MCID: L2H001
MIFTS: 42

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 57 12 53 59 75 37 29 13 6 15 73
L-2-Hydroxyglutaric Acidemia 57 12 53 59 75 29 73
L2hga 57 75
Combined D-2- and L-2-Hydroxyglutaric Aciduria 73
Aciduria, L-2-Hydroxyglutaric 40
L-2-Hga 59

Characteristics:

Orphanet epidemiological data:

59
l-2-hydroxyglutaric aciduria
Inheritance: Autosomal recessive; Prevalence: <1/1000000 (Worldwide); Age of onset: Childhood; Age of death: normal life expectancy;

OMIM:

57
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 : 53 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.

MalaCards based summary : L-2-Hydroxyglutaric Aciduria, also known as l-2-hydroxyglutaric acidemia, is related to 2-hydroxyglutaric aciduria and d-2-hydroxyglutaric aciduria 1, and has symptoms including seizures, abnormal pyramidal signs and abnormality of extrapyramidal motor function. An important gene associated with L-2-Hydroxyglutaric Aciduria is L2HGDH (L-2-Hydroxyglutarate Dehydrogenase), and among its related pathways/superpathways are Butanoate metabolism and Pyruvate metabolism and Citric Acid (TCA) cycle. Affiliated tissues include cerebellum, brain and liver, and related phenotypes are macrocephaly and behavioral abnormality

UniProtKB/Swiss-Prot : 75 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.

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

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 21)
# Related Disease Score Top Affiliating Genes
1 2-hydroxyglutaric aciduria 32.1 L2HGDH MDH2 SLC25A1
2 d-2-hydroxyglutaric aciduria 1 31.2 GLS2 L2HGDH
3 combined d-2- and l-2-hydroxyglutaric aciduria 12.7
4 encephalopathy 10.2
5 epilepsy 10.1
6 medulloblastoma 10.0
7 wilms tumor 5 10.0
8 aceruloplasminemia 10.0
9 ataxia-oculomotor apraxia 3 10.0
10 polyglucosan body myopathy 1 with or without immunodeficiency 10.0
11 wilms tumor 6 10.0
12 hemiplegia 10.0
13 status epilepticus 10.0
14 lactic acidosis 10.0
15 gliomatosis cerebri 10.0
16 bacterial meningitis 10.0
17 meningitis 10.0
18 glioma 10.0
19 tremor 10.0
20 idiopathic hemiconvulsion-hemiplegia syndrome 10.0
21 velocardiofacial syndrome 9.4 SLC25A1 SNAP29

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:

57
Head And Neck Eyes:
nystagmus
optic atrophy
strabismus

Head And Neck Ears:
hearing loss

Neurologic Central Nervous System:
seizures
dysphasia
spastic tetraparesis
extrapyramidal signs
pyramidal 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:

59 32 (show all 27)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 macrocephaly 59 32 frequent (33%) Frequent (79-30%) HP:0000256
2 behavioral abnormality 59 32 frequent (33%) Frequent (79-30%) HP:0000708
3 seizures 59 32 hallmark (90%) Very frequent (99-80%) HP:0001250
4 muscular hypotonia 59 32 frequent (33%) Frequent (79-30%) HP:0001252
5 spastic tetraparesis 59 32 frequent (33%) Frequent (79-30%) HP:0001285
6 abnormality of extrapyramidal motor function 59 32 frequent (33%) Frequent (79-30%) HP:0002071
7 dysphasia 59 32 occasional (7.5%) Occasional (29-5%) HP:0002357
8 encephalitis 59 32 hallmark (90%) Very frequent (99-80%) HP:0002383
9 neoplasm of the nervous system 59 32 frequent (33%) Frequent (79-30%) HP:0004375
10 intellectual disability, progressive 59 32 hallmark (90%) Very frequent (99-80%) HP:0006887
11 aplasia/hypoplasia of the cerebellum 59 32 frequent (33%) Frequent (79-30%) HP:0007360
12 intellectual disability, severe 59 32 hallmark (90%) Very frequent (99-80%) HP:0010864
13 hearing impairment 32 HP:0000365
14 strabismus 32 HP:0000486
15 nystagmus 32 HP:0000639
16 optic atrophy 32 HP:0000648
17 cerebellar atrophy 32 HP:0001272
18 morphological abnormality of the pyramidal tract 32 HP:0002062
19 gliosis 32 HP:0002171
20 global brain atrophy 32 HP:0002283
21 leukoencephalopathy 32 HP:0002352
22 developmental regression 32 HP:0002376
23 abnormal pyramidal signs 32 HP:0007256
24 severe demyelination of the white matter 32 HP:0007258
25 corpus callosum atrophy 32 HP:0007371
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:

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

Anatomical Context for L-2-Hydroxyglutaric Aciduria

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

41
Cerebellum, Brain, Liver

Publications for L-2-Hydroxyglutaric Aciduria

Articles related to L-2-Hydroxyglutaric Aciduria:

(show top 50) (show all 86)
# Title Authors Year
1
Manifestation of recessive combined D-2-, L-2-hydroxyglutaric aciduria in combination with 22q11.2 deletion syndrome. ( 29265763 )
2018
2
Muscle Weakness, Cardiomyopathy, and L-2-Hydroxyglutaric Aciduria Associated with a Novel Recessive SLC25A4 Mutation. ( 29654543 )
2018
3
A novel compound heterozygous mutation of the L2HGDH gene in a Chinese boy with L-2-hydroxyglutaric aciduria: case report and literature review. ( 29980873 )
2018
4
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
5
An overview of combined D-2- and L-2-hydroxyglutaric aciduria: functional analysis of CIC variants. ( 29238895 )
2017
6
An L-2-Hydroxyglutaric Aciduria Case Presented With Acute Bacterial Meningitis. ( 28141777 )
2017
7
Clinical features and disease progression of L-2-hydroxyglutaric aciduria in 27 Staffordshire bull terriers. ( 27729589 )
2016
8
In-vivo brain H1-MR-Spectroscopy identification and quantification of 2-hydroxyglutarate in L-2-Hydroxyglutaric aciduria. ( 27543339 )
2016
9
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
10
A novel compound heterozygous mutation in a Chinese boy with L-2-hydroxyglutaric aciduria: a case study. ( 26208971 )
2015
11
White matter abnormalities in an adult patient with l-2-hydroxyglutaric aciduria. ( 25982940 )
2015
12
A mouse model of L-2-hydroxyglutaric aciduria, a disorder of metabolite repair. ( 25763823 )
2015
13
Gliomatosis cerebri in L-2-hydroxyglutaric aciduria. ( 25997888 )
2015
14
L-2-Hydroxyglutaric aciduria: a case report. ( 25033591 )
2014
15
Successive distinct high-grade gliomas in L-2-hydroxyglutaric aciduria. ( 25338511 )
2014
16
Clinical, neuroimaging, and genetic features of L-2-hydroxyglutaric aciduria in Arab kindreds. ( 24894778 )
2014
17
Writer's cramp as a presentation of L-2-hydroxyglutaric aciduria. ( 26788335 )
2014
18
Founder effect confirmation of c.241A&amp;gt;G mutation in the L2HGDH gene and characterization of oxidative stress parameters in six Tunisian families with L-2-hydroxyglutaric aciduria. ( 24573090 )
2014
19
L-2-Hydroxyglutaric Aciduria: Report of Two Indian Families. ( 24037495 )
2013
20
Deficiency in SLC25A1, encoding the mitochondrial citrate carrier, causes combined D-2- and L-2-hydroxyglutaric aciduria. ( 23561848 )
2013
21
A L2HGDH initiator methionine codon mutation in a Yorkshire terrier with L-2-hydroxyglutaric aciduria. ( 22834903 )
2012
22
L-2-hydroxyglutaric aciduria in two female Yorkshire terriers. ( 22843824 )
2012
23
