Carbamoylphosphate synthetase deficiency

General Information (adopted from Orphanet):

Synonyms, Signs: CPSD
Carbamoyl phosphate synthetase 1 deficiency
CPS1 deficiency
Number of Symptoms 53
OrphanetNr: 147
OMIM Id: 237300
ICD-10: E72.2
UMLs:
MeSH:
MedDRA: 10058297
Snomed:

Prevalence, inheritance and age of onset:

Prevalence: <= 0.5 of 100 000 - PMID: 20142522 [IBIS]
Inheritance: Autosomal recessive
- PMID: 26440671 [IBIS]
Age of onset: Neonatal
Childhood
- PMID: 26440671 [IBIS]

Disease classification (adopted from Orphanet):

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

Comment:

Carbamoylphosphate synthetase deficiency belongs to the class of urea cycle disorders. It is caused by deficiency of the enzyme carbamoylphosphate synthetase (CPS1), one of the six enzymes and two transporters involved in the detoxification of ammonium to urea. Since CPS1 enzyme has an absolute requirement for N-acetylglutamat, the clinical and biochemical features of CPS1 deficiency are indistinguishable from N-acetylglutamate-deficiency (PMID:27037498). Two distinct CPS1 deficiency clinical phenotypes can be identified: neonatal onset and late onset (PMID:19167850).

Symptom Information: Sort by abundance 

1
 (HPO:0008872) Feeding difficulties in infancy Frequent [IBIS] 19167850 IBIS 153 / 7739
2
 (HPO:0002033) Poor suck Frequent [IBIS] 26440671 IBIS 37 / 7739
3
 (HPO:0002018) Nausea 21837743 IBIS 44 / 7739
4
 (HPO:0002013) Vomiting Frequent [IBIS] 6485804 IBIS 191 / 7739
5
 (HPO:0002038) Protein avoidance 21837743 IBIS 7 / 7739
6
 (HPO:0002093) Respiratory insufficiency Very frequent [Orphanet] 12055368 IBIS 410 / 7739
7
 (HPO:0002094) Dyspnea Very frequent [Orphanet] 12055368 IBIS 132 / 7739
8
 (HPO:0002098) Respiratory distress Very frequent [Orphanet] 12055368 IBIS 75 / 7739
9
 (HPO:0200114) Metabolic alkalosis 2745145 IBIS 6 / 7739
10
 (HPO:0001950) Respiratory alkalosis Frequent [IBIS] 19167850 IBIS 7 / 7739
11
 (HPO:0001508) Failure to thrive 26440671 IBIS 454 / 7739
12
 (HPO:0001531) Failure to thrive in infancy 4641111 IBIS 26 / 7739
13
 (HPO:0004337) Abnormality of amino acid metabolism Very frequent [IBIS] Very frequent [Orphanet] 26440671 IBIS 45 / 7739
14
 (HPO:0003572) Low plasma citrulline Very frequent [IBIS] 20800523 IBIS 7 / 7739
15
 (HPO:0005961) Hypoargininemia 6511918 IBIS 7 / 7739
16
 (HPO:0003217) Hyperglutaminemia Frequent [IBIS] 20800523 IBIS 9 / 7739
17
 (HPO:0003348) Hyperalaninemia 8273985 IBIS 19 / 7739
18
 (MedDRA:10058297) Carbamoyl phosphate synthetase deficiency Very frequent [IBIS] 8273985 IBIS 1 / 7739
19
 (HPO:0001649) Tachycardia 2745145 IBIS 53 / 7739
20
 (HPO:0002181) Cerebral edema 2974563 IBIS 19 / 7739
21
 (HPO:0001987) Hyperammonemia Very frequent [IBIS] Very frequent [Orphanet] 20800523 IBIS 50 / 7739
22
 (HPO:0001252) Muscular hypotonia Frequent [IBIS] Very frequent [Orphanet] 6438391 IBIS 990 / 7739
23
 (HPO:0001324) Muscle weakness Very frequent [Orphanet] hallmark [HPO] 6438391 IBIS 859 / 7739
24
 (HPO:0003484) Upper limb muscle weakness 21837743 IBIS 19 / 7739
25
 (HPO:0003326) Myalgia 21837743 IBIS 143 / 7739
26
 (HPO:0200134) Epileptic encephalopathy 1414247 IBIS 42 / 7739
27
 (HPO:0001251) Ataxia 7252721 IBIS 413 / 7739
28
 (HPO:0002509) Limb hypertonia 26440671 IBIS 13 / 7739
29
 (HPO:0000712) Emotional lability 21837743 IBIS 44 / 7739
30
 (HPO:0000713) Agitation 8273985 IBIS 18 / 7739
31
 (HPO:0000741) Apathy 21837743 IBIS 42 / 7739
32
 (HPO:0001260) Dysarthria 21837743 IBIS 329 / 7739
33
 (HPO:0001289) Confusion 8273985 IBIS 36 / 7739
34
 (HPO:0001263) Global developmental delay Frequent [IBIS] 7252721 IBIS 853 / 7739
35
 (HPO:0001249) Intellectual disability 7252721 IBIS 1089 / 7739
36
 (HPO:0000737) Irritability 2745145 IBIS 93 / 7739
37
 (HPO:0001254) Lethargy Frequent [IBIS] 7252721 IBIS 104 / 7739
38
 (HPO:0001259) Coma Frequent [IBIS] 8273985 IBIS 65 / 7739
39
 (HPO:0000751) Personality changes 21837743 IBIS 33 / 7739
40
 (HPO:0001262) Somnolence 19167850 IBIS 20 / 7739
41
 (HPO:0002533) Abnormal posturing 8273985 IBIS 6 / 7739
42
 (HPO:0200085) Limb tremor 21837743 IBIS 6 / 7739
43
 (HPO:0001250) Seizures Frequent [IBIS] Very frequent [Orphanet] 8273985 IBIS 1245 / 7739
44
 (HPO:0002045) Hypothermia Frequent [IBIS] 26440671 IBIS 27 / 7739
45
 (HPO:0002104) Apnea 26440671 IBIS 106 / 7739
46
 (HPO:0100520) Oliguria 6485804 IBIS 14 / 7739
47
 (HPO:0001297) Stroke 21837743 IBIS 44 / 7739
48
 (HPO:0000873) Diabetes insipidus 8273985 IBIS 34 / 7739
49
 (HPO:0002789) Tachypnea 19167850 IBIS 48 / 7739
50
 (HPO:0001510) Growth delay 7252721 IBIS 295 / 7739
51
 (HPO:0002059) Cerebral atrophy 1414247 IBIS 171 / 7739
52
 (MedDRA:10073346) Decerebrate posture 8273985 IBIS 2 / 7739
53
 (OMIM) Low urinary orotic acid Frequent [IBIS] 4641111 IBIS 1 / 7739

