ( 25763823 )
2015
8
A novel compound heterozygous mutation in a Chinese boy with L-2-hydroxyglutaric aciduria: a case study. ( 26208971 )
2015
9
White matter abnormalities in an adult patient with l-2-hydroxyglutaric aciduria. ( 25982940 )
2015
10
Founder effect confirmation of c.241A>G mutation in the L2HGDH gene and characterization of oxidative stress parameters in six Tunisian families with L-2-hydroxyglutaric aciduria. ( 24573090 )
2014
11
Clinical, neuroimaging, and genetic features of L-2-hydroxyglutaric aciduria in Arab kindreds. ( 24894778 )
2014
12
Successive distinct high-grade gliomas in L-2-hydroxyglutaric aciduria. ( 25338511 )
2014
13
Writer's cramp as a presentation of L-2-hydroxyglutaric aciduria. ( 26788335 )
2014
14
L-2-Hydroxyglutaric aciduria: a case report. ( 25033591 )
2014
15
L-2-Hydroxyglutaric Aciduria: Report of Two Indian Families. ( 24037495 )
2013
16
Deficiency in SLC25A1, encoding the mitochondrial citrate carrier, causes combined D-2- and L-2-hydroxyglutaric aciduria. ( 23561848 )
2013
17
A L2HGDH initiator methionine codon mutation in a Yorkshire terrier with L-2-hydroxyglutaric aciduria. ( 22834903 )
2012
18
L-2-hydroxyglutaric aciduria in two female Yorkshire terriers. ( 22843824 )
2012
19
L-2-hydroxyglutaric aciduria diagnosed in a young adult with progressive cerebellar ataxia and facial dyskinesia. ( 22030381 )
2012
20
Clinical, genetic and magnetic resonance findings in an Italian patient affected by L-2-hydroxyglutaric aciduria. ( 20859647 )
2011
21
L-2-hydroxyglutaric aciduria and multiple acyl-coenzyme A dehydrogenase deficiency are distinct metabolic disorders. ( 20168250 )
2010
22
L-2-hydroxyglutaric aciduria: report of four Turkish adult patients. ( 20065797 )
2010
23
Wilms tumor in a child with L-2-hydroxyglutaric aciduria. ( 20064066 )
2010
24
L-2-hydroxyglutaric aciduria diagnosed in an adult presenting with acute deterioration. ( 19760480 )
2010
25
L-2-hydroxyglutaric aciduria and brain tumors. ( 20421813 )
2010
26
A novel mutation as a cause of L-2-hydroxyglutaric aciduria. ( 19444541 )
2009
27
Sudden unexpected death in an infant with L-2-hydroxyglutaric aciduria. ( 19005678 )
2009
28
Development and implementation of a novel assay for L-2-hydroxyglutarate dehydrogenase (L-2-HGDH) in cell lysates: L-2-HGDH deficiency in 15 patients with L-2-hydroxyglutaric aciduria. ( 19821142 )
2009
29
Tracing the origin of L-2-hydroxyglutaric aciduria in a family. ( 19863265 )
2009
30
L-2-Hydroxyglutaric aciduria: pattern of MR imaging abnormalities in 56 patients. ( 19474378 )
2009
31
Riboflavin treatment in a case with l-2-hydroxyglutaric aciduria. ( 18343698 )
2009
32
L-2-hydroxyglutaric aciduria: clinical and molecular study in three Tunisian families. Identification of a new mutation and inter-familial phenotype variability. ( 18780161 )
2008
33
Epilepsy in a young adult caused by L-2-hydroxyglutaric aciduria: a case report. ( 18408399 )
2008
34
A successfully treated adult patient with L-2-hydroxyglutaric aciduria. ( 18362286 )
2008
35
L-2-hydroxyglutaric aciduria and brain tumors in children with mutations in the L2HGDH gene: neuroimaging findings. ( 18671189 )
2008
36
L-2-hydroxyglutaric aciduria: identification of ten novel mutations in the L2HGDH gene. ( 18415700 )
2008
37
Neuropathological findings in a Staffordshire bull terrier with l-2-hydroxyglutaric aciduria. ( 18295785 )
2008
38
L-2-Hydroxyglutaric aciduria presenting with severe autistic features. ( 17981416 )
2008
39
L-2-hydroxyglutaric aciduria: characterisation of the molecular defect in a spontaneous canine model. ( 17475916 )
2007
40
[L-2-hydroxyglutaric aciduria, an error of metabolism]. ( 18557388 )
2007
41
Mutation analysis a prerequisite for prenatal diagnosis of L-2-hydroxyglutaric aciduria? ( 17537659 )
2007
42
Osteoma of the calvaria in L-2-hydroxyglutaric aciduria. ( 17917788 )
2007
43
L-2-hydroxyglutaric aciduria, a defect of metabolite repair. ( 17603759 )
2007
44
Novel insights into L-2-hydroxyglutaric aciduria: mass isotopomer studies reveal 2-oxoglutaric acid as the metabolic precursor of L-2-hydroxyglutaric acid. ( 17876720 )
2007
45
Normal pregnancy outcome in L-2-hydroxyglutaric aciduria. ( 16802109 )
2006
46
L-2-hydroxyglutaric aciduria: a report of six cases and review of the literature. ( 16649364 )
2006
47
The gene mutated in L-2-hydroxyglutaric aciduria encodes L-2- hydroxyglutarate dehydrogenase. ( 16005139 )
2006
48
Hemiconvulsion-hemiplegia-epilepsy syndrome as a presenting feature of L-2-hydroxyglutaric aciduria. ( 16948946 )
2006
49
L-2-Hydroxyglutaric aciduria: clinical, genetic, and brain MRI characteristics in two adult sisters. ( 16722976 )
2006
50
Novel L2HGDH mutations in 21 patients with L-2-hydroxyglutaric aciduria of Portuguese origin. ( 16134148 )
2005

