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OTCD
MCID: ORN008
MIFTS: 59

Ornithine Transcarbamylase Deficiency, Hyperammonemia Due to (OTCD)

Categories: Genetic diseases, Metabolic diseases, Neuronal diseases, Rare diseases
Genes Variations Tissues Related diseases Publications Pathways Symptoms & Phenotypes Drugs
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Aliases & Classifications for Ornithine Transcarbamylase Deficiency, Hyperammonemia Due to

About this section

MalaCards integrated aliases for Ornithine Transcarbamylase Deficiency, Hyperammonemia Due to:

Name: Ornithine Transcarbamylase Deficiency, Hyperammonemia Due to 56 37
Ornithine Carbamoyltransferase Deficiency 56 12 24 52 58 73 29 6 15 17 71
Ornithine Transcarbamylase Deficiency 56 12 24 52 25 58 73 36 13 54
Otc Deficiency 56 24 52 58 73
Ornithine Carbamoyltransferase Deficiency Disease 25 54 43
Otcd 52 73
Hyperammonemia Due to Ornithine Carbamoyltransferase Deficiency 73
Deficiency, Ornithine Carbamoyltransferase 39
Deficiency of Citrulline Phosphorylase 12
Oct Deficiency 58

Characteristics:

Orphanet epidemiological data:

58
ornithine transcarbamylase deficiency
Inheritance: X-linked recessive; Prevalence: 1-9/100000 (Europe),1-9/100000 (Italy),1-9/100000 (Australia),1-9/100000 (Finland),1-9/1000000 (Canada),1-9/100000 (United States),1-9/100000 (Worldwide); Age of onset: All ages,Neonatal; Age of death: any age,infantile;

OMIM:

56
Miscellaneous:
two types - lethal neonatal and less severe, late onset
clinical spectrum in males ranges from lethal neonatal onset to milder forms with first recognized episode in late childhood or even in adulthood
carrier females may present with postpartum hyperammonemia
some carrier females have episodes of significant hyperammonemia in infancy or childhood
prevalence of 1 in 40,000 to 1 in 80,000

Inheritance:
x-linked recessive


HPO:

31
ornithine transcarbamylase deficiency, hyperammonemia due to:
Inheritance x-linked recessive inheritance


GeneReviews:

24
Penetrance Penetrance for otc deficiency is complete in hemizygous males....

Classifications:

MalaCards categories:
Global: Genetic diseases Rare diseases Metabolic diseases
Anatomical: Neuronal diseases
See all MalaCards categories (disease lists)
ICD10: 32 33
Orphanet: 58  
Rare neurological diseases
Inborn errors of metabolism


External Ids:

Disease Ontology 12 DOID:9271
OMIM 56 311250
KEGG 36 H00187
NCIt 49 C84957
SNOMED-CT 67 80908008
ICD10 32 E72.4
MESH via Orphanet 44 D020163
ICD10 via Orphanet 33 E72.4
UMLS via Orphanet 72 C0268542
Orphanet 58 ORPHA664
UMLS 71 C0268542
Sources

Summaries for Ornithine Transcarbamylase Deficiency, Hyperammonemia Due to

About this section
Genetics Home Reference : 25 Ornithine transcarbamylase 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. Ornithine transcarbamylase deficiency can become evident at any age. The most severe form occurs in the first few days of life. This neonatal-onset form of the disorder usually affects males; it is very rare in females. An infant with the neonatal-onset form of ornithine transcarbamylase deficiency may be lacking in energy (lethargic) or unwilling to eat, and have a poorly-controlled breathing rate or body temperature. Infants with this disorder may be described as "floppy" and can experience seizures or coma. Complications from ornithine transcarbamylase deficiency may include developmental delay and intellectual disability. Progressive liver damage may also occur. In some affected individuals, signs and symptoms of ornithine transcarbamylase deficiency may be less severe, and may not appear until later in life. The late-onset form of the disorder occurs in both males and females. People with late-onset ornithine transcarbamylase deficiency may experience episodes of altered mental status, such as delirium, erratic behavior, or a reduced level of consciousness. Headaches, vomiting, aversion to protein foods, and seizures can also occur in this form of the disorder.

MalaCards based summary : Ornithine Transcarbamylase Deficiency, Hyperammonemia Due to, also known as ornithine carbamoyltransferase deficiency, is related to carbamoyl phosphate synthetase i deficiency, hyperammonemia due to and reye syndrome, and has symptoms including seizures, vomiting and lethargy. An important gene associated with Ornithine Transcarbamylase Deficiency, Hyperammonemia Due to is OTC (Ornithine Carbamoyltransferase), and among its related pathways/superpathways are Arginine biosynthesis and Metabolism. The drugs Phenylacetic acid and Clotrimazole have been mentioned in the context of this disorder. Affiliated tissues include Liver, testes and brain, and related phenotypes are splenomegaly and aminoaciduria

Disease Ontology : 12 An urea cycle disorder that involves a mutated and ineffective form of the enzyme ornithine transcarbamylase.

