MCID: L2H001
MIFTS: 43

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 53 12 49 55 71 36 28 13 14 69
L-2-Hydroxyglutaric Acidemia 53 12 49 55 71 28 69
L2hga 53 71
Combined D-2- and L-2-Hydroxyglutaric Aciduria 69
L-2-Hga 55

Characteristics:

Orphanet epidemiological data:

55
l-2-hydroxyglutaric aciduria
Inheritance: Autosomal recessive; Prevalence: <1/1000000 (Worldwide); Age of onset: Childhood; Age of death: normal life expectancy;

OMIM:

53
Inheritance:
autosomal recessive

Miscellaneous:
onset in infancy or early childhood


HPO:

31
l-2-hydroxyglutaric aciduria:
Onset and clinical course infantile onset
Inheritance autosomal recessive inheritance


Classifications:



Summaries for L-2-Hydroxyglutaric Aciduria

NIH Rare Diseases : 49 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 2-hydroxyglutaric aciduria and d-2-hydroxyglutaric aciduria 1, and has symptoms including seizures, abnormality of extrapyramidal motor function and macrocephaly. 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.

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.

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 22)
# Related Disease Score Top Affiliating Genes
1 2-hydroxyglutaric aciduria 32.5 L2HGDH MDH2 SLC25A1
2 d-2-hydroxyglutaric aciduria 1 31.6 GLS2 L2HGDH
3 combined d-2- and l-2-hydroxyglutaric aciduria 12.6
4 encephalopathy 10.2
5 epilepsy 10.1
6 medulloblastoma 10.0
7 migraine with or without aura 1 10.0
8 ataxia and polyneuropathy, adult-onset 10.0
9 wilms tumor 5 10.0
10 aceruloplasminemia 10.0
11 ataxia-oculomotor apraxia 3 10.0
12 wilms tumor 6 10.0
13 hemiplegia 10.0
14 status epilepticus 10.0
15 lactic acidosis 10.0
16 gliomatosis cerebri 10.0
17 bacterial meningitis 10.0
18 meningitis 10.0
19 glioma 10.0
20 tremor 10.0
21 idiopathic hemiconvulsion-hemiplegia syndrome 10.0
22 velocardiofacial syndrome 9.6 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:

53
Neurologic Central Nervous System:
seizures
dysphasia
spastic tetraparesis
extrapyramidal signs
pyramidal signs
more
Head And Neck Ears:
hearing loss

Head And Neck Eyes:
nystagmus
optic atrophy
strabismus

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:

55 31 (show all 27)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 seizures 55 31 hallmark (90%) Very frequent (99-80%) HP:0001250
2 abnormality of extrapyramidal motor function 55 31 frequent (33%) Frequent (79-30%) HP:0002071
3 macrocephaly 55 31 frequent (33%) Frequent (79-30%) HP:0000256
4 muscular hypotonia 55 31 frequent (33%) Frequent (79-30%) HP:0001252
5 dysphasia 55 31 occasional (7.5%) Occasional (29-5%) HP:0002357
6 encephalitis 55 31 hallmark (90%) Very frequent (99-80%) HP:0002383
7 behavioral abnormality 55 31 frequent (33%) Frequent (79-30%) HP:0000708
8 intellectual disability, severe 55 31 hallmark (90%) Very frequent (99-80%) HP:0010864
9 aplasia/hypoplasia of the cerebellum 55 31 frequent (33%) Frequent (79-30%) HP:0007360
10 intellectual disability, progressive 55 31 hallmark (90%) Very frequent (99-80%) HP:0006887
11 neoplasm of the nervous system 55 31 frequent (33%) Frequent (79-30%) HP:0004375
12 spastic tetraparesis 55 31 frequent (33%) Frequent (79-30%) HP:0001285
13 abnormal pyramidal signs 31 HP:0007256
14 nystagmus 31 HP:0000639
15 developmental regression 31 HP:0002376
16 hearing impairment 31 HP:0000365
17 optic atrophy 31 HP:0000648
18 strabismus 31 HP:0000486
19 cerebellar atrophy 31 HP:0001272
20 gliosis 31 HP:0002171
21 global brain atrophy 31 HP:0002283
22 leukoencephalopathy 31 HP:0002352
23 corpus callosum atrophy 31 HP:0007371
24 severe demyelination of the white matter 31 HP:0007258
25 morphological abnormality of the pyramidal tract 31 HP:0002062
26 l-2-hydroxyglutaric aciduria 31 HP:0040144
27 l-2-hydroxyglutaric acidemia 31 HP:0040147

