Ornithine transcarbamylase deficiency

General Information (adopted from Orphanet):

Synonyms, Signs: OTC deficency
OCT deficiency
OTC deficiency valporate sensitivity, included
ornithine carbamoyltransferase deficiency
Number of Symptoms 61
OrphanetNr: 664
OMIM Id: 311250
ICD-10: E72.2
UMLs: C0268542
MeSH: D020163
MedDRA: 10052450
Snomed: 80908008

Prevalence, inheritance and age of onset:

Prevalence: < 2 of 100 000 - PMID: 20142522 [IBIS]
Inheritance: X-linked
- PMID: 10064660 [IBIS]
Age of onset: Neonatal
Infancy
Childhood
Adult
- PMID: 18647279; 3661651 [IBIS]

Disease classification (adopted from Orphanet):

Parent Diseases: Disorder of urea cycle metabolism and ammonia detoxification
 -Rare genetic disease
Syndromic neurometabolic disease with X-linked intellectual deficit
 -Rare genetic disease
 -Rare neurologic disease

Comment:

Ornithine transcarbamylase deficiency belongs to the class of urea cycle disorders and is caused by mutations in the gene OTC encoding the enzyme ornithine transcarbamylase. OTC deficiency is among urea cycle disorders the most common disorder. Mutations can be divided into two groups: those with neonatal onset with all enzyme activity abolished, and those with later onset with partial and varying enzyme deficiency. Since OTC gene is located on the short arm of the X chromosome (Xp21.1), boys are most severely affected, with heterozygote girls tending to have milder symptoms (PMID:12788037).

Symptom Information: Sort by abundance 

1
 (MedDRA:10052450) Ornithine transcarbamoylase deficiency Very frequent [IBIS] 12788037 IBIS 1 / 7739
2
 (HPO:0002027) Abdominal pain 21926883 IBIS 184 / 7739
3
 (HPO:0002039) Anorexia 23790482 IBIS 62 / 7739
4
 (HPO:0008872) Feeding difficulties in infancy 12788037 IBIS 153 / 7739
5
 (HPO:0002013) Vomiting Very frequent [IBIS] 25011434 IBIS 191 / 7739
6
 (HPO:0002038) Protein avoidance 12788037 IBIS 7 / 7739
7
 (HPO:0000505) Visual impairment 3661651 IBIS 297 / 7739
8
 (HPO:0100704) Cortical visual impairment Rare [IBIS] 24850570 IBIS 28 / 7739
9
 (HPO:0002098) Respiratory distress 12788037 IBIS 75 / 7739
10
 (HPO:0003218) Oroticaciduria Frequent [IBIS] 25994866 IBIS 10 / 7739
11
 (HPO:0001950) Respiratory alkalosis 12788037 IBIS 7 / 7739
12
 (HPO:0001508) Failure to thrive 6842197 IBIS 454 / 7739
13
 (HPO:0004337) Abnormality of amino acid metabolism Very frequent [IBIS] Very frequent [Orphanet] 25011434 IBIS 45 / 7739
14
 (HPO:0003572) Low plasma citrulline Very frequent [IBIS] 25011434 IBIS 7 / 7739
15
 (HPO:0005961) Hypoargininemia 25011434 IBIS 7 / 7739
16
 (HPO:0003217) Hyperglutaminemia Very frequent [IBIS] 25011434 IBIS 9 / 7739
17
 (HPO:0003348) Hyperalaninemia 12788037 IBIS 19 / 7739
18
 (HPO:0003355) Aminoaciduria Very frequent [IBIS] Very frequent [Orphanet] 24006547 IBIS 65 / 7739
19
 (HPO:0003532) Ornithinuria Very frequent [IBIS] 24006547 IBIS 5 / 7739
20
 (HPO:0002181) Cerebral edema 12788037; 24616362 IBIS 19 / 7739
21
 (HPO:0100806) Sepsis 10064660 IBIS 48 / 7739
22
 (HPO:0001987) Hyperammonemia Very frequent [IBIS] Very frequent [Orphanet] 25994866 IBIS 50 / 7739
23
 (HPO:0001252) Muscular hypotonia Frequent [IBIS] 21989980 IBIS 990 / 7739
24
 (HPO:0001298) Encephalopathy Frequent [IBIS] 25011434 IBIS 72 / 7739
25
 (HPO:0001251) Ataxia 12788037 IBIS 413 / 7739
26
 (HPO:0002075) Dysdiadochokinesis 23790482 IBIS 40 / 7739
27
 (HPO:0001310) Dysmetria 23790482 IBIS 76 / 7739
28
 (HPO:0002131) Episodic ataxia 12788037 IBIS 16 / 7739
29
 (HPO:0001285) Spastic tetraparesis Frequent [IBIS] 10064660 IBIS 29 / 7739
30
 (HPO:0002301) Hemiplegia Occasional [IBIS] 12788037 IBIS 42 / 7739
31
 (HPO:0100021) Cerebral palsy 10064660 IBIS 36 / 7739
32
 (HPO:0000708) Behavioral abnormality 12788037 IBIS 212 / 7739
33
 (HPO:0001289) Confusion 12788037 IBIS 36 / 7739
34
 (HPO:0001263) Global developmental delay 10064660 IBIS 853 / 7739
35
 (HPO:0001249) Intellectual disability Frequent [IBIS] 24006547 IBIS 1089 / 7739
36
 (HPO:0001270) Motor delay 24881970 IBIS 322 / 7739
37
 (HPO:0000737) Irritability 10064660 IBIS 93 / 7739
38
 (HPO:0001254) Lethargy 12788037 IBIS 104 / 7739
39
 (HPO:0001259) Coma Frequent [IBIS] 25011434 IBIS 65 / 7739
40
 (HPO:0001262) Somnolence 22727265 IBIS 20 / 7739
41
 (HPO:0100543) Cognitive impairment 25135652 IBIS 230 / 7739
42
 (HPO:0002516) Increased intracranial pressure 24616362 IBIS 47 / 7739
43
 (HPO:0012164) Asterixis 23790482 IBIS 1 / 7739
44
 (HPO:0001288) Gait disturbance 23790482 IBIS 318 / 7739
45
 (HPO:0001337) Tremor 23790482 IBIS 200 / 7739
46
 (HPO:0002315) Headache 12788037 IBIS 175 / 7739
47
 (HPO:0002353) EEG abnormality 12788037 IBIS 188 / 7739
48
 (HPO:0001250) Seizures Very frequent [IBIS] 25011434 IBIS 1245 / 7739
49
 (HPO:0001951) Episodic ammonia intoxication 2035531 IBIS 4 / 7739
50
 (HPO:0012127) Uraciluria 12788037 IBIS 2 / 7739
51
 (HPO:0002045) Hypothermia Occasional [IBIS] 21989980 IBIS 27 / 7739
52
 (HPO:0001410) Decreased liver function Very frequent [IBIS] Very frequent [Orphanet] 25135652 IBIS 59 / 7739
53
 (HPO:0001399) Hepatic failure Frequent [IBIS] Very frequent [Orphanet] 25135652; 24006547 IBIS 80 / 7739
54
 (HPO:0001733) Pancreatitis Occasional [IBIS] 12788037 IBIS 46 / 7739
55
 (HPO:0001297) Stroke 24850570 IBIS 44 / 7739
56
 (HPO:0002883) Hyperventilation 12788037 IBIS 10 / 7739
57
 (HPO:0002789) Tachypnea 23790482 IBIS 48 / 7739
58
 (HPO:0001510) Growth delay 16703326 IBIS 295 / 7739
59
 (OMIM) Hepatic ornithine transcarbamylase deficiency 12788037 IBIS 1 / 7739
60
 (OMIM) High ornithine 24006547 IBIS 1 / 7739
61
 (OMIM) High plasma asparagine 20142522 IBIS 1 / 7739