NIH Rare Diseases : 52 Ornithine transcarbamylase (OTC) deficiency is a genetic disease that causes too much ammonia to accumulate in the blood (hyperammonemia). Ammonia is toxic when levels are too high and especially affects the nervous system. Severe OTC deficiency (the early-onset form) typically affects males (and rarely females) and causes symptoms in the newborn period or early childhood. Signs and symptoms of this form may include lack of energy and appetite, poorly-controlled breathing rate and body temperature, unusual body movements, seizures , or coma. When not treated, the disease can lead to development delay, intellectual disability , and liver damage. Less frequently, symptoms of OTC deficiency begin later in life (the late-onset form) and are less severe. This form occurs in both males and females. Symptoms of this form may include episodes of delirium, erratic behavior, a reduced level of consciousness, headaches, vomiting, and seizures. OTC is caused by mutations in the OTC gene and inheritance is X-linked . Treatment involves removing protein from the diet, taking certain medications, and having hemodialysis if needed for extremely high blood ammonia levels.

OMIM : 56 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 triad of hyperammonemia, encephalopathy, and respiratory alkalosis. Five disorders involving different defects in the biosynthesis of the enzymes of the urea cycle have been described: OTC deficiency, carbamyl phosphate synthetase deficiency (237300), argininosuccinate synthetase deficiency, or citrullinemia (215700), argininosuccinate lyase deficiency (207900), and arginase deficiency (207800). (311250)

KEGG : 36 Ornithine transcarbamylase deficiency, the most common urea cycle defect, results in failure to thrive, hypotonia, seizures and mental retardation.

UniProtKB/Swiss-Prot : 73 Ornithine carbamoyltransferase deficiency: An X-linked disorder of the urea cycle which causes a form of hyperammonemia. Mutations with no residual enzyme activity are always expressed in hemizygote males by a very severe neonatal hyperammonemic coma that generally proves to be fatal. Heterozygous females are either asymptomatic or express orotic aciduria spontaneously or after protein intake. The disorder is treatable with supplemental dietary arginine and low protein diet. The arbitrary classification of patients into the 'neonatal' group (clinical hyperammonemia in the first few days of life) and 'late' onset (clinical presentation after the neonatal period) has been used to differentiate severe from mild forms.

Wikipedia : 74 Ornithine transcarbamylase deficiency is the most common urea cycle disorder in humans. It is an... more...

GeneReviews: NBK154378
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Related Diseases for Ornithine Transcarbamylase Deficiency, Hyperammonemia Due to

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Diseases related to Ornithine Transcarbamylase Deficiency, Hyperammonemia Due to via text searches within MalaCards or GeneCards Suite gene sharing:

(show top 50) (show all 133)
# Related Disease Score Top Affiliating Genes
1 carbamoyl phosphate synthetase i deficiency, hyperammonemia due to 31.7 SLC25A15 OTC NAGS CPS1 ASS1 ASL
2 reye syndrome 30.7 OTC ASS1
3 carbonic anhydrase va deficiency, hyperammonemia due to 30.2 SLC25A15 SLC25A13 OTC NAGS CPS1 ASS1
4 orotic aciduria 30.1 OTC NAGS DPYD CPS1 ASS1 ASL
5 argininemia 29.4 SLC25A15 SLC25A13 OTC NAGS CPS1 ASS1
6 hyperornithinemia-hyperammonemia-homocitrullinuria syndrome 29.0 SLC25A15 SLC25A13 OTC NAGS CPS1 ASS1
7 urea cycle disorder 28.8 SLC25A15 SLC25A13 OTC NAGS MMD CPS1
8 argininosuccinic aciduria 28.7 SLC25A15 SLC25A13 OTC NAGS MMD CPS1
9 propionic acidemia 28.4 OTC NAGS MMD CPS1 BCKDHB ASS1
10 citrullinemia, classic 27.5 SLC25A15 SLC25A13 OTC NAGS MMD CPS1
11 brain edema 10.6
12 ataxia and polyneuropathy, adult-onset 10.6
13 liver disease 10.5
14 encephalopathy 10.5
15 hepatocellular carcinoma 10.4
16 hepatic encephalopathy 10.4
17 subacute delirium 10.4
18 postpartum psychosis 10.4 OTC ASS1
19 ocular motor apraxia 10.3
20 inherited metabolic disorder 10.3
21 acyl-coa dehydrogenase deficiency 10.3 OTC ASS1
22 migraine with or without aura 1 10.3
23 acrodermatitis enteropathica, zinc-deficiency type 10.3
24 stroke, ischemic 10.3
25 abdominal obesity-metabolic syndrome 1 10.3
26 hemiplegia 10.3
27 disseminated intravascular coagulation 10.3
28 hepatic coma 10.3
29 cerebral palsy 10.3
30 acrodermatitis 10.3
31 bilirubin metabolic disorder 10.3
32 chronic granulomatous disease 10.3
33 lactic acidosis 10.3
34 fibrolamellar carcinoma 10.3
35 enteropathica 10.3
36 tremor 10.3
37 purine-pyrimidine metabolic disorder 10.2 TMSB15A DPYD
38 3-methylcrotonyl-coa carboxylase deficiency 10.2 SLC25A13 MMD
39 attention deficit-hyperactivity disorder 10.2
40 alkaptonuria 10.2
41 rett syndrome 10.2
42 chorea, childhood-onset, with psychomotor retardation 10.2
43 global developmental delay, absent or hypoplastic corpus callosum, and dysmorphic facies 10.2
44 choreatic disease 10.2
45 facial paralysis 10.2
46 hyperinsulinism 10.2
47 hepatitis 10.2
48 transient cerebral ischemia 10.2
49 acute pancreatitis 10.2
50 pancreatitis 10.2

Graphical network of the top 20 diseases related to Ornithine Transcarbamylase Deficiency, Hyperammonemia Due to:



Diseases related to Ornithine Transcarbamylase Deficiency, Hyperammonemia Due to
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Symptoms & Phenotypes for Ornithine Transcarbamylase Deficiency, Hyperammonemia Due to

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Human phenotypes related to Ornithine Transcarbamylase Deficiency, Hyperammonemia Due to:

58 31 (show all 23)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 splenomegaly 58 31 hallmark (90%) Very frequent (99-80%) HP:0001744
2 aminoaciduria 58 31 hallmark (90%) Very frequent (99-80%) HP:0003355
3 hypoglycemia 58 31 hallmark (90%) Very frequent (99-80%) HP:0001943
4 hepatic failure 58 31 hallmark (90%) Very frequent (99-80%) HP:0001399
5 hyperammonemia 58 31 hallmark (90%) Very frequent (99-80%) HP:0001987
6 pyloric stenosis 58 31 hallmark (90%) Very frequent (99-80%) HP:0002021
7 stroke 31 occasional (7.5%) HP:0001297
8 intellectual disability 31 HP:0001249
9 global developmental delay 31 HP:0001263
10 failure to thrive 31 HP:0001508
11 vomiting 31 HP:0002013
12 irritability 31 HP:0000737
13 ataxia 31 HP:0001251
14 lethargy 31 HP:0001254
15 hyperglutaminemia 31 HP:0003217
16 episodic ammonia intoxication 31 HP:0001951
17 coma 31 HP:0001259
18 episodic ataxia 31 HP:0002131
19 cerebral edema 31 HP:0002181
20 protein avoidance 31 HP:0002038
21 respiratory alkalosis 31 HP:0001950
22 low plasma citrulline 31 HP:0003572
23 seizure 31 HP:0001250

Symptoms via clinical synopsis from OMIM:

56
Neurologic Central Nervous System:
seizures
lethargy
coma
episodic ataxia
cerebral edema
more
Abdomen Gastrointestinal:
vomiting
protein avoidance

Laboratory Abnormalities:
hyperammonemia
low plasma citrulline
high plasma glutamine
low plasma arginine
high plasma asparagine
more
Growth Other:
failure to thrive

Neurologic Behavioral Psychiatric Manifestations:
irritability

Metabolic Features:
episodic ammonia intoxication
respiratory alkalosis

Clinical features from OMIM:

311250

UMLS symptoms related to Ornithine Transcarbamylase Deficiency, Hyperammonemia Due to:


seizures, vomiting, lethargy
Sources

Drugs & Therapeutics for Ornithine Transcarbamylase Deficiency, Hyperammonemia Due to

About this section

Drugs for Ornithine Transcarbamylase Deficiency, Hyperammonemia Due to (from DrugBank, HMDB, Dgidb, PharmGKB, IUPHAR, NovoSeek, BitterDB):

(show all 27)
# Name Status Phase Clinical Trials Cas Number PubChem Id
1
Phenylacetic acid Approved Phase 2 103-82-2 999
2
Clotrimazole Approved, Vet_approved Phase 2 23593-75-1 2812
3
Miconazole Approved, Investigational, Vet_approved Phase 2 22916-47-8 4189
4
Prednisolone phosphate Approved, Vet_approved Phase 1, Phase 2 302-25-0
5
Methylprednisolone Approved, Vet_approved Phase 1, Phase 2 83-43-2 6741
6
Prednisone Approved, Vet_approved Phase 1, Phase 2 53-03-2 5865
7
Methylprednisolone hemisuccinate Approved Phase 1, Phase 2 2921-57-5
8
Prednisolone Approved, Vet_approved Phase 1, Phase 2 50-24-8 5755
9 Prednisolone acetate Approved, Vet_approved Phase 1, Phase 2 52-21-1
10
carbamide peroxide Approved Phase 1, Phase 2 124-43-6
11
Acetohydroxamic acid Approved Phase 1, Phase 2 546-88-3 1990
12
Glutamic acid Approved, Nutraceutical Phase 2 56-86-0 33032
13
Prednisolone hemisuccinate Experimental Phase 1, Phase 2 2920-86-7
14 Anti-Infective Agents Phase 2
15 4-phenylbutyric acid Phase 2
16 Antifungal Agents Phase 2
17 Sodium Benzoate Phase 2
18 Antimetabolites Phase 2
19 glutamine Phase 2
20 Methylprednisolone Acetate Phase 1, Phase 2
21 Antineoplastic Agents, Hormonal Phase 1, Phase 2
22 Hormone Antagonists Phase 1, Phase 2
23 glucocorticoids Phase 1, Phase 2
24 Anti-Inflammatory Agents Phase 1, Phase 2
25 Liver Extracts Phase 1
26
Valproic acid Approved, Investigational 99-66-1 3121
27 Vaccines

Interventional clinical trials:

