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MCID: NCT003
MIFTS: 36

N-Acetylglutamate Synthase Deficiency

Categories: Genetic diseases, Rare diseases, Metabolic diseases
Genes Variations Related diseases Publications Pathways Symptoms & Phenotypes Drugs
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Aliases & Classifications for N-Acetylglutamate Synthase Deficiency

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MalaCards integrated aliases for N-Acetylglutamate Synthase Deficiency:

Name: N-Acetylglutamate Synthase Deficiency 57 76 53 25 75 13
Nags Deficiency 57 53 25 59 75 55
Hyperammonemia, Type Iii 25 29 6 73
Hyperammonemia Due to N-Acetylglutamate Synthetase Deficiency 57 53 75
N-Acetylglutamate Synthetase Deficiency 57 25 75
Nagsd 57 75
Hyperammonemia Due to N-Acetylglutamate Synthase Deficiency 59
N-Acetyl Glutamate Synthetase Deficiency 53
N-Acetylglutamate Synthase Deficiency 37
Deficiency, N-Acetylglutamate Synthase 40
N-Acetylglutamate Synthase 13
Nag Synthetase Deficiency 53

Characteristics:

Orphanet epidemiological data:

59
hyperammonemia due to n-acetylglutamate synthase deficiency
Inheritance: Autosomal recessive; Age of onset: All ages; Age of death: any age;

OMIM:

57
Inheritance:
autosomal recessive

Miscellaneous:
variable phenotype depending on residual enzyme activity
patients with null mutations have neonatal onset within 72 hours of birth
early onset patients are indistinguishable from those with carbamoyl phosphate synthetase i (cps1) deficiency
patients with residual enzyme activity have childhood or adult onset
can be effectively treated with n-carbamylglutamate


HPO:

32
n-acetylglutamate synthase deficiency:
Inheritance autosomal recessive inheritance


Classifications:

MalaCards categories:
Global: Genetic diseases Rare diseases Metabolic diseases
See all MalaCards categories (disease lists)
ICD10: 34
Orphanet: 59  
Inborn errors of metabolism


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Summaries for N-Acetylglutamate Synthase Deficiency

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NIH Rare Diseases : 53 N-acetylglutamate synthase deficiency (NAGS) is type of metabolic disorder that affects the processing of proteins and removal of ammonia from the body. When proteins are processed by the body, ammonia is formed. Individuals with NAGS are not able to remove ammonia from the body and have symptoms due to toxic levels of ammonia that build up in the blood. NAGS and other similar disorders are a type of metabolic condition known as a urea cycle disorder.  Signs and symptoms in newborns with NAGS may include a lack of energy, unwillingness to eat, seizures, unusual body movements, and poorly controlled breathing or body temperature. Complications may include coma, developmental delay, and learning disability. Some people have a less severe form of the deficiency with earliest symptoms manifesting later in life, particularly following high-protein meals, illness, or other stress. Signs and symptoms may include sudden vomiting, lack of coordination, confusion, and coma. NAGS is caused by mutations in the NAGS gene and is inherited in an autosomal recessive fashion. Treatment may include maintaining a low protein diet and using medications that provide alternative routes to remove ammonia from the body.

MalaCards based summary : N-Acetylglutamate Synthase Deficiency, also known as nags deficiency, is related to aspartylglucosaminuria and encephalopathy, and has symptoms including lethargy, seizures and respiratory distress. An important gene associated with N-Acetylglutamate Synthase Deficiency is NAGS (N-Acetylglutamate Synthase), and among its related pathways/superpathways is Arginine biosynthesis. The drugs Glutamic Acid and Vaccines have been mentioned in the context of this disorder. Related phenotypes are aggressive behavior and seizures

OMIM : 57 N-acetylglutamate synthase deficiency is an autosomal recessive disorder of the urea cycle. The clinical and biochemical features of the disorder are indistinguishable from carbamoyl phosphate synthase I deficiency (237300), since the CPS1 enzyme (608307) has an absolute requirement for NAGS (Caldovic et al., 2007). (237310)

UniProtKB/Swiss-Prot : 75 N-acetylglutamate synthase deficiency: Rare autosomal recessively inherited metabolic disorder leading to severe neonatal or late-onset hyperammonemia without increased excretion of orotic acid. Clinical symptoms are somnolence, tachypnea, feeding difficulties, a severe neurologic presentation characterized by uncontrollable movements, developmental delay, visual impairment, failure to thrive and hyperammonemia precipitated by the introduction of high-protein diet or febrile illness.

