MCID: CMB040
MIFTS: 28

Combined D-2- and L-2-Hydroxyglutaric Aciduria

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

Aliases & Classifications for Combined D-2- and L-2-Hydroxyglutaric Aciduria

MalaCards integrated aliases for Combined D-2- and L-2-Hydroxyglutaric Aciduria:

Name: Combined D-2- and L-2-Hydroxyglutaric Aciduria 54 24 71 29 13 69
Combined D-2-Hydroxyglutaric Acidemia and L-2-Hydroxyglutaric Acidemia 56
Combined D-2-Hydroxyglutaric Aciduria and L-2-Hydroxyglutaric Aciduria 56
D,l-2-Hydroxyglutaric Aciduria 56
D,l-2-Hydroxyglutaric Acidemia 56
D,l-2-Hga 56
D2l2ad 71

Characteristics:

Orphanet epidemiological data:

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

OMIM:

54
Inheritance:
autosomal recessive

Miscellaneous:
onset in the neonatal period
death by age 3 years


HPO:

32
combined d-2- and l-2-hydroxyglutaric aciduria:
Inheritance autosomal recessive inheritance


Classifications:



Summaries for Combined D-2- and L-2-Hydroxyglutaric Aciduria

OMIM : 54
Combined D-2- and L-2-hydroxyglutaric aciduria (D-2-HG and L-2-HG) is an autosomal recessive neurometabolic disorder characterized by neonatal-onset encephalopathy with severe muscular weakness, intractable seizures, respiratory distress, and lack of psychomotor development resulting in early death. Brain imaging shows abnormalities including enlarged ventricles, delayed myelination, and germinal layer cysts (summary by Muntau et al., 2000). See also isolated L-2-hydroxyglutaric aciduria (236792) and isolated D-2-hydroxyglutaric aciduria (see 600721). (615182)

MalaCards based summary : Combined D-2- and L-2-Hydroxyglutaric Aciduria, also known as combined d-2-hydroxyglutaric acidemia and l-2-hydroxyglutaric acidemia, is related to l-2-hydroxyglutaric aciduria and 2-hydroxyglutaric aciduria, and has symptoms including ventriculomegaly, hepatomegaly and seizures. An important gene associated with Combined D-2- and L-2-Hydroxyglutaric Aciduria is SLC25A1 (Solute Carrier Family 25 Member 1). Affiliated tissues include brain and eye.

UniProtKB/Swiss-Prot : 71 Combined D-2- and L-2-hydroxyglutaric aciduria: An autosomal recessive neurometabolic disorder characterized by neonatal-onset encephalopathy with severe muscular weakness, intractable seizures, respiratory distress, and lack of psychomotor development resulting in early death. Brain imaging shows abnormalities including enlarged ventricles, delayed myelination, and germinal layer cysts.

Related Diseases for Combined D-2- and L-2-Hydroxyglutaric Aciduria

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

id Related Disease Score Top Affiliating Genes
1 l-2-hydroxyglutaric aciduria 10.3
2 2-hydroxyglutaric aciduria 10.1
3 encephalopathy 10.1

Symptoms & Phenotypes for Combined D-2- and L-2-Hydroxyglutaric Aciduria

Symptoms via clinical synopsis from OMIM:

54

Neurologic- Central Nervous System:
seizures
lack of psychomotor development
irritability
cerebellar hypoplasia
encephalopathy
more
Head And Neck- Eyes:
poor eye contact
cortical blindness (1 patient)

Respiratory:
dyspnea
respiratory insufficiency
stridor

Head And Neck- Head:
macrocephaly (1 patient)
microcephaly (1 patient)

Abdomen- Gastroin testinal:
poor feeding

Muscle Soft Tissue:
hypotonia, severe

Abdomen- Liver:
hepatomegaly (1 patient)

Laboratory- Abnormalities:
increased urinary, plasma, and csf d-2-hydroxyglutaric acid
increased urinary, plasma, and csf l-2-hydroxyglutaric acid
predominance of the d-stereoisomer
increased urinary 2-oxoglutaric acid


Clinical features from OMIM:

615182

Human phenotypes related to Combined D-2- and L-2-Hydroxyglutaric Aciduria:

32 (show all 18)
id Description HPO Frequency HPO Source Accession
1 ventriculomegaly 32 HP:0002119
2 hepatomegaly 32 occasional (7.5%) HP:0002240
3 seizures 32 HP:0001250
4 microcephaly 32 occasional (7.5%) HP:0000252
5 poor eye contact 32 HP:0000817
6 irritability 32 HP:0000737
7 cerebellar hypoplasia 32 HP:0001321
8 encephalopathy 32 HP:0001298
9 global developmental delay 32 HP:0001263
10 cortical visual impairment 32 occasional (7.5%) HP:0100704
11 macrocephaly 32 occasional (7.5%) HP:0000256
12 delayed myelination 32 HP:0012448
13 dyspnea 32 HP:0002094
14 respiratory insufficiency 32 HP:0002093
15 feeding difficulties 32 HP:0011968
16 stridor 32 HP:0010307
17 severe muscular hypotonia 32 HP:0006829
18 l-2-hydroxyglutaric aciduria 32 HP:0040144

UMLS symptoms related to Combined D-2- and L-2-Hydroxyglutaric Aciduria:


dyspnea, seizures, stridor

Drugs & Therapeutics for Combined D-2- and L-2-Hydroxyglutaric Aciduria

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

Genetic Tests for Combined D-2- and L-2-Hydroxyglutaric Aciduria

Genetic tests related to Combined D-2- and L-2-Hydroxyglutaric Aciduria:

id Genetic test Affiliating Genes
1 Combined D-2- and L-2-Hydroxyglutaric Aciduria 29 24 SLC25A1

Anatomical Context for Combined D-2- and L-2-Hydroxyglutaric Aciduria

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

39
Brain, Eye

Publications for Combined D-2- and L-2-Hydroxyglutaric Aciduria

Articles related to Combined D-2- and L-2-Hydroxyglutaric Aciduria:

id Title Authors Year
1
Deficiency in SLC25A1, encoding the mitochondrial citrate carrier, causes combined D-2- and L-2-hydroxyglutaric aciduria. ( 23561848 )
2013
2
Combined D-2- and L-2-hydroxyglutaric aciduria with neonatal onset encephalopathy: a third biochemical variant of 2-hydroxyglutaric aciduria? ( 10963100 )
2000

Variations for Combined D-2- and L-2-Hydroxyglutaric Aciduria

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

71
id Symbol AA change Variation ID SNP ID
1 SLC25A1 p.Pro45Leu VAR_069490
2 SLC25A1 p.Glu144Gln VAR_069491
3 SLC25A1 p.Gly167Arg VAR_069492
4 SLC25A1 p.Ser193Trp VAR_069493 rs781925968
5 SLC25A1 p.Met202Thr VAR_069494 rs782335811
6 SLC25A1 p.Arg282Cys VAR_069495 rs431905509
7 SLC25A1 p.Arg282Gly VAR_069496 rs431905509
8 SLC25A1 p.Tyr297Cys VAR_069497
9 SLC25A1 p.Arg198His VAR_077511

ClinVar genetic disease variations for Combined D-2- and L-2-Hydroxyglutaric Aciduria:

6
id Gene Variation Type Significance SNP ID Assembly Location
1 SLC25A1 NM_005984.4(SLC25A1): c.844C> G (p.Arg282Gly) single nucleotide variant Pathogenic rs431905509 GRCh37 Chromosome 22, 19163735: 19163735
2 SLC25A1 NM_005984.4(SLC25A1): c.844C> T (p.Arg282Cys) single nucleotide variant Pathogenic rs431905509 GRCh37 Chromosome 22, 19163735: 19163735
3 SLC25A1 NM_005984.4(SLC25A1): c.845G> A (p.Arg282His) single nucleotide variant Pathogenic rs431905510 GRCh37 Chromosome 22, 19163734: 19163734
4 SLC25A1 NM_005984.4(SLC25A1): c.389G> A (p.Gly130Asp) single nucleotide variant Pathogenic rs368647424 GRCh37 Chromosome 22, 19165292: 19165292
5 SLC25A1 NM_005984.4(SLC25A1): c.821C> T (p.Ala274Val) single nucleotide variant Pathogenic rs483352910 GRCh37 Chromosome 22, 19163934: 19163934
6 SLC25A1 NM_005984.4(SLC25A1): c.517_526delCGGGAACAAG (p.Arg173Glyfs) deletion Pathogenic rs483352911 GRCh37 Chromosome 22, 19164633: 19164642

Expression for Combined D-2- and L-2-Hydroxyglutaric Aciduria

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

Pathways for Combined D-2- and L-2-Hydroxyglutaric Aciduria

GO Terms for Combined D-2- and L-2-Hydroxyglutaric Aciduria

Sources for Combined D-2- and 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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