UMLS symptoms related to L-2-Hydroxyglutaric Aciduria:


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

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 28 L2HGDH
2 L-2-Hydroxyglutaric Acidemia 28

Anatomical Context for L-2-Hydroxyglutaric Aciduria

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

38
Cerebellum, Brain, Liver

Publications for L-2-Hydroxyglutaric Aciduria

Articles related to L-2-Hydroxyglutaric Aciduria:

(show top 50) (show all 84)
# Title Authors Year
1
Manifestation of recessive combined D-2-, L-2-hydroxyglutaric aciduria in combination with 22q11.2 deletion syndrome. ( 29265763 )
2018
2
An overview of combined D-2- and L-2-hydroxyglutaric aciduria: functional analysis of CIC variants. ( 29238895 )
2017
3
An L-2-Hydroxyglutaric Aciduria Case Presented With Acute Bacterial Meningitis. ( 28141777 )
2017
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
In-vivo brain H1-MR-Spectroscopy identification and quantification of 2-hydroxyglutarate in L-2-Hydroxyglutaric aciduria. ( 27543339 )
2016
6
Clinical features and disease progression of L-2-hydroxyglutaric aciduria in 27 Staffordshire bull terriers. ( 27729589 )
2016
7
Gliomatosis cerebri in L-2-hydroxyglutaric aciduria. ( 25997888 )
2015
8
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
9
A mouse model of L-2-hydroxyglutaric aciduria, a disorder of metabolite repair. ( 25763823 )
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
L-2-Hydroxyglutaric aciduria: a case report. ( 25033591 )
2014
13
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
14
Successive distinct high-grade gliomas in L-2-hydroxyglutaric aciduria. ( 25338511 )
2014
15
Writer's cramp as a presentation of L-2-hydroxyglutaric aciduria. ( 26788335 )
2014
16
Clinical, neuroimaging, and genetic features of L-2-hydroxyglutaric aciduria in Arab kindreds. ( 24894778 )
2014
17
Deficiency in SLC25A1, encoding the mitochondrial citrate carrier, causes combined D-2- and L-2-hydroxyglutaric aciduria. ( 23561848 )
2013
18
L-2-Hydroxyglutaric Aciduria: Report of Two Indian Families. ( 24037495 )
2013
19
L-2-hydroxyglutaric aciduria diagnosed in a young adult with progressive cerebellar ataxia and facial dyskinesia. ( 22030381 )
2012
20
A L2HGDH initiator methionine codon mutation in a Yorkshire terrier with L-2-hydroxyglutaric aciduria. ( 22834903 )
2012
21
L-2-hydroxyglutaric aciduria in two female Yorkshire terriers. ( 22843824 )
2012
22
Clinical, genetic and magnetic resonance findings in an Italian patient affected by L-2-hydroxyglutaric aciduria. ( 20859647 )
2011
23
L-2-hydroxyglutaric aciduria and brain tumors. ( 20421813 )
2010
24
L-2-hydroxyglutaric aciduria diagnosed in an adult presenting with acute deterioration. ( 19760480 )
2010
25
Wilms tumor in a child with L-2-hydroxyglutaric aciduria. ( 20064066 )
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
Riboflavin treatment in a case with l-2-hydroxyglutaric aciduria. ( 18343698 )
2009
29
Sudden unexpected death in an infant with L-2-hydroxyglutaric aciduria. ( 19005678 )
2009
30
L-2-Hydroxyglutaric aciduria: pattern of MR imaging abnormalities in 56 patients. ( 19474378 )
2009
31
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
32
Tracing the origin of L-2-hydroxyglutaric aciduria in a family. ( 19863265 )
2009
33
A novel mutation as a cause of L-2-hydroxyglutaric aciduria. ( 19444541 )
2009
34
Neuropathological findings in a Staffordshire bull terrier with l-2-hydroxyglutaric aciduria. ( 18295785 )
2008
35
L-2-hydroxyglutaric aciduria: clinical and molecular study in three Tunisian families. Identification of a new mutation and inter-familial phenotype variability. ( 18780161 )
2008
36
Epilepsy in a young adult caused by L-2-hydroxyglutaric aciduria: a case report. ( 18408399 )
2008
37
L-2-Hydroxyglutaric aciduria presenting with severe autistic features. ( 17981416 )
2008
38
L-2-hydroxyglutaric aciduria and brain tumors in children with mutations in the L2HGDH gene: neuroimaging findings. ( 18671189 )
2008
39
A successfully treated adult patient with L-2-hydroxyglutaric aciduria. ( 18362286 )
2008
40
L-2-hydroxyglutaric aciduria: identification of ten novel mutations in the L2HGDH gene. ( 18415700 )
2008
41
L-2-hydroxyglutaric aciduria: characterisation of the molecular defect in a spontaneous canine model. ( 17475916 )
2007
42
Mutation analysis a prerequisite for prenatal diagnosis of L-2-hydroxyglutaric aciduria? ( 17537659 )
2007
43
L-2-hydroxyglutaric aciduria, a defect of metabolite repair. ( 17603759 )
2007
44
[L-2-hydroxyglutaric aciduria, an error of metabolism]. ( 18557388 )
2007
45
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
46
Osteoma of the calvaria in L-2-hydroxyglutaric aciduria. ( 17917788 )
2007
47
The gene mutated in L-2-hydroxyglutaric aciduria encodes L-2- hydroxyglutarate dehydrogenase. ( 16005139 )
2006
48
L-2-Hydroxyglutaric aciduria: clinical, genetic, and brain MRI characteristics in two adult sisters. ( 16722976 )
2006
49
Hemiconvulsion-hemiplegia-epilepsy syndrome as a presenting feature of L-2-hydroxyglutaric aciduria. ( 16948946 )
2006
50
Normal pregnancy outcome in L-2-hydroxyglutaric aciduria. ( 16802109 )
2006