Variations for L-2-Hydroxyglutaric Aciduria

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

71
id Symbol AA change Variation ID SNP ID
1 L2HGDH p.Gly55Asp VAR_025682 rs118204021
2 L2HGDH p.Gly57Arg VAR_025683 rs199690954
3 L2HGDH p.Lys81Glu VAR_025684
4 L2HGDH p.His98Arg VAR_025685 rs267607206
5 L2HGDH p.His98Tyr VAR_025686
6 L2HGDH p.Glu176Asp VAR_025687
7 L2HGDH p.Pro302Leu VAR_025689 rs118204020
8 L2HGDH p.His434Pro VAR_025690 rs750044734

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

6
id Gene Variation Type Significance SNP ID Assembly Location
1 L2HGDH NM_024884.2(L2HGDH): c.905C> T (p.Pro302Leu) single nucleotide variant Pathogenic rs118204020 GRCh37 Chromosome 14, 50735882: 50735882
2 L2HGDH NM_024884.2(L2HGDH): c.1115delT (p.Met372Serfs) deletion Pathogenic rs786200869 GRCh37 Chromosome 14, 50732157: 50732157
3 L2HGDH NM_024884.2(L2HGDH): c.906+1G> T single nucleotide variant Pathogenic rs786200870 GRCh37 Chromosome 14, 50735880: 50735880
4 L2HGDH NM_024884.2(L2HGDH): c.164G> A (p.Gly55Asp) single nucleotide variant Pathogenic rs118204021 GRCh37 Chromosome 14, 50769712: 50769712
5 L2HGDH NC_000014.9: g.(50000000_?)_(?_50247254)del deletion Pathogenic GRCh38 Chromosome 14, 50000000: 50247254
6 L2HGDH NM_024884.2(L2HGDH): c.293A> G (p.His98Arg) single nucleotide variant Pathogenic rs267607206 GRCh37 Chromosome 14, 50768850: 50768850
7 L2HGDH NM_024884.2(L2HGDH): c.1003C> T (p.Arg335Ter) single nucleotide variant Pathogenic rs387907013 GRCh37 Chromosome 14, 50734532: 50734532
8 L2HGDH NM_024884.2(L2HGDH): c.465delA (p.Gly156Alafs) deletion Pathogenic rs797045678 GRCh38 Chromosome 14, 50294190: 50294190
9 L2HGDH NM_024884.2(L2HGDH): c.1015delA (p.Arg339Aspfs) deletion Pathogenic GRCh38 Chromosome 14, 50267802: 50267802
10 L2HGDH NM_024884.2(L2HGDH): c.584A> G (p.Tyr195Cys) single nucleotide variant Likely pathogenic rs887386390 GRCh37 Chromosome 14, 50750708: 50750708

Expression for L-2-Hydroxyglutaric Aciduria

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

Pathways for L-2-Hydroxyglutaric Aciduria

GO Terms for L-2-Hydroxyglutaric Aciduria

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

id Name GO ID Score Top Affiliating Genes
1 mitochondrion GO:0005739 9.35 GLS2 HMGCL L2HGDH MDH2 SLC25A1
2 mitochondrial matrix GO:0005759 9.33 GLS2 HMGCL MDH2
3 mitochondrial inner membrane GO:0005743 8.92 HMGCL L2HGDH MDH2 SLC25A1

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

id Name GO ID Score Top Affiliating Genes
1 gluconeogenesis GO:0006094 8.62 MDH2 SLC25A1

Sources for L-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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