D,L-2-hydroxyglutaric aciduria

General Information (adopted from Orphanet):

Synonyms, Signs: D2L2AD
D,L-2-HGA
Combined D-2-hydroxyglutaric aciduria and L-2-hydroxyglutaric aciduria
Combined D-2-hydroxyglutaric acidemia and L-2-hydroxyglutaric acidemia
D,L-2-hydroxyglutaric acidemia
Number of Symptoms 28
OrphanetNr: 356978
OMIM Id: 615182
ICD-10: E72.8
UMLs:
MeSH:
MedDRA:
Snomed:

Prevalence, inheritance and age of onset:

Prevalence: No data available.
Inheritance: Autosomal recessive
[Orphanet]
Age of onset: Neonatal
Infancy
[Orphanet]

Disease classification (adopted from Orphanet):

Parent Diseases: 2-hydroxyglutaric aciduria
 -Rare genetic disease
 -Rare neurologic disease

Symptom Information: Sort by abundance 

1
 (HPO:0000252) Microcephaly rare [HPO:skoehler] 832 / 7739
2
 (HPO:0000256) Macrocephaly rare [HPO:skoehler] 298 / 7739
3
 (HPO:0004482) Relative macrocephaly 44 / 7739
4
 (HPO:0100704) Cortical visual impairment rare [HPO:skoehler] 28 / 7739
5
 (HPO:0001298) Encephalopathy 72 / 7739
6
 (HPO:0000737) Irritability 93 / 7739
7
 (HPO:0000817) Poor eye contact 26 / 7739
8
 (HPO:0001250) Seizures 1245 / 7739
9
 (HPO:0001263) Global developmental delay 853 / 7739
10
 (HPO:0011968) Feeding difficulties 240 / 7739
11
 (HPO:0002240) Hepatomegaly rare [HPO:skoehler] 467 / 7739
12
 (HPO:0002094) Dyspnea 132 / 7739
13
 (HPO:0010307) Stridor 19 / 7739
14
 (HPO:0002093) Respiratory insufficiency 410 / 7739
15
 (HPO:0006829) Severe muscular hypotonia 29 / 7739
16
 (HPO:0040144) L-2-hydroxyglutaric aciduria 3 / 7739
17
 (OMIM) Increased urinary 2-oxoglutaric acid 1 / 7739
18
 (OMIM) Germinal cysts over the caudate 1 / 7739
19
 (HPO:0000007) Autosomal recessive inheritance 2538 / 7739
20
 (OMIM) Delayed opercularization 1 / 7739
21
 (OMIM) Increased urinary, plasma, and CSF D-2-hydroxyglutaric acid 1 / 7739
22
 (OMIM) Increased urinary, plasma, and CSF L-2-hydroxyglutaric acid 1 / 7739
23
 (HPO:0002119) Ventriculomegaly 253 / 7739
24
 (OMIM) Predominance of the D-stereoisomer 1 / 7739
25
 (HPO:0001355) Megalencephaly 39 / 7739
26
 (HPO:0001321) Cerebellar hypoplasia 114 / 7739
27
 (HPO:0012448) Delayed myelination 51 / 7739
28
 (OMIM) Delayed gyration 2 / 7739

Associated genes:

ClinVar (via SNiPA)

Gene symbol Variation Clinical significance Reference

Additional Information:

Description: (OMIM) 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 ...
Clinical Description OMIM Muntau et al. (2000) reported 3 patients, including 2 sibs, with severe neonatal encephalopathy associated with combined D-2- and L-2-hydroxyglutaric aciduria. The first patient presented in the neonatal period with hypotonia, irritability, uncontrollable seizures, poor eye contact, and ...
Molecular genetics OMIM Nota et al. (2013) identified missense, nonsense, and frameshift mutations in homozygosity and compound heterozygosity in 12 patients with combined D-2- and L-2-hydroxyglutaric aciduria (e.g., 190315.0001, 190315.0002).

The patient described by Edvardson et al. (2013) was ...