(show all 28)
# Name Status NCT ID Phase Drugs
1 N-Carbamylglutamate (Carbaglu) In The Treatment Of Hyperammonemia Active, not recruiting NCT00843921 Phase 2, Phase 3 N-carbamylglutamate
2 Open, Prospective, Uncontrolled, Multicentre Study to Evaluate The Safety and Efficacy of Multiple Applications of Liver Cell Suspension Into The Portal Vein in Children With Urea Cycle Disorders (UCDs) Completed NCT00718627 Phase 2
3 Phase II Study of Sodium Phenylbutyrate, Sodium Benzoate, Sodium Phenylacetate, and Dietary Intervention for Urea Cycle Disorders Completed NCT00004767 Phase 2 Sodium Benzoate;Sodium Phenylacetate;Sodium Phenylbutyrate
4 Hypothermia Treatment in Hyperammonemia and Encephalopathy Completed NCT01624311 Phase 2
5 A Phase 2, Open-label Study to Evaluate the Efficacy and Safety of KB195 in Subjects With A Urea Cycle Disorder With Inadequate Control on Standard of Care Recruiting NCT03933410 Phase 2 KB195
6 A Phase 1/2, Open-Label Safety and Dose-Finding Study of Adeno-Associated Virus (AAV) Serotype 8 (AAV8)-Mediated Gene Transfer of Human Ornithine Transcarbamylase (OTC) in Adults With Late-Onset OTC Deficiency Active, not recruiting NCT02991144 Phase 1, Phase 2 Oral prednisone
7 Short-Term Outcome of N-Carbamylglutamate in the Treatment of Acute Hyperammonemia Active, not recruiting NCT01599286 Phase 2 Carbaglu;Placebo;Standard of Care Treatment
8 Manipulating the Gut Microbiome Study Terminated NCT03181828 Phase 1, Phase 2 Acetohydroxamic Acid Oral Tablet [Lithostat]
9 A Phase 1/2 Single Ascending Dose Study Evaluating the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Intravenously Administered MRT5201 in Subjects With Ornithine Transcarbamylase Deficiency Withdrawn NCT03767270 Phase 1, Phase 2
10 Increasing Ureagenesis in Inborn Errors of Metabolism With N-Carbamylglutamate Withdrawn NCT01341379 Phase 2 N-carbamylglutamate
11 Therapeutic and Metabolic Studies of Urea Cycle Disorders: Part A: Nitrogen Flux and Ureagenesis; Part B (Closed): Phase I Adenovirus Vector-Mediated Gene Therapy for Ornithine Transcarbamylase Deficiency Unknown status NCT00004307 Phase 1
12 A Phase 1 Randomized, Double Blinded, Placebo Controlled, Ascending Dose Study to Assess the Safety, Tolerability, and Pharmacokinetics of Single Doses of ARCT-810 in Healthy Adult Subjects Recruiting NCT04416126 Phase 1
13 A Phase 1b Randomized, Double Blinded, Placebo Controlled, Ascending Dose Study to Assess the Safety, Tolerability, and Pharmacokinetics of Single Doses of ARCT-810 in Clinically Stable Patients With Ornithine Transcarbamylase Deficiency Not yet recruiting NCT04442347 Phase 1
14 Hepatocyte Transplantation for Liver Based Metabolic Disorders Suspended NCT01345578 Phase 1 human hepatocyte transplantation
15 Phase I Study of Adenoviral Vector Mediated Gene Transfer for Ornithine Transcarbamylase in Adults With Partial Ornithine Transcarbamylase Deficiency Terminated NCT00004498 Phase 1
16 Phase I Pilot Study of Liver-Directed Gene Therapy for Partial Ornithine Transcarbamylase Deficiency Terminated NCT00004386 Phase 1
17 Investigation of Brain Nitrogen in Partial Ornithine Transcarbamylase Deficiency (OTCD) Using 1 H MRS, DTI, and fMRI Completed NCT01569568
18 Assessing Neural Mechanisms of Injury in Inborn Errors of Urea Metabolism Using Structural MRI, Functional MRI, and Magnetic Resonance Spectroscopy Completed NCT00472732
19 A Single-Center Study to Assess Plasma Ammonia Time-Normalized Area Under the Curve From Time Zero to 24 Hours and Rate of Ureagenesis in Healthy Adult Subjects Completed NCT04269122
20 Valproic Acid-associated Hypoalbuminemia in Medically Fragile Pediatric and Young Adult Patients in a Long Term Care Facility Part 1: Potential Mechanism for Decreased Albumin Synthesis Completed NCT00723762
21 Open, Prospective, Diagnostic, Multicentre Study in Healthy Subjects, Patients With Urea Cycle Disorders (UCD), and Carriers of UCD Mutations, to Evaluate in Vivo Ureagenesis Measured After a Single Application of Sodium [1,2-13C]-Acetate Completed NCT01549015
22 Neuroimaging and Neuropsychological Outcomes in Urea Cycle Disorders Recruiting NCT02935283
23 Identification and Validation of Relevant Patient and Observer Reported Outcome Measurements in Inborn Errors of Metabolism Recruiting NCT04248062
24 Longitudinal Study of Urea Cycle Disorders Recruiting NCT00237315
25 Prospective Cross-Sectional Non-invasive Assessment of Chronic Liver Disease in Urea Cycle Disorders Recruiting NCT03721367
26 A Long-Term Follow-up Study to Evaluate Safety and Efficacy of Adeno-Associated Virus (AAV) Serotype 8 (AAV8)-Mediated Gene Transfer of Human Ornithine Transcarbamylase (OTC) in Adults With Late-Onset OTC Deficiency Enrolling by invitation NCT03636438
27 The NIH UNI Study: Urea Cycle Disorders, Nutrition and Immunity Terminated NCT01421888
28 Multimodal Neuroimaging and Neurocognitive Assessment of Biomarkers and Response to Sapropterin Dihydrochloride Treatment in Phenylketonuria Withdrawn NCT01412437 sapropterin dihydrochloride;sapropterin dihydrochloride

