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 57 53 74 29 13 6 40 72
Glutamine Synthase Deficiency, Congenital Systemic 57 74
Congenital Systemic Glutamine Deficiency 74 37
Congenital Brain Dysgenesis Due to Glutamine Synthetase Deficiency 59
Glutamine Synthetase Deficiency, Congenital Systemic 53
Inherited Glutamine Synthetase Deficiency 59
Congenital Glutamine Deficiency 53
Inherited Gs Deficiency 59
Csgd 74

Characteristics:

Orphanet epidemiological data:

59
congenital brain dysgenesis due to glutamine synthetase deficiency
Inheritance: Autosomal recessive; Prevalence: <1/1000000 (Worldwide); Age of onset: Infancy,Neonatal;

OMIM:

57
Inheritance:
autosomal recessive

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


HPO:

32
glutamine deficiency, congenital:
Clinical modifier death in infancy
Inheritance autosomal recessive inheritance


Classifications:



External Ids:

OMIM 57 610015
KEGG 37 H00923
MeSH 44 D000592
ICD10 via Orphanet 34 E72.8
Orphanet 59 ORPHA71278
MedGen 42 C1864910
UMLS 72 C1864910

Summaries for Glutamine Deficiency, Congenital

KEGG : 37
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, skin and cerebellum, and related phenotypes are flexion contracture and micromelia

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)

UniProtKB/Swiss-Prot : 74 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:

32 (show all 21)
# Description HPO Frequency HPO Source Accession
1 flexion contracture 32 occasional (7.5%) HP:0001371
2 micromelia 32 occasional (7.5%) HP:0002983
3 low-set ears 32 HP:0000369
4 brain atrophy 32 HP:0012444
5 seizures 32 HP:0001250
6 hyperreflexia 32 HP:0001347
7 respiratory insufficiency 32 HP:0002093
8 depressed nasal bridge 32 HP:0005280
9 wide nasal bridge 32 HP:0000431
10 generalized hypotonia 32 HP:0001290
11 skin rash 32 HP:0000988
12 severe global developmental delay 32 HP:0011344
13 apnea 32 HP:0002104
14 ventriculomegaly 32 HP:0002119
15 hyperammonemia 32 HP:0001987
16 encephalopathy 32 HP:0001298
17 hypoplasia of the corpus callosum 32 HP:0002079
18 cns hypomyelination 32 HP:0003429
19 bradycardia 32 HP:0001662
20 subependymal cysts 32 HP:0002416
21 periventricular cysts 32 HP:0007109

Symptoms via clinical synopsis from OMIM:

57
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:

41
Brain, Skin, 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. 8 71
21353613 2011
2
Congenital glutamine deficiency with glutamine synthetase mutations. 8 71
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. 38
22830360 2012

Variations for Glutamine Deficiency, Congenital

ClinVar genetic disease variations for Glutamine Deficiency, Congenital:

6 (show top 50) (show all 96)
# Gene Variation Type Significance SNP ID GRCh37 Pos GRCh38 Pos
1 GLUL NM_002065.6(GLUL): c.970C> T (p.Arg324Cys) single nucleotide variant Pathogenic rs80358214 1:182353692-182353692 1:182384557-182384557
2 GLUL NM_002065.6(GLUL): c.1021C> T (p.Arg341Cys) single nucleotide variant Pathogenic rs80358215 1:182353641-182353641 1:182384506-182384506
3 GLUL NM_002065.6(GLUL): c.970C> A (p.Arg324Ser) single nucleotide variant Pathogenic rs80358214 1:182353692-182353692 1:182384557-182384557
4 GLUL NM_002065.6(GLUL): c.603+5G> A single nucleotide variant Conflicting interpretations of pathogenicity rs140378060 1:182354890-182354890 1:182385755-182385755
5 GLUL NM_002065.6(GLUL): c.355C> T (p.Arg119Trp) single nucleotide variant Uncertain significance rs771501078 1:182355511-182355511 1:182386376-182386376
6 GLUL NM_002065.6(GLUL): c.238G> A (p.Val80Met) single nucleotide variant Uncertain significance rs151138433 1:182356356-182356356 1:182387221-182387221
7 GLUL NM_002065.6(GLUL): c.-188C> G single nucleotide variant Uncertain significance rs145293725 1:182359806-182359806 1:182390671-182390671
8 GLUL NM_002065.6(GLUL): c.-199A> G single nucleotide variant Uncertain significance rs187277313 1:182359817-182359817 1:182390682-182390682
9 GLUL NM_002065.6(GLUL): c.-745C> T single nucleotide variant Uncertain significance rs886045623 1:182361189-182361189 1:182392054-182392054
10 GLUL NM_002065.6(GLUL): c.*2604C> A single nucleotide variant Uncertain significance rs886045599 1:182350936-182350936 1:182381801-182381801
11 GLUL NM_002065.6(GLUL): c.*305C> T single nucleotide variant Uncertain significance rs886045614 1:182353235-182353235 1:182384100-182384100
12 GLUL NM_002065.6(GLUL): c.*248dup duplication Uncertain significance rs541187376 1:182353292-182353292 1:182384157-182384157
13 GLUL NM_002065.6(GLUL): c.863A> G (p.Tyr288Cys) single nucleotide variant Uncertain significance rs886045617 1:182353799-182353799 1:182384664-182384664
14 GLUL NM_002065.6(GLUL): c.997_999AAG[1] (p.Lys334del) short repeat Uncertain significance 1:182353660-182353662 1:182384525-182384527
15 GLUL NM_002065.6(GLUL): c.*2463C> A single nucleotide variant Uncertain significance rs886045600 1:182351077-182351077 1:182381942-182381942
16 GLUL NM_002065.6(GLUL): c.*2313C> T single nucleotide variant Uncertain significance rs886045601 1:182351227-182351227 1:182382092-182382092
17 GLUL NM_002065.6(GLUL): c.-412C> T single nucleotide variant Uncertain significance rs886045620 1:182360856-182360856 1:182391721-182391721
18 GLUL NM_002065.6(GLUL): c.*2130T> A single nucleotide variant Uncertain significance rs886045602 1:182351410-182351410 1:182382275-182382275
19 GLUL NM_002065.6(GLUL): c.*2074dup duplication Uncertain significance rs111775366 1:182351466-182351466 1:182382331-182382331
20 GLUL NM_002065.6(GLUL): c.*1958G> A single nucleotide variant Uncertain significance rs79056692 1:182351582-182351582 1:182382447-182382447
21 GLUL NM_002065.6(GLUL): c.*1910_*1913delinsTCATTTAAGT indel Uncertain significance rs886045605 1:182351627-182351630 1:182382492-182382495
22 GLUL NM_002065.6(GLUL): c.*1790C> T single nucleotide variant Uncertain significance rs886045606 1:182351750-182351750 1:182382615-182382615
23 GLUL NM_002065.6(GLUL): c.*1596G> A single nucleotide variant Uncertain significance rs779753907 1:182351944-182351944 1:182382809-182382809
24 GLUL NM_002065.6(GLUL): c.*1276C> T single nucleotide variant Uncertain significance rs143904819 1:182352264-182352264 1:182383129-182383129
25 GLUL NM_002065.6(GLUL): c.*1218G> A single nucleotide variant Uncertain significance rs549506269 1:182352322-182352322 1:182383187-182383187
26 GLUL NM_002065.6(GLUL): c.*981T> G single nucleotide variant Uncertain significance rs886045609 1:182352559-182352559 1:182383424-182383424