Variations for L-2-Hydroxyglutaric Aciduria

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

71
# 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
# Gene Variation Type Significance SNP ID Assembly Location
1 L2HGDH NM_024884.2(L2HGDH): c.1003C> T (p.Arg335Ter) single nucleotide variant Pathogenic rs387907013 GRCh37 Chromosome 14, 50734532: 50734532
2 L2HGDH NM_024884.2(L2HGDH): c.906+1G> T single nucleotide variant Pathogenic rs786200870 GRCh38 Chromosome 14, 50269162: 50269162
3 L2HGDH NM_024884.2(L2HGDH): c.1115delT (p.Met372Serfs) deletion Pathogenic rs786200869 GRCh38 Chromosome 14, 50265439: 50265439
4 L2HGDH NM_024884.2(L2HGDH): c.905C> T (p.Pro302Leu) single nucleotide variant Pathogenic rs118204020 GRCh37 Chromosome 14, 50735882: 50735882
5 L2HGDH NM_024884.2(L2HGDH): c.164G> A (p.Gly55Asp) single nucleotide variant Pathogenic rs118204021 GRCh37 Chromosome 14, 50769712: 50769712
6 L2HGDH NC_000014.9: g.(50000000_?)_(?_50247254)del deletion Pathogenic GRCh38 Chromosome 14, 50000000: 50247254
7 L2HGDH NM_024884.2(L2HGDH): c.293A> G (p.His98Arg) single nucleotide variant Pathogenic/Likely pathogenic rs267607206 GRCh37 Chromosome 14, 50768850: 50768850
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

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

36
# 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
16 ExPASy
18 FMA
27 GO
28 GTR
29 HGMD
30 HMDB
31 HPO
32 ICD10
33 ICD10 via Orphanet
34 ICD9CM
35 IUPHAR
36 KEGG
37 LifeMap
39 MedGen
41 MeSH
42 MESH via Orphanet
43 MGI
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47 NDF-RT
50 NINDS
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53 OMIM
54 OMIM via Orphanet
58 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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