CSGD
MCID: GLT011
MIFTS: 31

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 56 52 73 29 13 6 39 71
Glutamine Synthase Deficiency, Congenital Systemic 56 73
Congenital Systemic Glutamine Deficiency 73 36
Congenital Brain Dysgenesis Due to Glutamine Synthetase Deficiency 58
Glutamine Synthetase Deficiency, Congenital Systemic 52
Inherited Glutamine Synthetase Deficiency 58
Congenital Glutamine Deficiency 52
Inherited Gs Deficiency 58
Csgd 73

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:

56
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:
Clinical modifier death in infancy
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 glutamine synthase deficiency, congenital systemic, 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, cerebellum and skin, and related phenotypes are flexion contracture and micromelia

OMIM : 56 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)

UniProtKB/Swiss-Prot : 73 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 10.5
2 helix syndrome 10.4
3 paroxysmal extreme pain disorder 10.2
4 encephalopathy 9.9

Symptoms & Phenotypes for Glutamine Deficiency, Congenital

Human phenotypes related to Glutamine Deficiency, Congenital:

31 (show all 21)
# Description HPO Frequency HPO Source Accession
1 flexion contracture 31 occasional (7.5%) HP:0001371
2 micromelia 31 occasional (7.5%) HP:0002983
3 low-set ears 31 HP:0000369
4 brain atrophy 31 HP:0012444
5 seizures 31 HP:0001250
6 hyperreflexia 31 HP:0001347
7 respiratory insufficiency 31 HP:0002093
8 depressed nasal bridge 31 HP:0005280
9 wide nasal bridge 31 HP:0000431
10 generalized hypotonia 31 HP:0001290
11 skin rash 31 HP:0000988
12 severe global developmental delay 31 HP:0011344
13 apnea 31 HP:0002104
14 ventriculomegaly 31 HP:0002119
15 hyperammonemia 31 HP:0001987
16 hypoplasia of the corpus callosum 31 HP:0002079
17 encephalopathy 31 HP:0001298
18 bradycardia 31 HP:0001662
19 cns hypomyelination 31 HP:0003429
20 subependymal cysts 31 HP:0002416
21 periventricular cysts 31 HP:0007109

Symptoms via clinical synopsis from OMIM:

56
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 29 GLUL

Anatomical Context for Glutamine Deficiency, Congenital

MalaCards organs/tissues related to Glutamine Deficiency, Congenital:

40
Brain, Cerebellum, Skin

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. 56 6
21353613 2011
2
Congenital glutamine deficiency with glutamine synthetase mutations. 56 6
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 96) ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎
# Gene Name Type Significance ClinVarId dbSNP ID GRCh37 Pos GRCh38 Pos
1 GLUL NM_001033044.4(GLUL):c.970C>T (p.Arg324Cys)SNV Pathogenic 16083 rs80358214 1:182353692-182353692 1:182384557-182384557
2 GLUL NM_001033044.4(GLUL):c.1021C>T (p.Arg341Cys)SNV Pathogenic 16084 rs80358215 1:182353641-182353641 1:182384506-182384506
3 GLUL NM_001033044.4(GLUL):c.970C>A (p.Arg324Ser)SNV Pathogenic 29734 rs80358214 1:182353692-182353692 1:182384557-182384557
4 GLUL NM_001033044.4(GLUL):c.880C>T (p.Leu294=)SNV Conflicting interpretations of pathogenicity 293942 rs199824213 1:182353782-182353782 1:182384647-182384647
5 GLUL NM_001033044.4(GLUL):c.603+5G>ASNV Conflicting interpretations of pathogenicity 293945 rs140378060 1:182354890-182354890 1:182385755-182385755
6 GLUL NM_001033044.4(GLUL):c.355C>T (p.Arg119Trp)SNV Uncertain significance 293946 rs771501078 1:182355511-182355511 1:182386376-182386376
7 GLUL NM_001033044.4(GLUL):c.238G>A (p.Val80Met)SNV Uncertain significance 293948 rs151138433 1:182356356-182356356 1:182387221-182387221
8 GLUL NM_001033044.4(GLUL):c.-14+1008C>GSNV Uncertain significance 293952 rs145293725 1:182359806-182359806 1:182390671-182390671
9 GLUL NM_001033044.4(GLUL):c.-14+997A>GSNV Uncertain significance 293953 rs187277313 1:182359817-182359817 1:182390682-182390682
10 GLUL NM_001033044.4(GLUL):c.*492_*493GA[2]short repeat Uncertain significance 293930 rs774211990 1:182353043-182353044 1:182383908-182383909
11 GLUL NM_001033044.4(GLUL):c.*481G>ASNV Uncertain significance 293931 rs886045612 1:182353059-182353059 1:182383924-182383924
12 GLUL NM_001033044.4(GLUL):c.*305C>TSNV Uncertain significance 293935 rs886045614 1:182353235-182353235 1:182384100-182384100
13 GLUL NM_001033044.4(GLUL):c.*248dupduplication Uncertain significance 293937 rs541187376 1:182353291-182353292 1:182384156-182384157
14 GLUL NM_001033044.4(GLUL):c.863A>G (p.Tyr288Cys)SNV Uncertain significance 293943 rs886045617 1:182353799-182353799 1:182384664-182384664
15 GLUL NM_001033044.4(GLUL):c.997_999AAG[1] (p.Lys334del)short repeat Uncertain significance 587629 rs1558157160 1:182353660-182353662 1:182384525-182384527
16 GLUL NM_001033044.4(GLUL):c.-14+1038C>TSNV Uncertain significance 293951 rs532574396 1:182359776-182359776 1:182390641-182390641
17 GLUL NM_001033044.4(GLUL):c.-14+958G>ASNV Uncertain significance 293954 rs549137282 1:182359856-182359856 1:182390721-182390721
18 GLUL NM_001033044.4(GLUL):c.-14+955C>TSNV Uncertain significance 293955 rs370070318 1:182359859-182359859 1:182390724-182390724
19 GLUL NM_001033044.4(GLUL):c.-14+10deldeletion Uncertain significance 293961 rs886045619 1:182360804-182360804 1:182391669-182391669
20 GLUL NM_001033044.4(GLUL):c.-110A>GSNV Uncertain significance 293964 rs558342179 1:182360910-182360910 1:182391775-182391775
21 GLUL NM_002065.6(GLUL):c.-680C>ASNV Uncertain significance 293969 rs886045622 1:182361124-182361124 1:182391989-182391989
22 GLUL NM_001033044.4(GLUL):c.*1978G>ASNV Uncertain significance 293897 rs868130362 1:182351562-182351562 1:182382427-182382427
23 GLUL NM_001033044.4(GLUL):c.*1932T>GSNV Uncertain significance 293899 rs886045603 1:182351608-182351608 1:182382473-182382473
24 GLUL NM_001033044.4(GLUL):c.*1563_*1566deldeletion Uncertain significance 293910 rs559713506 1:182351974-182351977 1:182382839-182382842
25 GLUL NM_001033044.4(GLUL):c.*1510G>TSNV Uncertain significance 293911 rs886045608 1:182352030-182352030 1:182382895-182382895
