CSGD
MCID: GLT011
MIFTS: 26

Glutamine Deficiency, Congenital (CSGD)

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

Aliases & Classifications for Glutamine Deficiency, Congenital

MalaCards integrated aliases for Glutamine Deficiency, Congenital:

Name: Glutamine Deficiency, Congenital 58 54 76 30 13 6 41 74
Glutamine Synthase Deficiency, Congenital Systemic 58 76
Congenital Systemic Glutamine Deficiency 76 38
Congenital Brain Dysgenesis Due to Glutamine Synthetase Deficiency 60
Glutamine Synthetase Deficiency, Congenital Systemic 54
Inherited Glutamine Synthetase Deficiency 60
Congenital Glutamine Deficiency 54
Inherited Gs Deficiency 60
Csgd 76

Characteristics:

Orphanet epidemiological data:

60
congenital brain dysgenesis due to glutamine synthetase deficiency
Inheritance: Autosomal recessive; Prevalence: <1/1000000 (Worldwide); Age of onset: Infancy,Neonatal;

OMIM:

58
Inheritance:
autosomal recessive

Miscellaneous:
onset as neonate
three patients have been reported
death in infancy in 2 patients
variable severity of brain malformations


HPO:

33
glutamine deficiency, congenital:
Clinical modifier death in infancy
Inheritance autosomal recessive inheritance


Classifications:



Summaries for Glutamine Deficiency, Congenital

OMIM : 58 Congenital glutamine deficiency is a severe autosomal recessive disorder characterized by onset at birth of encephalopathy, lack of normal development, seizures, and hypotonia associated with variable brain abnormalities (summary by Haberle et al., 2011). (610015)

MalaCards based summary : Glutamine Deficiency, Congenital, also known as glutamine synthase deficiency, congenital systemic, is related to mast cell activation syndrome, and has symptoms including seizures and apnea. An important gene associated with Glutamine Deficiency, Congenital is GLUL (Glutamate-Ammonia Ligase), and among its related pathways/superpathways are Alanine, aspartate and glutamate metabolism and Arginine biosynthesis. Affiliated tissues include brain, skin and cerebellum, and related phenotypes are flexion contracture and micromelia

UniProtKB/Swiss-Prot : 76 Congenital systemic glutamine deficiency: Rare developmental disorder with severe brain malformation resulting in multi-organ failure and neonatal death. Glutamine is largely absent from affected patients serum, urine and cerebrospinal fluid.

Related Diseases for Glutamine Deficiency, Congenital

Diseases related to Glutamine Deficiency, Congenital via text searches within MalaCards or GeneCards Suite gene sharing:

# Related Disease Score Top Affiliating Genes
1 mast cell activation syndrome 10.2

Symptoms & Phenotypes for Glutamine Deficiency, Congenital

Human phenotypes related to Glutamine Deficiency, Congenital:

33 (show all 21)
# Description HPO Frequency HPO Source Accession
1 flexion contracture 33 occasional (7.5%) HP:0001371
2 micromelia 33 occasional (7.5%) HP:0002983
3 low-set ears 33 HP:0000369
4 brain atrophy 33 HP:0012444
5 seizures 33 HP:0001250
6 hyperreflexia 33 HP:0001347
7 respiratory insufficiency 33 HP:0002093
8 depressed nasal bridge 33 HP:0005280
9 wide nasal bridge 33 HP:0000431
10 severe global developmental delay 33 HP:0011344
11 apnea 33 HP:0002104
12 ventriculomegaly 33 HP:0002119
13 skin rash 33 HP:0000988
14 hyperammonemia 33 HP:0001987
15 generalized hypotonia 33 HP:0001290
16 encephalopathy 33 HP:0001298
17 hypoplasia of the corpus callosum 33 HP:0002079
18 cns hypomyelination 33 HP:0003429
19 bradycardia 33 HP:0001662
20 subependymal cysts 33 HP:0002416
21 periventricular cysts 33 HP:0007109

Symptoms via clinical synopsis from OMIM:

58
Head And Neck Ears:
low-set ears

Respiratory:
respiratory insufficiency
apnea

Cardiovascular Heart:
bradycardia

Skeletal:
contractures (1 patient)