Search NIH Clinical Center for Ornithine Transcarbamylase Deficiency, Hyperammonemia Due to

Cell-based therapeutics:


LifeMap Discovery
Data from LifeMap, the Embryonic Development and Stem Cells Database
Read about Ornithine Transcarbamylase Deficiency, Hyperammonemia Due to cell therapies at LifeMap Discovery.
Stem-cell-based therapeutic approaches for Ornithine Transcarbamylase Deficiency, Hyperammonemia Due to:
Hepatocyte transplantation for treatment of liver disorders
Promethera HepaStem, human adult liver progenitor cells for liver diseases
Embryonic/Adult Cultured Cells Related to Ornithine Transcarbamylase Deficiency, Hyperammonemia Due to:
Hepatocytes PMIDs: 12777539 22167636 22789058 9580649 15239608
Adult liver progenitor cells PMIDs: 22525602 23211283 24142276 22900053 19091822

Cochrane evidence based reviews: ornithine carbamoyltransferase deficiency disease

Sources

Genetic Tests for Ornithine Transcarbamylase Deficiency, Hyperammonemia Due to

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Genetic tests related to Ornithine Transcarbamylase Deficiency, Hyperammonemia Due to:

# Genetic test Affiliating Genes
1 Ornithine Carbamoyltransferase Deficiency 29 OTC
Sources

Anatomical Context for Ornithine Transcarbamylase Deficiency, Hyperammonemia Due to

About this section

MalaCards organs/tissues related to Ornithine Transcarbamylase Deficiency, Hyperammonemia Due to:

40
Liver, Testes, Brain, Fetal Liver, Retina
LifeMap Discovery
Data from LifeMap, the Embryonic Development and Stem Cells Database

Cells/anatomical compartments in embryo or adult related to Ornithine Transcarbamylase Deficiency, Hyperammonemia Due to:
# Tissue Anatomical CompartmentCell Relevance
1 Liver Liver Lobule Hepatocytes Potential therapeutic candidate
Sources

Publications for Ornithine Transcarbamylase Deficiency, Hyperammonemia Due to

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Articles related to Ornithine Transcarbamylase Deficiency, Hyperammonemia Due to:

(show top 50) (show all 315)
# Title Authors PMID Year
1
Maternal gonadal mosaicism causing ornithine transcarbamylase deficiency. 56 24 6
10405441 1999
2
Mutations and polymorphisms in the human ornithine transcarbamylase gene. 6 56
8364586 1993
3
Heterozygote ornithine transcarbamylase deficiency presenting as symptomatic hyperammonemia during initiation of valproate therapy. 56 24 54
1549234 1992
4
Retrospective survey of urea cycle disorders: Part 1. Clinical and laboratory observations of thirty-two Japanese male patients with ornithine transcarbamylase deficiency. 24 56 54
2012137 1991
5
Characterization of point mutations in the same arginine codon in three unrelated patients with ornithine transcarbamylase deficiency. 56 6
3170748 1988
6
Mosaicism for an intragenic deletion in a boy with mild ornithine transcarbamylase deficiency. 6 56
2843770 1988
7
A longitudinal study of urea cycle disorders. 56 24
25135652 2014
8
Mutations and polymorphisms in the human ornithine transcarbamylase gene. 24 6
11793468 2002
9
Plasma glutamine and ammonia concentrations in ornithine carbamoyltransferase deficiency and citrullinaemia. 56 54 61
11804205 2001
10
Genotype spectrum of ornithine transcarbamylase deficiency: correlation with the clinical and biochemical phenotype. 56 24
10946359 2000
11
X-inactivation pattern in the liver of a manifesting female with ornithine transcarbamylase (OTC) deficiency. 24 56
9831349 1998
12
Allopurinol-induced orotidinuria. A test for mutations at the ornithine carbamoyltransferase locus in women. 54 61 56
2342523 1990
13
Hyperammonemia in women with a mutation at the ornithine carbamoyltransferase locus. A cause of postpartum coma. 24 56
2342525 1990
14
Natural history of symptomatic partial ornithine transcarbamylase deficiency. 56 24
3945292 1986
15
X-chromosome inactivation in human liver: confirmation of X-linkage of ornithine transcarbamylase. 56 24
941900 1976
16
Disruption of OTC promoter-enhancer interaction in a patient with symptoms of ornithine carbamoyltransferase deficiency. 61 54 24
20127982 2010
17
Ornithine transcarbamylase deficiency and pancreatitis. 56 54
11148526 2001
18
Ornithine transcarbamylase deficiency: ten new mutations and high proportion of de novo mutations in heterozygous females. 6 54
9143919 1997
19
In vivo nitrogen metabolism in ornithine transcarbamylase deficiency. 54 56
8903337 1996
20
Long-term treatment of girls with ornithine transcarbamylase deficiency. 54 56
8778603 1996
21
Prospective treatment of urea cycle disorders. 56 54
1720458 1991
22
Sporadic late onset ornithine transcarbamylase deficiency in a boy with somatic mosaicism for an intragenic deletion. 6 54
2208768 1990
23
Carrier detection in a partially dominant X-linked disease: ornithine transcarbamylase deficiency. 56 54
2298453 1990
24
Valproate toxicity and ornithine carbamoyltransferase deficiency. 56 61
2878165 1986
25
Prenatal treatment of ornithine transcarbamylase deficiency. 56
29396029 2018
26
Recommendations for reporting of secondary findings in clinical exome and genome sequencing, 2016 update (ACMG SF v2.0): a policy statement of the American College of Medical Genetics and Genomics. 6
27854360 2017
27
Ornithine Transcarbamylase Deficiency 6
24006547 2013
28
Inherited metabolic disorders and stroke part 2: homocystinuria, organic acidurias, and urea cycle disorders. 56
20142522 2010
29
Fatal initial adult-onset presentation of urea cycle defect. 56
18071043 2007
30
Ornithine transcarbamylase deficiency presenting as encephalopathy during adulthood following bariatric surgery. 24 54
17210820 2007
31
Biochemical data in ornithine transcarbamylase deficiency (OTCD) carrier risk estimation: logistic discrimination and combination with genetic information. 24 54
16453063 2006
32
Effect of alternative pathway therapy on branched chain amino acid metabolism in urea cycle disorder patients. 54 24
15050979 2004
33
Metabolic and neuropsychological phenotype in women heterozygous for ornithine transcarbamylase deficiency. 54 24
14705115 2004
34
Urea Cycle Disorders Overview 6
20301396 2003
35
A case of acrodermatitis enteropathica-like dermatosis caused by ornithine transcarbamylase deficiency. 56
12063505 2002
36
Inborn errors of metabolism in the Italian pediatric population: a national retrospective survey. 54 24
11953730 2002
37
The clinically variable R40H mutant ornithine carbamoyltransferase shows cytosolic degradation of the precursor protein in CHO cells. 6
11768581 2001
38
Late-onset ornithine transcarbamylase deficiency in two families with different mutations in the same codon. 6
11260212 2001
39
Hyperammonaemic encephalopathy after initiation of valproate therapy in unrecognised ornithine transcarbamylase deficiency. 54 24
9598692 1998
40
Familial lethal inheritance of a mutated paternal gene in females causing X-linked ornithine transcarbamylase (OTC) deficiency. 6
9056557 1997
41
Clinical and biochemical heterogeneity in females of a large pedigree with ornithine transcarbamylase deficiency due to the R141Q mutation. 54 24
8985493 1996
42
Phenotypic variability in male patients carrying the mutant ornithine transcarbamylase (OTC) allele, Arg40His, ranging from a child with an unfavourable prognosis to an asymptomatic older adult. 6
8863155 1996
43
Relative frequency of mutations causing ornithine transcarbamylase deficiency in 78 families. 56
8786061 1996
44
Patient selection may affect gene therapy success. Dominant negative effects observed for ornithine transcarbamylase in mouse and human hepatocytes. 56
8609240 1996
45
Demonstration of the spf-ash mutation in Spanish patients with ornithine transcarbamylase deficiency of moderate severity. 6
7860064 1995
46
Site specific screening for point mutations in ornithine transcarbamylase deficiency. 6
1353535 1992
47
Screening for gene deletions and known mutations in 13 patients with ornithine transcarbamylase deficiency. 6
1627356 1992
48
Fatal hyperammonemia resulting from a C-to-T mutation at a MspI site of the ornithine transcarbamylase gene. 6
1721894 1991
49
Arginine 109 to glutamine mutation in a girl with ornithine carbamoyl transferase deficiency. 6
1757964 1991
50
Identification of RNA splicing errors resulting in human ornithine transcarbamylase deficiency. 6
2035531 1991
Sources

Variations for Ornithine Transcarbamylase Deficiency, Hyperammonemia Due to

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ClinVar genetic disease variations for Ornithine Transcarbamylase Deficiency, Hyperammonemia Due to:

6 (show top 50) (show all 139) ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎
# Gene Name Type Significance ClinVarId dbSNP ID GRCh37 Pos GRCh38 Pos
1 OTC NM_000531.6(OTC):c.517C>G (p.Leu173Val)SNV Pathogenic 430717 rs1131692152 X:38260658-38260658 X:38401405-38401405
2 OTC NM_000531.6(OTC):c.298+2T>GSNV Pathogenic 451770 rs1555972538 X:38229132-38229132 X:38369879-38369879
3 OTC NM_000531.6(OTC):c.540+265G>ASNV Pathogenic 449382 rs1555975756 X:38260946-38260946 X:38401693-38401693
4 OTC NC_000023.11:g.(?_38401255)_(38401693_?)deldeletion Pathogenic 584165 X:38260508-38260946 X:38401255-38401693
5 OTC NM_000531.6(OTC):c.387-1G>ASNV Pathogenic 803976 X:38260527-38260527 X:38401274-38401274
6 OTC NC_000023.11:g.(?_38381322)_(38413090_?)deldeletion Pathogenic 583414 X:38240575-38272343 X:38381322-38413090
7 subset of 33 genes: BCOR , CYBB , DMD , GK , NR0B1 , OTC , TSPAN7 , USP9X NC_000023.10:g.(?_30326313)_(41000684_?)deldeletion Pathogenic 833473 X:30326313-41000684
8 OTC NC_000023.11:g.(?_38352331)_(38352793_?)deldeletion Pathogenic 830543 X:38211584-38212046
9 OTC NM_000531.6(OTC):c.652G>C (p.Ala218Pro)SNV Pathogenic 870314 X:38262982-38262982 X:38403729-38403729
10 OTC NM_000531.6(OTC):c.635G>T (p.Gly212Val)SNV Pathogenic 870315 X:38262965-38262965 X:38403712-38403712
11 OTC NM_000531.6(OTC):c.584G>C (p.Gly195Ala)SNV Pathogenic 870316 X:38262914-38262914 X:38403661-38403661
12 OTC NM_000531.6(OTC):c.488T>G (p.Leu163Arg)SNV Pathogenic 870317 X:38260629-38260629 X:38401376-38401376
13 OTC NM_000531.6(OTC):c.473C>T (p.Pro158Leu)SNV Pathogenic 870322 X:38260614-38260614 X:38401361-38401361
14 OTC NM_000531.6(OTC):c.298G>T (p.Gly100Cys)SNV Pathogenic 870323 X:38229130-38229130 X:38369877-38369877
15 OTC NM_000531.6(OTC):c.214G>A (p.Glu72Lys)SNV Pathogenic 870324 X:38226680-38226680 X:38367427-38367427
16 OTC NM_000531.6(OTC):c.77+5G>CSNV Pathogenic 870325 X:38212031-38212031 X:38352778-38352778
17 OTC NM_000531.6(OTC):c.766G>T (p.Gly256Ter)SNV Pathogenic 870326 X:38268177-38268177 X:38408924-38408924
18 OTC NM_000531.6(OTC):c.327T>A (p.Cys109Ter)SNV Pathogenic 870327 X:38240623-38240623 X:38381370-38381370
19 OTC NM_000531.6(OTC):c.568dup (p.Thr190fs)duplication Pathogenic 870328 X:38262897-38262898 X:38403644-38403645
20 OTC NM_000531.6(OTC):c.740C>G (p.Thr247Arg)SNV Pathogenic 870329 X:38268151-38268151 X:38408898-38408898
21 OTC NM_000531.6(OTC):c.944T>C (p.Val315Ala)SNV Pathogenic 870330 X:38271191-38271191 X:38411938-38411938
22 OTC NM_000531.6(OTC):c.946T>G (p.Phe316Val)SNV Pathogenic 870331 X:38271193-38271193 X:38411940-38411940
23 OTC NM_000531.6(OTC):c.1009G>T (p.Val337Phe)SNV Pathogenic 870332 X:38280279-38280279 X:38421026-38421026
24 OTC NM_000531.6(OTC):c.1015G>A (p.Val339Met)SNV Pathogenic 870333 X:38280285-38280285 X:38421032-38421032
25 OTC NC_000023.11:g.38369877deldeletion Pathogenic 870610
26 OTC NM_000531.6(OTC):c.1052del (p.Lys351fs)deletion Pathogenic 915468 X:38280321-38280321 X:38421068-38421068
27 OTC NM_000531.6(OTC):c.116G>C (p.Gly39Ala)SNV Pathogenic 915469 X:38226582-38226582 X:38367329-38367329
28 OTC NM_000531.6(OTC):c.217-2A>GSNV Pathogenic 915470 X:38229047-38229047 X:38369794-38369794
29 OTC OTC, DELdeletion Pathogenic 10986
30 OTC NM_000531.6(OTC):c.422G>A (p.Arg141Gln)SNV Pathogenic 10987 rs68026851 X:38260563-38260563 X:38401310-38401310
31 OTC NM_000531.6(OTC):c.421C>T (p.Arg141Ter)SNV Pathogenic 10988 rs67960011 X:38260562-38260562 X:38401309-38401309
32 OTC NM_000531.6(OTC):c.332T>C (p.Leu111Pro)SNV Pathogenic 10989 rs1800324 X:38240628-38240628 X:38381375-38381375
33 OTC NM_000531.6(OTC):c.646C>G (p.Gln216Glu)SNV Pathogenic 10990 rs72558423 X:38262976-38262976 X:38403723-38403723
34 OTC NM_000531.6(OTC):c.460G>T (p.Glu154Ter)SNV Pathogenic 10991 rs72556267 X:38260601-38260601 X:38401348-38401348
35 OTC NM_000531.6(OTC):c.134T>C (p.Leu45Pro)SNV Pathogenic 10992 rs72554312 X:38226600-38226600 X:38367347-38367347
36 OTC NM_000531.6(OTC):c.77G>A (p.Arg26Gln)SNV Pathogenic 10993 rs68031618 X:38212026-38212026 X:38352773-38352773
37 OTC NM_000531.6(OTC):c.717+2T>CSNV Pathogenic 10996 rs72558431 X:38268050-38268050 X:38408797-38408797
38 OTC NM_000531.6(OTC):c.387-2A>TSNV Pathogenic 10998 rs66556380 X:38260526-38260526 X:38401273-38401273
39 OTC NM_000531.6(OTC):c.829C>T (p.Arg277Trp)SNV Pathogenic 10999 rs72558454 X:38268240-38268240 X:38408987-38408987
40 OTC NM_000531.6(OTC):c.674C>T (p.Pro225Leu)SNV Pathogenic 11000 rs67120076 X:38268005-38268005 X:38408752-38408752
41 OTC NM_000531.6(OTC):c.259G>A (p.Glu87Lys)SNV Pathogenic 11001 rs72554338 X:38229091-38229091 X:38369838-38369838
42 OTC NM_000531.6(OTC):c.148G>T (p.Gly50Ter)SNV Pathogenic 11002 rs67486158 X:38226614-38226614 X:38367361-38367361
43 OTC NM_000531.6(OTC):c.484G>A (p.Gly162Arg)SNV Pathogenic 11003 rs66626662 X:38260625-38260625 X:38401372-38401372
44 OTC NM_000531.6(OTC):c.236G>A (p.Gly79Glu)SNV Pathogenic 11006 rs72554331 X:38229068-38229068 X:38369815-38369815
45 OTC NM_000531.6(OTC):c.281G>C (p.Arg94Thr)SNV Pathogenic 11007 rs72554345 X:38229113-38229113 X:38369860-38369860
46 OTC NM_000531.6(OTC):c.1033T>G (p.Tyr345Asp)SNV Pathogenic 11009 rs66469337 X:38280303-38280303 X:38421050-38421050
47 OTC NM_000531.6(OTC):c.386G>A (p.Arg129His)SNV Pathogenic 11010 rs66656800 X:38240682-38240682 X:38381429-38381429
48 OTC NM_000531.6(OTC):c.444G>C (p.Leu148Phe)SNV Pathogenic 11011 rs66741318 X:38260585-38260585 X:38401332-38401332
49 OTC NM_000531.6(OTC):c.617T>G (p.Met206Arg)SNV Pathogenic 11012 rs72558412 X:38262947-38262947 X:38403694-38403694
50 OTC NC_000023.11:g.(?_38367271)_(38367449_?)deldeletion Pathogenic 831937 X:38226524-38226702