Associated genes:

OTC;

ClinVar (via SNiPA)

Gene symbol Variation Clinical significance Reference

Additional Information:

Description: (OMIM) Ornithine transcarbamylase deficiency is an X-linked inborn error of metabolism of the urea cycle which causes hyperammonemia. The disorder is treatable with supplemental dietary arginine and low protein diet.

Urea cycle disorders are characterized by the ...
Diagnosis OMIM Rowe et al. (1986) suggested that family history, dietary history, episodic nonspecific symptoms, response to withdrawal of protein, and other characteristics should permit early diagnosis. In 5 patients tested, IQ was below 70 at the time of diagnosis. ...
Clinical Description OMIM Russell et al. (1962) described 2 cousins with chronic ammonia intoxication and mental deterioration. By liver biopsy, the activity of hepatic OTC was shown to be very low. A defect was presumed to be present in urea synthesis ...
Genotype-Phenotype Correlations OMIM McCullough et al. (2000) examined the genotype/phenotype correlations of 157 probands with OTC deficiency, including 57 heterozygous females. In patients with mutations that abolished enzyme activity, the severe clinical and biochemical phenotype was homogeneous. The males in this ...
Molecular genetics OMIM Rozen et al. (1985) gave the first reported example of an OTC gene deletion that could be identified cytogenetically in a patient with OTC deficiency. In a boy with a mild form of OTC deficiency, Maddalena et al. ...
Population genetics OMIM Nagata et al. (1991) estimated that OTC deficiency has a frequency of 1 in 80,000 births in Japan. The total frequency of this and the other urea cycle enzymopathies, carbamoyl phosphate synthetase deficiency, argininosuccinate synthetase deficiency, argininosuccinate lyase ...