Hyperammonemia due to N-acetylglutamate synthetase deficiency

General Information (adopted from Orphanet):

Synonyms, Signs: NAGS deficiency
N-acetylglutamate synthetase deficiency
Number of Symptoms 48
OrphanetNr: 927
OMIM Id: 237310
ICD-10: E72.2
UMLs:
MeSH:
MedDRA:
Snomed:

Prevalence, inheritance and age of onset:

Prevalence: < 60 cases - PMID: 27037498 [IBIS]
Inheritance: Autosomal recessive
- PMID: 27037498 [IBIS]
Age of onset: Neonatal
Adult
- PMID: 24233332; 23250120 [IBIS]

Disease classification (adopted from Orphanet):

Parent Diseases: Disorder of urea cycle metabolism and ammonia detoxification
 -Rare genetic disease

Comment:

N-acetylglutamate synthetase deficiency belongs to the class of urea cycle disorders and is caused by mutations in the gene NAGS encoding the enzyme N-acetylglutamate synthetase. It is one of the rarest urea cycle diseases with clinical and biochemical features identical to those seen in CPS1 deficiency (PMID:27037498). Unlike in OTC deficiency, urinary orotic acid is not elevated (PMID:23776373).

Symptom Information: Sort by abundance 

1
(HPO:0002039) Anorexia 23776373 IBIS 62 / 7739
2
(HPO:0002014) Diarrhea 23776373 IBIS 225 / 7739
3
(HPO:0011968) Feeding difficulties 23776373 IBIS 240 / 7739
4
(HPO:0002018) Nausea 23776373 IBIS 44 / 7739
5
(HPO:0002013) Vomiting Frequent [IBIS] 23776373; 12942317 IBIS 191 / 7739
6
(HPO:0002038) Protein avoidance 9877039 IBIS 7 / 7739
7
(HPO:0002248) Hematemesis 1779615 IBIS 12 / 7739
8
(HPO:0000505) Visual impairment 18753752 IBIS 297 / 7739
9
(HPO:0002098) Respiratory distress 23776373 IBIS 75 / 7739
10
(HPO:0001942) Metabolic acidosis Occasional [IBIS] 1779615 IBIS 81 / 7739
11
(HPO:0001508) Failure to thrive 18753752 IBIS 454 / 7739
12
(HPO:0003572) Low plasma citrulline 23776373 IBIS 7 / 7739
13
(HPO:0005961) Hypoargininemia 1779615 IBIS 7 / 7739
14
(HPO:0003217) Hyperglutaminemia 23776373; 9877039 IBIS 9 / 7739
15
(HPO:0004755) Supraventricular tachycardia 24233332 IBIS 20 / 7739
16
(HPO:0002181) Cerebral edema 12942317 IBIS 19 / 7739
17
(HPO:0001987) Hyperammonemia Very frequent [IBIS] 21941437 IBIS 50 / 7739
18
(HPO:0001298) Encephalopathy 23250120 IBIS 72 / 7739
19
(HPO:0001251) Ataxia 23776373 IBIS 413 / 7739
20
(HPO:0010550) Paraplegia 23776373 IBIS 10 / 7739
21
(HPO:0000708) Behavioral abnormality 23776373; 9877039 IBIS 212 / 7739
22
(HPO:0000711) Restlessness 23776373 IBIS 18 / 7739
23
(HPO:0000718) Aggressive behavior 23776373 IBIS 109 / 7739
24
(HPO:0000739) Anxiety 23776373; 12942317 IBIS 67 / 7739
25
(HPO:0001289) Confusion 23776373; 12942317 IBIS 36 / 7739
26
(HPO:0002361) Psychomotor deterioration 23776373 IBIS 26 / 7739
27
(HPO:0001263) Global developmental delay 18753752 IBIS 853 / 7739
28
(HPO:0001249) Intellectual disability 23776373 IBIS 1089 / 7739
29
(HPO:0000737) Irritability 23776373; 12942317 IBIS 93 / 7739
30
(HPO:0001254) Lethargy Frequent [IBIS] 23776373 IBIS 104 / 7739
31
(HPO:0001259) Coma Frequent [IBIS] 23776373 IBIS 65 / 7739
32
(HPO:0002329) Drowsiness 23776373 IBIS 19 / 7739
33
(HPO:0000709) Psychosis 12942317 IBIS 61 / 7739
34
(HPO:0001262) Somnolence 23776373 IBIS 20 / 7739
35
(HPO:0100543) Cognitive impairment 23776373 IBIS 230 / 7739
36
(HPO:0001337) Tremor 23776373; 12942317 IBIS 200 / 7739
37
(HPO:0002315) Headache 23776373; 12942317 IBIS 175 / 7739
38
(HPO:0002076) Migraine 23776373 IBIS 41 / 7739
39
(HPO:0002353) EEG abnormality 12942317 IBIS 188 / 7739
40
(HPO:0001250) Seizures Frequent [IBIS] 23776373 IBIS 1245 / 7739
41
(HPO:0001399) Hepatic failure Occasional [IBIS] 1779615 IBIS 80 / 7739
42
(HPO:0002240) Hepatomegaly 23776373 IBIS 467 / 7739
43
(HPO:0002789) Tachypnea 23776373 IBIS 48 / 7739
44
(HPO:0001510) Growth delay 18516804 IBIS 295 / 7739
45
(MedDRA:10041953) Staring 23776373 IBIS 5 / 7739
46
(OMIM) Neurobehavioral changes associated with hyperammonemia 23776373 IBIS 1 / 7739
47
(OMIM) Normal urinary orotic acid 23776373 IBIS 1 / 7739
48
(OMIM) [DEL]Increased serum glutamine 23776373 IBIS 1 / 7739

Associated genes:

NAGS;

ClinVar (via SNiPA)

Gene symbol Variation Clinical significance Reference

Additional Information:

Description: (OMIM) 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 ...
Clinical Description OMIM Bachmann et al. (1981) reported hyperammonemia due to deficiency of N-acetylglutamate synthetase in a newborn male and presumably in 2 of his sibs who died in the neonatal period. Autopsy in 1 of the sibs suggested hyperammonemia. The ...
Molecular genetics OMIM In each of 2 patients with NAGS deficiency, Caldovic et al. (2003) identified a homozygous mutation in the NAGS gene (608300.0001-608300.0002). In 6 families with NAGS deficiency, Haberle et al. (2003) identified 7 mutations in the NAGS gene ...