26 GLUL NM_001033044.4(GLUL):c.*1057A>GSNV Uncertain significance 293920 rs571517535 1:182352483-182352483 1:182383348-182383348
27 GLUL NM_001033044.4(GLUL):c.*1033G>CSNV Uncertain significance 293921 rs186333925 1:182352507-182352507 1:182383372-182383372
28 GLUL NM_001033044.4(GLUL):c.*717T>CSNV Uncertain significance 293927 rs886045611 1:182352823-182352823 1:182383688-182383688
29 GLUL NM_001033044.4(GLUL):c.*399C>TSNV Uncertain significance 293933 rs886045613 1:182353141-182353141 1:182384006-182384006
30 GLUL NM_001033044.4(GLUL):c.*272C>GSNV Uncertain significance 293936 rs184789378 1:182353268-182353268 1:182384133-182384133
31 GLUL NM_001033044.4(GLUL):c.*129G>TSNV Uncertain significance 293939 rs886045616 1:182353411-182353411 1:182384276-182384276
32 GLUL NM_001033044.4(GLUL):c.268C>T (p.Arg90Cys)SNV Uncertain significance 293947 rs199746338 1:182356326-182356326 1:182387191-182387191
33 GLUL NM_001033044.4(GLUL):c.-14+934C>GSNV Uncertain significance 293956 rs534569561 1:182359880-182359880 1:182390745-182390745
34 GLUL NM_001033044.4(GLUL):c.-14+905T>CSNV Uncertain significance 293958 rs78752021 1:182359909-182359909 1:182390774-182390774
35 GLUL NM_002065.6(GLUL):c.-564C>ASNV Uncertain significance 293967 rs760794180 1:182361008-182361008 1:182391873-182391873
36 GLUL NM_002065.6(GLUL):c.-674_-673CT[1]short repeat Uncertain significance 293968 rs886045621 1:182361115-182361116 1:182391980-182391981
37 GLUL NM_001033044.4(GLUL):c.*2494G>TSNV Uncertain significance 293887 rs77070600 1:182351046-182351046 1:182381911-182381911
38 GLUL NM_001033044.4(GLUL):c.*2365G>ASNV Uncertain significance 293889 rs140748780 1:182351175-182351175 1:182382040-182382040
39 GLUL NM_001033044.4(GLUL):c.*1762A>GSNV Uncertain significance 293906 rs138138013 1:182351778-182351778 1:182382643-182382643
40 GLUL NM_001033044.4(GLUL):c.*1692A>GSNV Uncertain significance 293907 rs886045607 1:182351848-182351848 1:182382713-182382713
41 GLUL NM_001033044.4(GLUL):c.*1594_*1595deldeletion Uncertain significance 293909 rs367629181 1:182351945-182351946 1:182382810-182382811
42 GLUL NM_002065.6(GLUL):c.-745C>TSNV Uncertain significance 293972 rs886045623 1:182361189-182361189 1:182392054-182392054
43 GLUL NM_001033044.4(GLUL):c.*2604C>ASNV Uncertain significance 293885 rs886045599 1:182350936-182350936 1:182381801-182381801
44 GLUL NM_001033044.4(GLUL):c.*1286_*1288ATT[1]short repeat Uncertain significance 293916 rs769384071 1:182352249-182352251 1:182383114-182383116
45 GLUL NM_001033044.4(GLUL):c.*1058G>ASNV Uncertain significance 293919 rs146631739 1:182352482-182352482 1:182383347-182383347
46 GLUL NM_001033044.4(GLUL):c.*966A>GSNV Uncertain significance 293923 rs7543200 1:182352574-182352574 1:182383439-182383439
47 GLUL NM_001033044.4(GLUL):c.*2463C>ASNV Uncertain significance 293888 rs886045600 1:182351077-182351077 1:182381942-182381942
48 GLUL NM_001033044.4(GLUL):c.*2313C>TSNV Uncertain significance 293890 rs886045601 1:182351227-182351227 1:182382092-182382092
49 GLUL NM_001033044.4(GLUL):c.*2130T>ASNV Uncertain significance 293892 rs886045602 1:182351410-182351410 1:182382275-182382275
50 GLUL NM_001033044.4(GLUL):c.*2074dupduplication Uncertain significance 293894 rs111775366 1:182351465-182351466 1:182382330-182382331

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

73
# 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
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
43 MeSH
44 MESH via Orphanet
45 MGI
48 NCI
49 NCIt
50 NDF-RT
53 NINDS
54 Novoseek
56 OMIM
57 OMIM via Orphanet
61 PubMed
63 QIAGEN
68 SNOMED-CT via HPO
69 TGDB
70 Tocris
71 UMLS
72 UMLS via Orphanet
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