Genetics Home Reference : 25 N-acetylglutamate synthase deficiency is an inherited disorder that causes ammonia to accumulate in the blood. Ammonia, which is formed when proteins are broken down in the body, is toxic if the levels become too high. The nervous system is especially sensitive to the effects of excess ammonia.

Wikipedia : 76 N-Acetylglutamate synthase (or synthetase) deficiency is an autosomal recessive urea cycle... more...

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Related Diseases for N-Acetylglutamate Synthase Deficiency

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Diseases related to N-Acetylglutamate Synthase Deficiency via text searches within MalaCards or GeneCards Suite gene sharing:

# Related Disease Score Top Affiliating Genes
1 aspartylglucosaminuria 11.1
2 encephalopathy 10.3
3 movement disease 10.1
4 headache 10.1

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Symptoms & Phenotypes for N-Acetylglutamate Synthase Deficiency

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Symptoms via clinical synopsis from OMIM:

57
Neurologic Central Nervous System:
seizures
coma
lethargy
confusion
neurobehavioral changes associated with hyperammonemia
more
Respiratory:
respiratory distress

Laboratory Abnormalities:
hyperammonemia
increased serum glutamine
decreased or absent serum citrulline
normal urinary orotic acid

Growth Other:
failure to thrive

Neurologic Behavioral Psychiatric Manifestations:
aggressive behavior

Abdomen Gastrointestinal:
vomiting, recurrent


Clinical features from OMIM:

237310

Human phenotypes related to N-Acetylglutamate Synthase Deficiency:

32 (show all 11)
# Description HPO Frequency HPO Source Accession
1 aggressive behavior 32 HP:0000718
2 seizures 32 HP:0001250
3 lethargy 32 HP:0001254
4 coma 32 HP:0001259
5 confusion 32 HP:0001289
6 failure to thrive 32 HP:0001508
7 hyperammonemia 32 HP:0001987
8 vomiting 32 HP:0002013
9 respiratory distress 32 HP:0002098
10 cognitive impairment 32 HP:0100543
11 increased level of l-glutamic acid in blood 32 HP:0410068

UMLS symptoms related to N-Acetylglutamate Synthase Deficiency:


lethargy, seizures, respiratory distress, vomiting, recurrent

GenomeRNAi Phenotypes related to N-Acetylglutamate Synthase Deficiency according to GeneCards Suite gene sharing:

26
# Description GenomeRNAi Source Accession Score Top Affiliating Genes
1 Dynamic nuclei (hole, folded or small irregular) GR00257-A-1 8.8 NAGS SLC13A3 SLC22A6
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Drugs & Therapeutics for N-Acetylglutamate Synthase Deficiency

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Drugs for N-Acetylglutamate Synthase Deficiency (from DrugBank, HMDB, Dgidb, PharmGKB, IUPHAR, NovoSeek, BitterDB):


# Name Status Phase Clinical Trials Cas Number PubChem Id
1
Glutamic Acid Approved, Nutraceutical Phase 2 56-86-0 33032
2 Vaccines

Interventional clinical trials:


# Name Status NCT ID Phase Drugs
1 Long-term Outcome of N-Carbamylglutamate Treatment in Propionic Acidemia and Methylmalonic Acidemia Terminated NCT01597440 Phase 2 N-carbamylglutamate
2 The NIH UNI Study: Urea Cycle Disorders, Nutrition and Immunity Terminated NCT01421888

Search NIH Clinical Center for N-Acetylglutamate Synthase Deficiency

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Genetic Tests for N-Acetylglutamate Synthase Deficiency

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Genetic tests related to N-Acetylglutamate Synthase Deficiency:

# Genetic test Affiliating Genes
1 Hyperammonemia, Type Iii 29 NAGS
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Anatomical Context for N-Acetylglutamate Synthase Deficiency

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Publications for N-Acetylglutamate Synthase Deficiency

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Articles related to N-Acetylglutamate Synthase Deficiency:

(show all 20)
# Title Authors Year
1
Late-Onset N-Acetylglutamate Synthase Deficiency: Report of a Paradigmatic Adult Case Presenting with Headaches and Review of the Literature. ( 29364180 )
2018
2
Hyperammonemia due to Adult-Onset N-Acetylglutamate Synthase Deficiency. ( 27147233 )
2016
3
N-acetylglutamate synthase deficiency: Novel mutation associated with neonatal presentation and literature review of molecular and phenotypic spectra. ( 27570737 )
2016
4
A commentary on short-term efficacy of N-carbamylglutamate in a patient with N-acetylglutamate synthase deficiency. ( 25994872 )
2015
5
Short-term efficacy of N-carbamylglutamate in a patient with N-acetylglutamate synthase deficiency. ( 25787344 )
2015
6
Low Dose of Carglumic Acid for Treatment of Hyperammonemia due to N-Acetylglutamate Synthase Deficiency. ( 25228620 )
2014
7
Transporters involved in renal excretion of N-carbamoylglutamate, an orphan drug to treat inborn N-acetylglutamate synthase deficiency. ( 25354943 )
2014
8
Recurrent encephalopathy: NAGS (N-acetylglutamate synthase) deficiency in adults. ( 23250120 )
2013
9
N-acetylglutamate synthase deficiency: an insight into the genetics, epidemiology, pathophysiology, and treatment. ( 23776373 )
2011
10
Role of carglumic acid in the treatment of acute hyperammonemia due to N-acetylglutamate synthase deficiency. ( 21941437 )
2011
11
Favourable long-term outcome after immediate treatment of neonatal hyperammonemia due to N-acetylglutamate synthase deficiency. ( 19533169 )
2010
12
Polar body-based preimplantation genetic diagnosis for N-acetylglutamate synthase deficiency. ( 18753752 )
2008
13
Misleading diagnosis of partial N-acetylglutamate synthase deficiency based on enzyme measurement corrected by mutation analysis. ( 15858972 )
2005
14
Late onset N-acetylglutamate synthase deficiency caused by hypomorphic alleles. ( 15714518 )
2005
15
Restoration of ureagenesis in N-acetylglutamate synthase deficiency by N-carbamylglutamate. ( 15480384 )
2004
16
Mutation analysis in patients with N-acetylglutamate synthase deficiency. ( 12754705 )
2003
17
Diagnosis of N-acetylglutamate synthase deficiency by use of cultured fibroblasts and avoidance of nonsense-mediated mRNA decay. ( 14605506 )
2003
18
N-acetylglutamate synthase deficiency and the treatment of hyperammonemic encephalopathy. ( 12447942 )
2002
19
A 6-year-old boy with hyperammonaemia: partial N-acetylglutamate synthase deficiency or portosystemic encephalopathy? ( 11131349 )
2000
20
A new neonatal case of N-acetylglutamate synthase deficiency treated by carbamylglutamate. ( 7623444 )
1995
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Variations for N-Acetylglutamate Synthase Deficiency

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UniProtKB/Swiss-Prot genetic disease variations for N-Acetylglutamate Synthase Deficiency:

75
# Symbol AA change Variation ID SNP ID
1 NAGS p.Cys200Arg VAR_023505
2 NAGS p.Ala279Pro VAR_023506
3 NAGS p.Ser410Pro VAR_023507
4 NAGS p.Leu430Pro VAR_023508 rs104894605
5 NAGS p.Trp484Arg VAR_023509 rs104894606
6 NAGS p.Ala518Thr VAR_023510 rs745511282

ClinVar genetic disease variations for N-Acetylglutamate Synthase Deficiency:

6
(show top 50) (show all 56)
# Gene Variation Type Significance SNP ID Assembly Location
1 NAGS NM_153006.2(NAGS): c.1025delG (p.Arg342Profs) deletion Pathogenic rs730880266 GRCh38 Chromosome 17, 44006638: 44006638
2 NAGS NM_153006.2(NAGS): c.1025delG (p.Arg342Profs) deletion Pathogenic rs730880266 GRCh37 Chromosome 17, 42084006: 42084006
3 NAGS NM_153006.2(NAGS): c.971G> A (p.Trp324Ter) single nucleotide variant Pathogenic rs104894604 GRCh37 Chromosome 17, 42083952: 42083952
4 NAGS NM_153006.2(NAGS): c.971G> A (p.Trp324Ter) single nucleotide variant Pathogenic rs104894604 GRCh38 Chromosome 17, 44006584: 44006584
5 NAGS NM_153006.2(NAGS): c.916-2A> T single nucleotide variant Pathogenic rs730880267 GRCh38 Chromosome 17, 44006527: 44006527
6 NAGS NM_153006.2(NAGS): c.916-2A> T single nucleotide variant Pathogenic rs730880267 GRCh37 Chromosome 17, 42083895: 42083895
7 NAGS NM_153006.2(NAGS): c.1307dupT (p.Thr439Hisfs) duplication Pathogenic rs730880303 GRCh38 Chromosome 17, 44007629: 44007629
8 NAGS NM_153006.2(NAGS): c.1307dupT (p.Thr439Hisfs) duplication Pathogenic rs730880303 GRCh37 Chromosome 17, 42084997: 42084997
9 NAGS NM_153006.2(NAGS): c.835G> A (p.Ala279Thr) single nucleotide variant Pathogenic rs121912591 GRCh37 Chromosome 17, 42083525: 42083525
10 NAGS NM_153006.2(NAGS): c.835G> A (p.Ala279Thr) single nucleotide variant Pathogenic rs121912591 GRCh38 Chromosome 17, 44006157: 44006157
11 NAGS NM_153006.2(NAGS): c.1289T> C (p.Leu430Pro) single nucleotide variant Pathogenic rs104894605 GRCh37 Chromosome 17, 42084979: 42084979
12 NAGS NM_153006.2(NAGS): c.1289T> C (p.Leu430Pro) single nucleotide variant Pathogenic rs104894605 GRCh38 Chromosome 17, 44007611: 44007611
13 NAGS NM_153006.2(NAGS): c.1450T> C (p.Trp484Arg) single nucleotide variant Pathogenic rs104894606 GRCh37 Chromosome 17, 42085140: 42085140
14 NAGS NM_153006.2(NAGS): c.1450T> C (p.Trp484Arg) single nucleotide variant Pathogenic rs104894606 GRCh38 Chromosome 17, 44007772: 44007772
15 NAGS NM_153006.2(NAGS): c.1299G> C (p.Glu433Asp) single nucleotide variant Pathogenic rs104894607 GRCh37 Chromosome 17, 42084989: 42084989
16 NAGS NM_153006.2(NAGS): c.1299G> C (p.Glu433Asp) single nucleotide variant Pathogenic rs104894607 GRCh38 Chromosome 17, 44007621: 44007621
17 NAGS NM_153006.2(NAGS): c.182A> G (p.Glu61Gly) single nucleotide variant Benign/Likely benign rs113134544 GRCh37 Chromosome 17, 42082213: 42082213
18 NAGS NM_153006.2(NAGS): c.182A> G (p.Glu61Gly) single nucleotide variant Benign/Likely benign rs113134544 GRCh38 Chromosome 17, 44004845: 44004845
19 NAGS NM_153006.2(NAGS): c.1086T> C (p.Phe362=) single nucleotide variant Benign rs55708447 GRCh37 Chromosome 17, 42084067: 42084067
20 NAGS NM_153006.2(NAGS): c.1086T> C (p.Phe362=) single nucleotide variant Benign rs55708447 GRCh38 Chromosome 17, 44006699: 44006699
21 NAGS NM_153006.2(NAGS): c.1096+20C> G single nucleotide variant Benign rs228771 GRCh38 Chromosome 17, 44006729: 44006729
22 NAGS NM_153006.2(NAGS): c.1096+20C> G single nucleotide variant Benign rs228771 GRCh37 Chromosome 17, 42084097: 42084097
23 NAGS NM_153006.2(NAGS): c.1451+9T> C single nucleotide variant Benign rs228773 GRCh37 Chromosome 17, 42085150: 42085150
24 NAGS NM_153006.2(NAGS): c.1451+9T> C single nucleotide variant Benign rs228773 GRCh38 Chromosome 17, 44007782: 44007782
25 NAGS NM_153006.2(NAGS): c.*3C> T single nucleotide variant Benign rs186636 GRCh38 Chromosome 17, 44008604: 44008604
26 NAGS NM_153006.2(NAGS): c.*3C> T single nucleotide variant Benign rs186636 GRCh37 Chromosome 17, 42085972: 42085972
27 NAGS NM_153006.2(NAGS): c.1323C> G (p.Tyr441Ter) single nucleotide variant Pathogenic rs886042831 GRCh37 Chromosome 17, 42085013: 42085013
28 NAGS NM_153006.2(NAGS): c.1323C> G (p.Tyr441Ter) single nucleotide variant Pathogenic rs886042831 GRCh38 Chromosome 17, 44007645: 44007645
29 NAGS NM_153006.2(NAGS): c.904A> G (p.Ser302Gly) single nucleotide variant Uncertain significance rs377702343 GRCh38 Chromosome 17, 44006226: 44006226
30 NAGS NM_153006.2(NAGS): c.904A> G (p.Ser302Gly) single nucleotide variant Uncertain significance rs377702343 GRCh37 Chromosome 17, 42083594: 42083594
31 NAGS NM_153006.2(NAGS): c.1231C> A (p.Leu411Met) single nucleotide variant Uncertain significance rs199923863 GRCh38 Chromosome 17, 44007457: 44007457