27 GLUL NM_002065.6(GLUL): c.*850T> C single nucleotide variant Uncertain significance rs886045610 1:182352690-182352690 1:182383555-182383555
28 GLUL NM_002065.6(GLUL): c.930C> T (p.Asn310=) single nucleotide variant Uncertain significance rs369280031 1:182353732-182353732 1:182384597-182384597
29 GLUL NM_002065.6(GLUL): c.-280C> T single nucleotide variant Uncertain significance rs886045618 1:182359898-182359898 1:182390763-182390763
30 GLUL NM_002065.6(GLUL): c.*2631G> C single nucleotide variant Uncertain significance rs2296522 1:182350909-182350909 1:182381774-182381774
31 GLUL NM_002065.6(GLUL): c.*2516A> G single nucleotide variant Uncertain significance rs140277335 1:182351024-182351024 1:182381889-182381889
32 GLUL NM_002065.6(GLUL): c.*2074G> A single nucleotide variant Uncertain significance rs185466076 1:182351466-182351466 1:182382331-182382331
33 GLUL NM_002065.6(GLUL): c.*687A> G single nucleotide variant Uncertain significance rs546951174 1:182352853-182352853 1:182383718-182383718
34 GLUL NM_002065.6(GLUL): c.*1919A> G single nucleotide variant Uncertain significance rs886045604 1:182351621-182351621 1:182382486-182382486
35 GLUL NM_002065.6(GLUL): c.*1772C> G single nucleotide variant Uncertain significance rs148906736 1:182351768-182351768 1:182382633-182382633
36 GLUL NM_002065.6(GLUL): c.*1357T> G single nucleotide variant Uncertain significance rs180970725 1:182352183-182352183 1:182383048-182383048
37 GLUL NM_002065.6(GLUL): c.*169G> A single nucleotide variant Uncertain significance rs886045615 1:182353371-182353371 1:182384236-182384236
38 GLUL NM_002065.6(GLUL): c.*101dup duplication Uncertain significance rs202163570 1:182353439-182353439 1:182384304-182384304
39 GLUL NM_002065.6(GLUL): c.880C> T (p.Leu294=) single nucleotide variant Uncertain significance rs199824213 1:182353782-182353782 1:182384647-182384647
40 GLUL NM_002065.6(GLUL): c.-158C> T single nucleotide variant Uncertain significance rs532574396 1:182359776-182359776 1:182390641-182390641
41 GLUL NM_002065.6(GLUL): c.-238G> A single nucleotide variant Uncertain significance rs549137282 1:182359856-182359856 1:182390721-182390721
42 GLUL NM_002065.6(GLUL): c.-241C> T single nucleotide variant Uncertain significance rs370070318 1:182359859-182359859 1:182390724-182390724
43 GLUL NM_002065.6(GLUL): c.-370+10del deletion Uncertain significance rs886045619 1:182360804-182360804 1:182391669-182391669
44 GLUL NM_002065.6(GLUL): c.-466A> G single nucleotide variant Uncertain significance rs558342179 1:182360910-182360910 1:182391775-182391775
45 GLUL NM_002065.6(GLUL): c.-680C> A single nucleotide variant Uncertain significance rs886045622 1:182361124-182361124 1:182391989-182391989
46 GLUL NM_002065.6(GLUL): c.*1978G> A single nucleotide variant Uncertain significance rs868130362 1:182351562-182351562 1:182382427-182382427
47 GLUL NM_002065.6(GLUL): c.*1932T> G single nucleotide variant Uncertain significance rs886045603 1:182351608-182351608 1:182382473-182382473
48 GLUL NM_002065.6(GLUL): c.*1563_*1566del deletion Uncertain significance rs559713506 1:182351974-182351977 1:182382839-182382842
49 GLUL NM_002065.6(GLUL): c.*1510G> T single nucleotide variant Uncertain significance rs886045608 1:182352030-182352030 1:182382895-182382895
50 GLUL NM_002065.6(GLUL): c.*1057A> G single nucleotide variant Uncertain significance rs571517535 1:182352483-182352483 1:182383348-182383348

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

74
# 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:

37
# 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 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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