Skin Nails Hair Skin:
blistering erythematous rash

Neurologic Central Nervous System:
brain atrophy
seizures
hyperreflexia
ventriculomegaly
encephalopathy
more
Laboratory Abnormalities:
hyperammonemia
decreased glutamine in bodily fluids

Head And Neck Nose:
flat, broad nasal root

Skeletal Limbs:
micromelia (1 patient)

Skin Nails Hair Skin Histology:
necrotic epidermolysis

Clinical features from OMIM:

610015

UMLS symptoms related to Glutamine Deficiency, Congenital:


seizures, apnea

Drugs & Therapeutics for Glutamine Deficiency, Congenital

Search Clinical Trials , NIH Clinical Center for Glutamine Deficiency, Congenital

Genetic Tests for Glutamine Deficiency, Congenital

Genetic tests related to Glutamine Deficiency, Congenital:

# Genetic test Affiliating Genes
1 Glutamine Deficiency, Congenital 30 GLUL

Anatomical Context for Glutamine Deficiency, Congenital

MalaCards organs/tissues related to Glutamine Deficiency, Congenital:

42
Brain, Skin, Cerebellum

Publications for Glutamine Deficiency, Congenital

Articles related to Glutamine Deficiency, Congenital:

# Title Authors Year
1
Natural course of glutamine synthetase deficiency in a 3 year old patient. ( 21353613 )
2011
2
Congenital glutamine deficiency with glutamine synthetase mutations. ( 16267323 )
2005

Variations for Glutamine Deficiency, Congenital

UniProtKB/Swiss-Prot genetic disease variations for Glutamine Deficiency, Congenital:

76
# Symbol AA change Variation ID SNP ID
1 GLUL p.Arg324Cys VAR_026560 rs80358214
2 GLUL p.Arg341Cys VAR_026561 rs80358215

ClinVar genetic disease variations for Glutamine Deficiency, Congenital:

6 (show top 50) (show all 192)
# Gene Variation Type Significance SNP ID Assembly Location
1 GLUL NM_002065.6(GLUL): c.970C> T (p.Arg324Cys) single nucleotide variant Pathogenic rs80358214 GRCh37 Chromosome 1, 182353692: 182353692
2 GLUL NM_002065.6(GLUL): c.970C> T (p.Arg324Cys) single nucleotide variant Pathogenic rs80358214 GRCh38 Chromosome 1, 182384557: 182384557
3 GLUL NM_002065.6(GLUL): c.1021C> T (p.Arg341Cys) single nucleotide variant Pathogenic rs80358215 GRCh37 Chromosome 1, 182353641: 182353641
4 GLUL NM_002065.6(GLUL): c.1021C> T (p.Arg341Cys) single nucleotide variant Pathogenic rs80358215 GRCh38 Chromosome 1, 182384506: 182384506
5 GLUL NM_002065.6(GLUL): c.970C> A (p.Arg324Ser) single nucleotide variant Pathogenic rs80358214 GRCh37 Chromosome 1, 182353692: 182353692
6 GLUL NM_002065.6(GLUL): c.970C> A (p.Arg324Ser) single nucleotide variant Pathogenic rs80358214 GRCh38 Chromosome 1, 182384557: 182384557
7 GLUL NM_002065.6(GLUL): c.*1364G> A single nucleotide variant Likely benign rs115448180 GRCh38 Chromosome 1, 182383041: 182383041
8 GLUL NM_002065.6(GLUL): c.*1364G> A single nucleotide variant Likely benign rs115448180 GRCh37 Chromosome 1, 182352176: 182352176
9 GLUL NM_002065.6(GLUL): c.-304G> A single nucleotide variant Likely benign rs192236496 GRCh37 Chromosome 1, 182359922: 182359922
10 GLUL NM_002065.6(GLUL): c.*2644G> C single nucleotide variant Benign rs2296523 GRCh38 Chromosome 1, 182381761: 182381761
11 GLUL NM_002065.6(GLUL): c.*2644G> C single nucleotide variant Benign rs2296523 GRCh37 Chromosome 1, 182350896: 182350896
12 GLUL NM_002065.6(GLUL): c.*2463C> A single nucleotide variant Uncertain significance rs886045600 GRCh38 Chromosome 1, 182381942: 182381942
13 GLUL NM_002065.6(GLUL): c.*2463C> A single nucleotide variant Uncertain significance rs886045600 GRCh37 Chromosome 1, 182351077: 182351077
14 GLUL NM_002065.6(GLUL): c.*2313C> T single nucleotide variant Uncertain significance rs886045601 GRCh38 Chromosome 1, 182382092: 182382092
15 GLUL NM_002065.6(GLUL): c.*2313C> T single nucleotide variant Uncertain significance rs886045601 GRCh37 Chromosome 1, 182351227: 182351227
16 GLUL NM_002065.6(GLUL): c.-412C> T single nucleotide variant Uncertain significance rs886045620 GRCh37 Chromosome 1, 182360856: 182360856
17 GLUL NM_002065.6(GLUL): c.-412C> T single nucleotide variant Uncertain significance rs886045620 GRCh38 Chromosome 1, 182391721: 182391721
18 GLUL NM_002065.6(GLUL): c.*2307C> T single nucleotide variant Benign rs2296521 GRCh38 Chromosome 1, 182382098: 182382098
19 GLUL NM_002065.6(GLUL): c.*2307C> T single nucleotide variant Benign rs2296521 GRCh37 Chromosome 1, 182351233: 182351233
20 GLUL NM_002065.6(GLUL): c.*2130T> A single nucleotide variant Uncertain significance rs886045602 GRCh38 Chromosome 1, 182382275: 182382275
21 GLUL NM_002065.6(GLUL): c.*2130T> A single nucleotide variant Uncertain significance rs886045602 GRCh37 Chromosome 1, 182351410: 182351410
22 GLUL NM_002065.6(GLUL): c.*2074dup duplication Uncertain significance rs111775366 GRCh38 Chromosome 1, 182382331: 182382331
23 GLUL NM_002065.6(GLUL): c.*2074dup duplication Uncertain significance rs111775366 GRCh37 Chromosome 1, 182351466: 182351466
24 GLUL NM_002065.6(GLUL): c.*2021G> T single nucleotide variant Likely benign rs16858921 GRCh38 Chromosome 1, 182382384: 182382384
25 GLUL NM_002065.6(GLUL): c.*2021G> T single nucleotide variant Likely benign rs16858921 GRCh37 Chromosome 1, 182351519: 182351519
26 GLUL NM_002065.6(GLUL): c.*1958G> A single nucleotide variant Uncertain significance rs79056692 GRCh38 Chromosome 1, 182382447: 182382447
27 GLUL NM_002065.6(GLUL): c.*1958G> A single nucleotide variant Uncertain significance rs79056692 GRCh37 Chromosome 1, 182351582: 182351582
28 GLUL NM_002065.6(GLUL): c.*1913A> T single nucleotide variant Benign rs4517308 GRCh38 Chromosome 1, 182382492: 182382492
29 GLUL NM_002065.6(GLUL): c.*1913A> T single nucleotide variant Benign rs4517308 GRCh37 Chromosome 1, 182351627: 182351627
30 GLUL NM_002065.6(GLUL): c.*1910_*1913delAAGAinsTCATTTAAGT indel Uncertain significance rs886045605 GRCh38 Chromosome 1, 182382492: 182382495
31 GLUL NM_002065.6(GLUL): c.*1910_*1913delAAGAinsTCATTTAAGT indel Uncertain significance rs886045605 GRCh37 Chromosome 1, 182351627: 182351630
32 GLUL NM_002065.6(GLUL): c.*1790C> T single nucleotide variant Uncertain significance rs886045606 GRCh38 Chromosome 1, 182382615: 182382615
33 GLUL NM_002065.6(GLUL): c.*1790C> T single nucleotide variant Uncertain significance rs886045606 GRCh37 Chromosome 1, 182351750: 182351750
34 GLUL NM_002065.6(GLUL): c.*1596G> A single nucleotide variant Uncertain significance rs779753907 GRCh38 Chromosome 1, 182382809: 182382809
35 GLUL NM_002065.6(GLUL): c.*1596G> A single nucleotide variant Uncertain significance rs779753907 GRCh37 Chromosome 1, 182351944: 182351944
36 GLUL NM_002065.6(GLUL): c.*1469_*1470del deletion Likely benign rs138636848 GRCh38 Chromosome 1, 182382935: 182382936
37 GLUL NM_002065.6(GLUL): c.*1469_*1470del deletion Likely benign rs138636848 GRCh37 Chromosome 1, 182352070: 182352071
38 GLUL NM_002065.6(GLUL): c.*1276C> T single nucleotide variant Uncertain significance rs143904819 GRCh37 Chromosome 1, 182352264: 182352264
39 GLUL NM_002065.6(GLUL): c.*1276C> T single nucleotide variant Uncertain significance rs143904819 GRCh38 Chromosome 1, 182383129: 182383129
40 GLUL NM_002065.6(GLUL): c.*1218G> A single nucleotide variant Uncertain significance rs549506269 GRCh37 Chromosome 1, 182352322: 182352322
41 GLUL NM_002065.6(GLUL): c.*1218G> A single nucleotide variant Uncertain significance rs549506269 GRCh38 Chromosome 1, 182383187: 182383187
42 GLUL NM_002065.6(GLUL): c.*981T> G single nucleotide variant Uncertain significance rs886045609 GRCh37 Chromosome 1, 182352559: 182352559
43 GLUL NM_002065.6(GLUL): c.*981T> G single nucleotide variant Uncertain significance rs886045609 GRCh38 Chromosome 1, 182383424: 182383424
44 GLUL NM_002065.6(GLUL): c.*922A> G single nucleotide variant Likely benign rs8762 GRCh37 Chromosome 1, 182352618: 182352618
45 GLUL NM_002065.6(GLUL): c.*922A> G single nucleotide variant Likely benign rs8762 GRCh38 Chromosome 1, 182383483: 182383483
46 GLUL NM_002065.6(GLUL): c.*919A> G single nucleotide variant Benign rs7734 GRCh37 Chromosome 1, 182352621: 182352621
47 GLUL NM_002065.6(GLUL): c.*919A> G single nucleotide variant Benign rs7734 GRCh38 Chromosome 1, 182383486: 182383486
48 GLUL NM_002065.6(GLUL): c.*850T> C single nucleotide variant Uncertain significance rs886045610 GRCh37 Chromosome 1, 182352690: 182352690
49 GLUL NM_002065.6(GLUL): c.*850T> C single nucleotide variant Uncertain significance rs886045610 GRCh38 Chromosome 1, 182383555: 182383555
50 GLUL NM_002065.6(GLUL): c.930C> T (p.Asn310=) single nucleotide variant Uncertain significance rs369280031 GRCh38 Chromosome 1, 182384597: 182384597