32 NAGS NM_153006.2(NAGS): c.1231C> A (p.Leu411Met) single nucleotide variant Uncertain significance rs199923863 GRCh37 Chromosome 17, 42084825: 42084825
33 NAGS NM_153006.2(NAGS): c.1281C> G (p.Ala427=) single nucleotide variant Uncertain significance rs371886833 GRCh38 Chromosome 17, 44007603: 44007603
34 NAGS NM_153006.2(NAGS): c.1281C> G (p.Ala427=) single nucleotide variant Uncertain significance rs371886833 GRCh37 Chromosome 17, 42084971: 42084971
35 NAGS NM_153006.2(NAGS): c.1398G> A (p.Arg466=) single nucleotide variant Conflicting interpretations of pathogenicity rs369492320 GRCh38 Chromosome 17, 44007720: 44007720
36 NAGS NM_153006.2(NAGS): c.1398G> A (p.Arg466=) single nucleotide variant Conflicting interpretations of pathogenicity rs369492320 GRCh37 Chromosome 17, 42085088: 42085088
37 NAGS NM_153006.2(NAGS): c.1268+11G> A single nucleotide variant Conflicting interpretations of pathogenicity rs201629145 GRCh38 Chromosome 17, 44007505: 44007505
38 NAGS NM_153006.2(NAGS): c.1268+11G> A single nucleotide variant Conflicting interpretations of pathogenicity rs201629145 GRCh37 Chromosome 17, 42084873: 42084873
39 NAGS NM_153006.2(NAGS): c.1302C> T (p.Pro434=) single nucleotide variant Conflicting interpretations of pathogenicity rs150004962 GRCh38 Chromosome 17, 44007624: 44007624
40 NAGS NM_153006.2(NAGS): c.1302C> T (p.Pro434=) single nucleotide variant Conflicting interpretations of pathogenicity rs150004962 GRCh37 Chromosome 17, 42084992: 42084992
41 NAGS NM_153006.2(NAGS): c.116C> T (p.Ala39Val) single nucleotide variant Uncertain significance rs754480096 GRCh38 Chromosome 17, 44004779: 44004779
42 NAGS NM_153006.2(NAGS): c.116C> T (p.Ala39Val) single nucleotide variant Uncertain significance rs754480096 GRCh37 Chromosome 17, 42082147: 42082147
43 NAGS NM_153006.2(NAGS): c.681C> G (p.Ala227=) single nucleotide variant Uncertain significance rs886052982 GRCh38 Chromosome 17, 44005891: 44005891
44 NAGS NM_153006.2(NAGS): c.681C> G (p.Ala227=) single nucleotide variant Uncertain significance rs886052982 GRCh37 Chromosome 17, 42083259: 42083259
45 NAGS NM_153006.2(NAGS): c.807C> T (p.Ser269=) single nucleotide variant Uncertain significance rs767368629 GRCh38 Chromosome 17, 44006129: 44006129
46 NAGS NM_153006.2(NAGS): c.807C> T (p.Ser269=) single nucleotide variant Uncertain significance rs767368629 GRCh37 Chromosome 17, 42083497: 42083497
47 NAGS NM_153006.2(NAGS): c.*211C> T single nucleotide variant Benign rs640631 GRCh38 Chromosome 17, 44008812: 44008812
48 NAGS NM_153006.2(NAGS): c.*211C> T single nucleotide variant Benign rs640631 GRCh37 Chromosome 17, 42086180: 42086180
49 NAGS NM_153006.2(NAGS): c.374C> A (p.Thr125Lys) single nucleotide variant Likely benign rs185863881 GRCh37 Chromosome 17, 42082405: 42082405
50 NAGS NM_153006.2(NAGS): c.374C> A (p.Thr125Lys) single nucleotide variant Likely benign rs185863881 GRCh38 Chromosome 17, 44005037: 44005037
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Expression for N-Acetylglutamate Synthase Deficiency

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Search GEO for disease gene expression data for N-Acetylglutamate Synthase Deficiency.
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Pathways for N-Acetylglutamate Synthase Deficiency

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Pathways related to N-Acetylglutamate Synthase Deficiency according to KEGG:

37
# Name Kegg Source Accession
1 Arginine biosynthesis hsa00220
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GO Terms for N-Acetylglutamate Synthase Deficiency

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Biological processes related to N-Acetylglutamate Synthase Deficiency according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 transmembrane transport GO:0055085 8.96 SLC13A3 SLC22A6
2 anion transmembrane transport GO:0098656 8.62 SLC13A3 SLC22A6
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Sources for N-Acetylglutamate Synthase Deficiency

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3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 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 SNOMED-CT via Orphanet
71 TGDB
72 Tocris
73 UMLS
74 UMLS via Orphanet
The MalaCards human disease database index: 1-9 A B C D E F G H I J K L M N O P Q R S T U V W X Y Z
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