CSGD
MCID: GLT011
MIFTS: 32

Glutamine Deficiency, Congenital (CSGD)

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

Aliases & Classifications for Glutamine Deficiency, Congenital

MalaCards integrated aliases for Glutamine Deficiency, Congenital:

Name: Glutamine Deficiency, Congenital 57 20 72 13 39 70
Congenital Brain Dysgenesis Due to Glutamine Synthetase Deficiency 58 29 6
Glutamine Synthase Deficiency, Congenital Systemic 57 72
Congenital Systemic Glutamine Deficiency 72 36
Glutamine Synthetase Deficiency, Congenital Systemic 20
Inherited Glutamine Synthetase Deficiency 58
Congenital Glutamine Deficiency 20
Inherited Gs Deficiency 58
Csgd 72

Characteristics:

Orphanet epidemiological data:

58
congenital brain dysgenesis due to glutamine synthetase deficiency
Inheritance: Autosomal recessive; Prevalence: <1/1000000 (Worldwide); Age of onset: Infancy,Neonatal;

OMIM®:

57 (Updated 20-May-2021)
Inheritance:
autosomal recessive

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


HPO:

31
glutamine deficiency, congenital:
Onset and clinical course neonatal death antenatal onset
Inheritance autosomal recessive inheritance


Classifications:

Orphanet: 58  
Rare neurological diseases
Inborn errors of metabolism


Summaries for Glutamine Deficiency, Congenital

KEGG : 36 Congenital systemic glutamine deficiency (CSGD) is a rare developmental disorder with severe brain malformation resulting in multi-organ failure and neonatal death. Glutamine synthetase plays a major role in ammonia detoxification, interorgan nitrogen flux, acid-base homeostasis, and cell signaling. It has been reported that glutamine was largely absent from affected patients serum, urine, and cerebrospinal fluid.

MalaCards based summary : Glutamine Deficiency, Congenital, also known as congenital brain dysgenesis due to glutamine synthetase deficiency, is related to mast cell activation syndrome and helix 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 and cerebellum, and related phenotypes are depressed nasal bridge and recurrent respiratory infections

OMIM® : 57 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) (Updated 20-May-2021)

UniProtKB/Swiss-Prot : 72 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
2 helix syndrome 10.1
3 encephalopathy 10.0
4 paroxysmal extreme pain disorder 9.9
5 gastroenteritis 9.9

Graphical network of the top 20 diseases related to Glutamine Deficiency, Congenital:



Diseases related to Glutamine Deficiency, Congenital

Symptoms & Phenotypes for Glutamine Deficiency, Congenital

Human phenotypes related to Glutamine Deficiency, Congenital:

31 (show all 26)
# Description HPO Frequency HPO Source Accession
1 depressed nasal bridge 31 very rare (1%) HP:0005280
2 recurrent respiratory infections 31 very rare (1%) HP:0002205
3 wide nasal bridge 31 very rare (1%) HP:0000431
4 short nose 31 very rare (1%) HP:0003196
5 anteverted nares 31 very rare (1%) HP:0000463
6 low-set ears 31 very rare (1%) HP:0000369
7 neonatal respiratory distress 31 very rare (1%) HP:0002643
8 apnea 31 very rare (1%) HP:0002104
9 erythema 31 very rare (1%) HP:0010783
10 hyperammonemia 31 very rare (1%) HP:0001987
11 micromelia 31 very rare (1%) HP:0002983
12 severe global developmental delay 31 very rare (1%) HP:0011344
13 thin vermilion border 31 very rare (1%) HP:0000233
14 hypoplasia of the corpus callosum 31 very rare (1%) HP:0002079
15 generalized hypotonia 31 very rare (1%) HP:0001290
16 camptodactyly 31 very rare (1%) HP:0012385
17 brain atrophy 31 very rare (1%) HP:0012444
18 bradycardia 31 very rare (1%) HP:0001662
19 lower limb hyperreflexia 31 very rare (1%) HP:0002395
20 dilation of lateral ventricles 31 very rare (1%) HP:0006956
21 subependymal cysts 31 very rare (1%) HP:0002416
22 hypoglutaminemia 31 very rare (1%) HP:0500147
23 decreased csf glutamine concentration 31 very rare (1%) HP:0500198
24 seizure 31 very rare (1%) HP:0001250
25 encephalopathy 31 HP:0001298
26 cns hypomyelination 31 HP:0003429