L-2-hydroxyglutaric aciduria diagnosed in a young adult with progressive cerebellar ataxia and facial dyskinesia. ( 22030381 )
2012
24
Clinical, genetic and magnetic resonance findings in an Italian patient affected by L-2-hydroxyglutaric aciduria. ( 20859647 )
2011
25
L-2-hydroxyglutaric aciduria and brain tumors. ( 20421813 )
2010
26
L-2-hydroxyglutaric aciduria: report of four Turkish adult patients. ( 20065797 )
2010
27
L-2-hydroxyglutaric aciduria and multiple acyl-coenzyme A dehydrogenase deficiency are distinct metabolic disorders. ( 20168250 )
2010
28
Wilms tumor in a child with L-2-hydroxyglutaric aciduria. ( 20064066 )
2010
29
L-2-hydroxyglutaric aciduria diagnosed in an adult presenting with acute deterioration. ( 19760480 )
2010
30
Riboflavin treatment in a case with l-2-hydroxyglutaric aciduria. ( 18343698 )
2009
31
A novel mutation as a cause of L-2-hydroxyglutaric aciduria. ( 19444541 )
2009
32
L-2-Hydroxyglutaric aciduria: pattern of MR imaging abnormalities in 56 patients. ( 19474378 )
2009
33
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
34
Sudden unexpected death in an infant with L-2-hydroxyglutaric aciduria. ( 19005678 )
2009
35
Tracing the origin of L-2-hydroxyglutaric aciduria in a family. ( 19863265 )
2009
36
Neuropathological findings in a Staffordshire bull terrier with l-2-hydroxyglutaric aciduria. ( 18295785 )
2008
37
Epilepsy in a young adult caused by L-2-hydroxyglutaric aciduria: a case report. ( 18408399 )
2008
38
A successfully treated adult patient with L-2-hydroxyglutaric aciduria. ( 18362286 )
2008
39
L-2-hydroxyglutaric aciduria: identification of ten novel mutations in the L2HGDH gene. ( 18415700 )
2008
40
L-2-hydroxyglutaric aciduria: clinical and molecular study in three Tunisian families. Identification of a new mutation and inter-familial phenotype variability. ( 18780161 )
2008
41
L-2-hydroxyglutaric aciduria and brain tumors in children with mutations in the L2HGDH gene: neuroimaging findings. ( 18671189 )
2008
42
L-2-Hydroxyglutaric aciduria presenting with severe autistic features. ( 17981416 )
2008
43
Mutation analysis a prerequisite for prenatal diagnosis of L-2-hydroxyglutaric aciduria? ( 17537659 )
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
L-2-hydroxyglutaric aciduria, a defect of metabolite repair. ( 17603759 )
2007
46
L-2-hydroxyglutaric aciduria: characterisation of the molecular defect in a spontaneous canine model. ( 17475916 )
2007
47
Osteoma of the calvaria in L-2-hydroxyglutaric aciduria. ( 17917788 )
2007
48
[L-2-hydroxyglutaric aciduria, an error of metabolism]. ( 18557388 )
2007
49
The gene mutated in L-2-hydroxyglutaric aciduria encodes L-2- hydroxyglutarate dehydrogenase. ( 16005139 )
2006
50
Hemiconvulsion-hemiplegia-epilepsy syndrome as a presenting feature of L-2-hydroxyglutaric aciduria. ( 16948946 )
2006

