D2L2AD
MCID: CMB040
MIFTS: 30

Combined D-2- and L-2-Hydroxyglutaric Aciduria (D2L2AD)

Categories: Genetic diseases, Metabolic diseases, Muscle diseases, Neuronal 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 57 74 37 29 13 6 72
D2l2ad 57 74
Combined D-2-Hydroxyglutaric Acidemia and L-2-Hydroxyglutaric Acidemia 59
Combined D-2-Hydroxyglutaric Aciduria and L-2-Hydroxyglutaric Aciduria 59
D,l-2-Hydroxyglutaric Aciduria 59
D,l-2-Hydroxyglutaric Acidemia 59
D,l-2-Hga 59

Characteristics:

Orphanet epidemiological data:

59
d,l-2-hydroxyglutaric aciduria
Inheritance: Autosomal recessive; Prevalence: <1/1000000 (Worldwide); Age of onset: Infancy,Neonatal;

OMIM:

57
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:



External Ids:

OMIM 57 615182
KEGG 37 H02304
MeSH 44 D020739
ICD10 via Orphanet 34 E72.8
Orphanet 59 ORPHA356978
MedGen 42 C2746066
UMLS 72 C2746066

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

OMIM : 57 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 d2l2ad, is related to l-2-hydroxyglutaric aciduria and 2-hydroxyglutaric aciduria, and has symptoms including seizures, dyspnea and stridor. 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, and related phenotypes are macrocephaly and hepatomegaly

KEGG : 37
Combined D-2- and L-2-hydroxyglutaric aciduria (D,L-2-HGA), characterized by elevated levels of both D-2-hydroxyglutarate (HG) and L-2-HG in body fluids, mainly manifests in a severe neonatal epileptic encephalopathy, absence of developmental progress, and often early death. Recessive mutations in SLC25A1, the mitochondrial citrate carrier, have been reported in individuals with D,L-2-HGA.

UniProtKB/Swiss-Prot : 74 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:

# Related Disease Score Top Affiliating Genes
1 l-2-hydroxyglutaric aciduria 12.1
2 2-hydroxyglutaric aciduria 12.1
3 d-2-hydroxyglutaric aciduria 1 12.0
4 encephalopathy 10.4
5 neurometabolic disease 10.4
6 lactic acidosis 10.3
7 inherited metabolic disorder 10.3

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



Diseases related to Combined D-2- and L-2-Hydroxyglutaric Aciduria

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

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

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

Symptoms via clinical synopsis from OMIM:

57
Neurologic Central Nervous System:
seizures
irritability
cerebellar hypoplasia
encephalopathy
delayed myelination
more
Head And Neck Eyes:
poor eye contact
cortical blindness (1 patient)

Muscle Soft Tissue:
hypotonia, severe

Abdomen Liver:
hepatomegaly (1 patient)

Respiratory:
respiratory insufficiency
dyspnea
stridor

Abdomen Gastrointestinal:
poor feeding

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

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


seizures, dyspnea, 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:

# Genetic test Affiliating Genes
1 Combined D-2- and L-2-Hydroxyglutaric Aciduria 29 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:

41
Brain, Eye

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

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

# Title Authors PMID Year
1
Deficiency in SLC25A1, encoding the mitochondrial citrate carrier, causes combined D-2- and L-2-hydroxyglutaric aciduria. 38 8 71
23561848 2013
2
Agenesis of corpus callosum and optic nerve hypoplasia due to mutations in SLC25A1 encoding the mitochondrial citrate transporter. 8 71
23393310 2013
3
Combined D-2- and L-2-hydroxyglutaric aciduria with neonatal onset encephalopathy: a third biochemical variant of 2-hydroxyglutaric aciduria? 38 8
10963100 2000
4
Mutations in the Mitochondrial Citrate Carrier SLC25A1 are Associated with Impaired Neuromuscular Transmission. 8
26870663 2014
5
A Drosophila model of combined D-2- and L-2-hydroxyglutaric aciduria reveals a mechanism linking mitochondrial citrate export with oncometabolite accumulation. 38
30108060 2018
6
An overview of combined D-2- and L-2-hydroxyglutaric aciduria: functional analysis of CIC variants. 38
29238895 2018
7
Manifestation of recessive combined D-2-, L-2-hydroxyglutaric aciduria in combination with 22q11.2 deletion syndrome. 38
29265763 2018
8
Severe Neonatal Presentation of Mitochondrial Citrate Carrier (SLC25A1) Deficiency. 38
27306203 2016

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

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

6
# Gene Variation Type Significance SNP ID GRCh37 Pos GRCh38 Pos
1 SLC25A1 NM_005984.5(SLC25A1): c.821C> T (p.Ala274Val) single nucleotide variant Pathogenic rs483352910 22:19163934-19163934 22:19176421-19176421
2 SLC25A1 NM_005984.5(SLC25A1): c.389G> A (p.Gly130Asp) single nucleotide variant Pathogenic rs368647424 22:19165292-19165292 22:19177779-19177779
3 SLC25A1 NM_005984.5(SLC25A1): c.845G> A (p.Arg282His) single nucleotide variant Pathogenic rs431905510 22:19163734-19163734 22:19176221-19176221
4 SLC25A1 NM_005984.5(SLC25A1): c.844C> T (p.Arg282Cys) single nucleotide variant Pathogenic rs431905509 22:19163735-19163735 22:19176222-19176222
5 SLC25A1 NM_005984.5(SLC25A1): c.844C> G (p.Arg282Gly) single nucleotide variant Pathogenic rs431905509 22:19163735-19163735 22:19176222-19176222
6 SLC25A1 NM_005984.5(SLC25A1): c.517_526del (p.Arg173fs) deletion Likely pathogenic rs483352911 22:19164633-19164642 22:19177120-19177129

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

74 (show all 15)
# 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 rs133141701
10 SLC25A1 p.Ile40Asn VAR_081662
11 SLC25A1 p.Gly93Asp VAR_081664
12 SLC25A1 p.Gly130Asp VAR_081665 rs368647424
13 SLC25A1 p.Asn238Ser VAR_081666
14 SLC25A1 p.Cys262Arg VAR_081669
15 SLC25A1 p.Arg282His VAR_081670 rs431905510

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
17 EFO
18 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 TGDB
71 Tocris
72 UMLS
73 UMLS via Orphanet
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