Associated genes:

CPS1;

ClinVar (via SNiPA)

Gene symbol Variation Clinical significance Reference

Additional Information:

Description: (OMIM) Carbamoyl phosphate synthetase I deficiency is an autosomal recessive inborn error of metabolism of the urea cycle which causes hyperammonemia. There are 2 main forms: a lethal neonatal type and a less severe, delayed-onset type (summary by Klaus ...
Diagnosis OMIM - Prenatal Diagnosis

By chorionic villus sampling, Finckh et al. (1998) diagnosed a 12-week-old fetus with CPS I deficiency. Pathologic examination of the fetal liver showed hepatocellular changes consistent with the disorder.
Clinical Description OMIM - Early-Onset Form

This disorder was first reported by Freeman et al. (1970) in a patient with congenital hyperammonemia and decreased levels of carbamoyl phosphate synthetase. A family with 3 affected sibs was reported by Hommes ...
Genotype-Phenotype Correlations OMIM Klaus et al. (2009) reported a man and his grandson, who were of Lebanese origin, with variable clinical manifestations of CPS I deficiency despite having the same genotype. The man presented at age 45 years with episodes of ...
Molecular genetics OMIM In a newborn Japanese girl with CPS I deficiency (237300), Hoshide et al. (1993) identified a homozygous missense mutation in the CPS1 gene (608307.0001).

In 16 of 18 Japanese patients with a clinical diagnosis of CPS ...
Population genetics OMIM Nagata et al. (1991) estimated that the incidence of CPS I deficiency in Japan is 1 in 800,000.

The prevalence of CPS I deficiency is estimated to be between 1 in 200,000 to 1 in 800,000 ...