Symptoms via clinical synopsis from OMIM®:

57 (Updated 20-May-2021)
Neurologic Central Nervous System:
seizures
hyperreflexia
ventriculomegaly
encephalopathy
brain atrophy
more
Head And Neck Ears:
low-set ears

Cardiovascular Heart:
bradycardia

Skeletal:
contractures (1 patient)

Skin Nails Hair Skin:
blistering erythematous rash

Respiratory:
respiratory insufficiency
apnea

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 (Updated 20-May-2021)

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 Congenital Brain Dysgenesis Due to Glutamine Synthetase Deficiency 29 GLUL

Anatomical Context for Glutamine Deficiency, Congenital

MalaCards organs/tissues related to Glutamine Deficiency, Congenital:

40
Brain, Cerebellum

Publications for Glutamine Deficiency, Congenital

Articles related to Glutamine Deficiency, Congenital:

# Title Authors PMID Year
1
Natural course of glutamine synthetase deficiency in a 3 year old patient. 6 57
21353613 2011
2
Congenital glutamine deficiency with glutamine synthetase mutations. 6 57
16267323 2005
3
Glutamine supplementation in a child with inherited GS deficiency improves the clinical status and partially corrects the peripheral and central amino acid imbalance. 61
22830360 2012

Variations for Glutamine Deficiency, Congenital

ClinVar genetic disease variations for Glutamine Deficiency, Congenital:

6 (show top 50) (show all 142)
# Gene Name Type Significance ClinVarId dbSNP ID Position
1 GLUL NM_001033044.4(GLUL):c.970C>T (p.Arg324Cys) SNV Pathogenic 16083 rs80358214 GRCh37: 1:182353692-182353692
GRCh38: 1:182384557-182384557
2 GLUL NM_001033044.4(GLUL):c.1021C>T (p.Arg341Cys) SNV Pathogenic 16084 rs80358215 GRCh37: 1:182353641-182353641
GRCh38: 1:182384506-182384506
3 GLUL NM_001033044.4(GLUL):c.970C>A (p.Arg324Ser) SNV Pathogenic 29734 rs80358214 GRCh37: 1:182353692-182353692
GRCh38: 1:182384557-182384557
4 GLUL NM_001033044.4(GLUL):c.415del (p.Leu139fs) Deletion Pathogenic 1048524 GRCh37: 1:182355451-182355451
GRCh38: 1:182386316-182386316
5 GLUL NM_001033044.4(GLUL):c.1075T>G (p.Cys359Gly) SNV Likely pathogenic 1048523 GRCh37: 1:182353587-182353587
GRCh38: 1:182384452-182384452
6 GLUL NM_001033044.4(GLUL):c.880C>T (p.Leu294=) SNV Conflicting interpretations of pathogenicity 293942 rs199824213 GRCh37: 1:182353782-182353782
GRCh38: 1:182384647-182384647
7 GLUL NM_001033044.4(GLUL):c.238G>A (p.Val80Met) SNV Uncertain significance 293948 rs151138433 GRCh37: 1:182356356-182356356
GRCh38: 1:182387221-182387221
8 GLUL NM_001033044.4(GLUL):c.*2604C>A SNV Uncertain significance 293885 rs886045599 GRCh37: 1:182350936-182350936
GRCh38: 1:182381801-182381801
9 GLUL NM_001033044.4(GLUL):c.*2463C>A SNV Uncertain significance 293888 rs886045600 GRCh37: 1:182351077-182351077
GRCh38: 1:182381942-182381942
10 GLUL NM_001033044.4(GLUL):c.-14+1038C>T SNV Uncertain significance 293951 rs532574396 GRCh37: 1:182359776-182359776
GRCh38: 1:182390641-182390641
11 GLUL NM_001033044.4(GLUL):c.*399C>T SNV Uncertain significance 293933 rs886045613 GRCh37: 1:182353141-182353141
GRCh38: 1:182384006-182384006
12 GLUL NM_001033044.4(GLUL):c.*1286_*1288ATT[1] Microsatellite Uncertain significance 293916 rs769384071 GRCh37: 1:182352249-182352251
GRCh38: 1:182383114-182383116
13 GLUL NM_001033044.4(GLUL):c.*1772C>G SNV Uncertain significance 293905 rs148906736 GRCh37: 1:182351768-182351768
GRCh38: 1:182382633-182382633
14 GLUL NM_002065.6(GLUL):c.-674_-673CT[1] Microsatellite Uncertain significance 293968 rs886045621 GRCh37: 1:182361115-182361116
GRCh38: 1:182391980-182391981
15 GLUL NM_001033044.4(GLUL):c.*981T>G SNV Uncertain significance 293922 rs886045609 GRCh37: 1:182352559-182352559
GRCh38: 1:182383424-182383424
16 GLUL NM_001033044.4(GLUL):c.*1932T>G SNV Uncertain significance 293899 rs886045603 GRCh37: 1:182351608-182351608
GRCh38: 1:182382473-182382473
17 GLUL NM_001033044.4(GLUL):c.-14+958G>A SNV Uncertain significance 293954 rs549137282 GRCh37: 1:182359856-182359856
GRCh38: 1:182390721-182390721
18 GLUL NM_001033044.4(GLUL):c.*1596G>A SNV Uncertain significance 293908 rs779753907 GRCh37: 1:182351944-182351944
GRCh38: 1:182382809-182382809
19 GLUL NM_001033044.4(GLUL):c.*687A>G SNV Uncertain significance 293928 rs546951174 GRCh37: 1:182352853-182352853
GRCh38: 1:182383718-182383718
20 GLUL NM_001033044.4(GLUL):c.*1510G>T SNV Uncertain significance 293911 rs886045608 GRCh37: 1:182352030-182352030
GRCh38: 1:182382895-182382895
21 GLUL NM_001033044.4(GLUL):c.*481G>A SNV Uncertain significance 293931 rs886045612 GRCh37: 1:182353059-182353059
GRCh38: 1:182383924-182383924
22 GLUL NM_001033044.4(GLUL):c.*248dup Duplication Uncertain significance 293937 rs541187376 GRCh37: 1:182353291-182353292
GRCh38: 1:182384156-182384157
23 GLUL NM_001033044.4(GLUL):c.*1057A>G SNV Uncertain significance 293920 rs571517535 GRCh37: 1:182352483-182352483
GRCh38: 1:182383348-182383348
24 GLUL NM_001033044.4(GLUL):c.*101dup Duplication Uncertain significance 293940 rs202163570 GRCh37: 1:182353438-182353439
GRCh38: 1:182384303-182384304
25 GLUL NM_001033044.4(GLUL):c.-14+916C>T SNV Uncertain significance 293957 rs886045618 GRCh37: 1:182359898-182359898
GRCh38: 1:182390763-182390763
26 GLUL NM_001033044.4(GLUL):c.*2074dup Duplication Uncertain significance 293894 rs111775366 GRCh37: 1:182351465-182351466
GRCh38: 1:182382330-182382331
27 GLUL NM_001033044.4(GLUL):c.-56C>T SNV Uncertain significance 293963 rs886045620 GRCh37: 1:182360856-182360856
GRCh38: 1:182391721-182391721