Expression for Glutamine Deficiency, Congenital

Search GEO for disease gene expression data for Glutamine Deficiency, Congenital.

Pathways for Glutamine Deficiency, Congenital

Pathways related to Glutamine Deficiency, Congenital according to KEGG:

38
# Name Kegg Source Accession
1 Alanine, aspartate and glutamate metabolism hsa00250
2 Arginine biosynthesis hsa00220
3 Nitrogen metabolism hsa00910
4 Glutamatergic synapse hsa04724
5 GABAergic synapse hsa04727

GO Terms for Glutamine Deficiency, Congenital

Sources for Glutamine Deficiency, Congenital

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 EFO
18 ExPASy
20 FMA
29 GO
30 GTR
31 HGMD
32 HMDB
33 HPO
34 ICD10
35 ICD10 via Orphanet
36 ICD9CM
37 IUPHAR
38 KEGG
39 LifeMap
41 LOVD
43 MedGen
45 MeSH
46 MESH via Orphanet
47 MGI
50 NCI
51 NCIt
52 NDF-RT
55 NINDS
56 Novoseek
58 OMIM
59 OMIM via Orphanet
63 PubMed
65 QIAGEN
70 SNOMED-CT via HPO
71 SNOMED-CT via Orphanet
72 TGDB
73 Tocris
74 UMLS
75 UMLS via Orphanet
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