Variations for L-2-Hydroxyglutaric Aciduria

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

75
# 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 rs970541687
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
(show all 25)
# 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.905C> T (p.Pro302Leu) single nucleotide variant Pathogenic rs118204020 GRCh38 Chromosome 14, 50269164: 50269164
3 L2HGDH NM_024884.2(L2HGDH): c.1115delT (p.Met372Serfs) deletion Pathogenic rs786200869 GRCh37 Chromosome 14, 50732157: 50732157
4 L2HGDH NM_024884.2(L2HGDH): c.1115delT (p.Met372Serfs) deletion Pathogenic rs786200869 GRCh38 Chromosome 14, 50265439: 50265439
5 L2HGDH NM_024884.2(L2HGDH): c.906+1G> T single nucleotide variant Pathogenic rs786200870 GRCh37 Chromosome 14, 50735880: 50735880
6 L2HGDH NM_024884.2(L2HGDH): c.906+1G> T single nucleotide variant Pathogenic rs786200870 GRCh38 Chromosome 14, 50269162: 50269162
7 L2HGDH NM_024884.2(L2HGDH): c.164G> A (p.Gly55Asp) single nucleotide variant Pathogenic rs118204021 GRCh37 Chromosome 14, 50769712: 50769712
8 L2HGDH NM_024884.2(L2HGDH): c.164G> A (p.Gly55Asp) single nucleotide variant Pathogenic rs118204021 GRCh38 Chromosome 14, 50302994: 50302994
9 L2HGDH NC_000014.9: g.(50000000_?)_(?_50247254)del deletion Pathogenic GRCh38 Chromosome 14, 50000000: 50247254
10 L2HGDH NM_024884.2(L2HGDH): c.293A> G (p.His98Arg) single nucleotide variant Likely pathogenic rs267607206 GRCh37 Chromosome 14, 50768850: 50768850
11 L2HGDH NM_024884.2(L2HGDH): c.293A> G (p.His98Arg) single nucleotide variant Likely pathogenic rs267607206 GRCh38 Chromosome 14, 50302132: 50302132
12 L2HGDH NM_024884.2(L2HGDH): c.1003C> T (p.Arg335Ter) single nucleotide variant Pathogenic rs387907013 GRCh37 Chromosome 14, 50734532: 50734532
13 L2HGDH NM_024884.2(L2HGDH): c.1003C> T (p.Arg335Ter) single nucleotide variant Pathogenic rs387907013 GRCh38 Chromosome 14, 50267814: 50267814
14 L2HGDH NM_024884.2(L2HGDH): c.627A> G (p.Ala209=) single nucleotide variant Uncertain significance rs564306903 GRCh37 Chromosome 14, 50750665: 50750665
15 L2HGDH NM_024884.2(L2HGDH): c.627A> G (p.Ala209=) single nucleotide variant Uncertain significance rs564306903 GRCh38 Chromosome 14, 50283947: 50283947
16 L2HGDH NM_024884.2(L2HGDH): c.99G> T (p.Arg33Ser) single nucleotide variant Benign/Likely benign rs35710558 GRCh37 Chromosome 14, 50778770: 50778770
17 L2HGDH NM_024884.2(L2HGDH): c.99G> T (p.Arg33Ser) single nucleotide variant Benign/Likely benign rs35710558 GRCh38 Chromosome 14, 50312052: 50312052
18 L2HGDH NM_024884.2(L2HGDH): c.465delA (p.Gly156Alafs) deletion Pathogenic rs797045678 GRCh38 Chromosome 14, 50294190: 50294190
19 L2HGDH NM_024884.2(L2HGDH): c.465delA (p.Gly156Alafs) deletion Pathogenic rs797045678 GRCh37 Chromosome 14, 50760908: 50760908
20 L2HGDH NM_024884.2(L2HGDH): c.1015delA (p.Arg339Aspfs) deletion Pathogenic GRCh37 Chromosome 14, 50734520: 50734520
21 L2HGDH NM_024884.2(L2HGDH): c.1015delA (p.Arg339Aspfs) deletion Pathogenic GRCh38 Chromosome 14, 50267802: 50267802
22 L2HGDH NM_024884.2(L2HGDH): c.584A> G (p.Tyr195Cys) single nucleotide variant Likely pathogenic rs887386390 GRCh38 Chromosome 14, 50283990: 50283990
23 L2HGDH NM_024884.2(L2HGDH): c.584A> G (p.Tyr195Cys) single nucleotide variant Likely pathogenic rs887386390 GRCh37 Chromosome 14, 50750708: 50750708
24 L2HGDH NM_024884.2(L2HGDH): c.409-4G> T single nucleotide variant Likely benign rs767524925 GRCh38 Chromosome 14, 50294250: 50294250
25 L2HGDH NM_024884.2(L2HGDH): c.409-4G> T single nucleotide variant Likely benign rs767524925 GRCh37 Chromosome 14, 50760968: 50760968

Expression for L-2-Hydroxyglutaric Aciduria

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

Pathways for L-2-Hydroxyglutaric Aciduria

Pathways related to L-2-Hydroxyglutaric Aciduria according to KEGG:

37
# Name Kegg Source Accession
1 Butanoate metabolism hsa00650

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

# Super pathways Score Top Affiliating Genes
1
Show member pathways
10.74 L2HGDH MDH2

GO Terms for L-2-Hydroxyglutaric Aciduria

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

# Name GO ID Score Top Affiliating Genes
1 mitochondrion GO:0005739 9.26 GLS2 L2HGDH MDH2 SLC25A1
2 mitochondrial inner membrane GO:0005743 8.8 L2HGDH MDH2 SLC25A1

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

# 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
17 ExPASy
19 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 LOVD
42 MedGen
44 MeSH
45 MESH via Orphanet
46 MGI
49 NCI
50 NCIt
51 NDF-RT
54 NINDS
55 Novoseek
57 OMIM
58 OMIM via Orphanet
62 PubMed
64 QIAGEN
69 SNOMED-CT via HPO
70 SNOMED-CT via Orphanet
71 TGDB
72 Tocris
73 UMLS
74 UMLS via Orphanet
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