28 GLUL NM_001033044.4(GLUL):c.*1919A>G SNV Uncertain significance 293900 rs886045604 GRCh37: 1:182351621-182351621
GRCh38: 1:182382486-182382486
29 GLUL NM_001033044.4(GLUL):c.355C>T (p.Arg119Trp) SNV Uncertain significance 293946 rs771501078 GRCh37: 1:182355511-182355511
GRCh38: 1:182386376-182386376
30 GLUL NM_001033044.4(GLUL):c.863A>G (p.Tyr288Cys) SNV Uncertain significance 293943 rs886045617 GRCh37: 1:182353799-182353799
GRCh38: 1:182384664-182384664
31 GLUL NM_001033044.4(GLUL):c.*1978G>A SNV Uncertain significance 293897 rs868130362 GRCh37: 1:182351562-182351562
GRCh38: 1:182382427-182382427
32 GLUL NM_001033044.4(GLUL):c.*850T>C SNV Uncertain significance 293926 rs886045610 GRCh37: 1:182352690-182352690
GRCh38: 1:182383555-182383555
33 GLUL NM_001033044.4(GLUL):c.*2631G>C SNV Uncertain significance 293883 rs2296522 GRCh37: 1:182350909-182350909
GRCh38: 1:182381774-182381774
34 GLUL NM_001033044.4(GLUL):c.-14+1008C>G SNV Uncertain significance 293952 rs145293725 GRCh37: 1:182359806-182359806
GRCh38: 1:182390671-182390671
35 GLUL NM_001033044.4(GLUL):c.*305C>T SNV Uncertain significance 293935 rs886045614 GRCh37: 1:182353235-182353235
GRCh38: 1:182384100-182384100
36 GLUL NM_001033044.4(GLUL):c.*2365G>A SNV Uncertain significance 293889 rs140748780 GRCh37: 1:182351175-182351175
GRCh38: 1:182382040-182382040
37 GLUL NM_002065.6(GLUL):c.-745C>T SNV Uncertain significance 293972 rs886045623 GRCh37: 1:182361189-182361189
GRCh38: 1:182392054-182392054
38 GLUL NM_001033044.4(GLUL):c.-14+955C>T SNV Uncertain significance 293955 rs370070318 GRCh37: 1:182359859-182359859
GRCh38: 1:182390724-182390724
39 GLUL NM_001033044.4(GLUL):c.*2130T>A SNV Uncertain significance 293892 rs886045602 GRCh37: 1:182351410-182351410
GRCh38: 1:182382275-182382275
40 GLUL NM_001033044.4(GLUL):c.*1033G>C SNV Uncertain significance 293921 rs186333925 GRCh37: 1:182352507-182352507
GRCh38: 1:182383372-182383372
41 GLUL NM_001033044.4(GLUL):c.930C>T (p.Asn310=) SNV Uncertain significance 293941 rs369280031 GRCh37: 1:182353732-182353732
GRCh38: 1:182384597-182384597
42 GLUL NM_001033044.4(GLUL):c.*169G>A SNV Uncertain significance 293938 rs886045615 GRCh37: 1:182353371-182353371
GRCh38: 1:182384236-182384236
43 GLUL NM_001033044.4(GLUL):c.-110A>G SNV Uncertain significance 293964 rs558342179 GRCh37: 1:182360910-182360910
GRCh38: 1:182391775-182391775
44 GLUL NM_001033044.4(GLUL):c.*1218G>A SNV Uncertain significance 293918 rs549506269 GRCh37: 1:182352322-182352322
GRCh38: 1:182383187-182383187
45 GLUL NM_001033044.4(GLUL):c.*1910_*1913delinsTCATTTAAGT Indel Uncertain significance 293901 rs886045605 GRCh37: 1:182351627-182351630
GRCh38: 1:182382492-182382495
46 GLUL NM_001033044.4(GLUL):c.-14+997A>G SNV Uncertain significance 293953 rs187277313 GRCh37: 1:182359817-182359817
GRCh38: 1:182390682-182390682
47 GLUL NM_001033044.4(GLUL):c.*2313C>T SNV Uncertain significance 293890 rs886045601 GRCh37: 1:182351227-182351227
GRCh38: 1:182382092-182382092
48 GLUL NM_001033044.4(GLUL):c.*1790C>T SNV Uncertain significance 293904 rs886045606 GRCh37: 1:182351750-182351750
GRCh38: 1:182382615-182382615
49 GLUL NM_002065.6(GLUL):c.-564C>A SNV Uncertain significance 293967 rs760794180 GRCh37: 1:182361008-182361008
GRCh38: 1:182391873-182391873
50 GLUL NM_001033044.4(GLUL):c.*1563_*1566del Deletion Uncertain significance 293910 rs559713506 GRCh37: 1:182351974-182351977
GRCh38: 1:182382839-182382842

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

72
# Symbol AA change Variation ID SNP ID
1 GLUL p.Arg324Cys VAR_026560 rs80358214
2 GLUL p.Arg341Cys VAR_026561 rs80358215

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:

36
# 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
19 FMA
20 GARD
28 GO
29 GTR
30 HMDB
31 HPO
32 ICD10
33 ICD10 via Orphanet
34 ICD9CM
35 IUPHAR
36 KEGG
37 LifeMap
39 LOVD
41 MedGen
44 MeSH
45 MESH via Orphanet
46 MGI
49 NCI
50 NCIt
51 NDF-RT
53 NINDS
54 Novoseek
56 OMIM via Orphanet
57 OMIM® (Updated 20-May-2021)
61 PubMed
63 QIAGEN
68 SNOMED-CT via HPO
69 Tocris
70 UMLS
71 UMLS via Orphanet
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