UniProtKB/Swiss-Prot genetic disease variations for Ornithine Transcarbamylase Deficiency, Hyperammonemia Due to:

73 (show top 50) (show all 111)
# Symbol AA change Variation ID SNP ID
1 OTC p.Arg26Gln VAR_004843 rs68031618
2 OTC p.Gly39Cys VAR_004844 rs72554306
3 OTC p.Arg40Cys VAR_004845 rs72554307
4 OTC p.Arg40His VAR_004846 rs72554308
5 OTC p.Thr44Ile VAR_004848 rs72554310
6 OTC p.Leu45Pro VAR_004849 rs72554312
7 OTC p.Leu45Val VAR_004850 rs72554311
8 OTC p.Asn47Ile VAR_004852 rs67939655
9 OTC p.Gly50Arg VAR_004853 rs67486158
10 OTC p.Tyr55Asp VAR_004854 rs72554319
11 OTC p.Met56Thr VAR_004855 rs72554320
12 OTC p.Ser60Leu VAR_004856 rs72554323
13 OTC p.Leu63Pro VAR_004857 rs72554324
14 OTC p.Gly79Glu VAR_004858 rs72554331
15 OTC p.Gly83Asp VAR_004860 rs72554337
16 OTC p.Gly83Arg VAR_004861 rs72554336
17 OTC p.Glu87Lys VAR_004862 rs72554338
18 OTC p.Lys88Asn VAR_004863 rs72554339
19 OTC p.Ser90Arg VAR_004864 rs72554342
20 OTC p.Arg92Gln VAR_004865 rs66550389
21 OTC p.Thr93Ala VAR_004866 rs72554344
22 OTC p.Arg94Thr VAR_004867 rs72554345
23 OTC p.Gly100Asp VAR_004868 rs72554349
24 OTC p.Ala102Glu VAR_004870 rs72554350
25 OTC p.His117Leu VAR_004872 rs66539573
26 OTC p.His117Arg VAR_004873 rs66539573
27 OTC p.Thr125Met VAR_004874 rs72554356
28 OTC p.Asp126Gly VAR_004875 rs72554358
29 OTC p.Arg129His VAR_004876 rs66656800
30 OTC p.Leu139Ser VAR_004877 rs72556259
31 OTC p.Arg141Pro VAR_004878 rs68026851
32 OTC p.Arg141Gln VAR_004879 rs68026851
33 OTC p.Leu148Phe VAR_004880 rs66741318
34 OTC p.Ile159Thr VAR_004881 rs72556269
35 OTC p.Asn161Ser VAR_004882 rs72556271
36 OTC p.Gly162Arg VAR_004883 rs66626662
37 OTC p.His168Gln VAR_004884 rs72556276
38 OTC p.His168Arg VAR_004885 rs66867430
39 OTC p.Ile172Met VAR_004886 rs72556280
40 OTC p.Ala174Pro VAR_004887 rs72556281
41 OTC p.Asp175Val VAR_004888 rs68033093
42 OTC p.Tyr176Cys VAR_004889 rs72556283
43 OTC p.Thr178Met VAR_004890 rs72556284
44 OTC p.Gln180His VAR_004892 rs72556287
45 OTC p.Glu181Gly VAR_004893 rs72556290
46 OTC p.His182Leu VAR_004894 rs72556291
47 OTC p.Tyr183Cys VAR_004895 rs72556293
48 OTC p.Tyr183Asp VAR_004896 rs72556292
49 OTC p.Gly188Arg VAR_004897 rs72556294
50 OTC p.Ser192Arg VAR_004898 rs72556298

Copy number variations for Ornithine Transcarbamylase Deficiency, Hyperammonemia Due to from CNVD:

7
# CNVD ID Chromosome Start End Type Gene Symbol CNVD Disease
1 262149 X 31500000 37500000 Copy number OTC Ornithine transcarbamylase deficiency
Sources

Expression for Ornithine Transcarbamylase Deficiency, Hyperammonemia Due to

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Search GEO for disease gene expression data for Ornithine Transcarbamylase Deficiency, Hyperammonemia Due to.
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Pathways for Ornithine Transcarbamylase Deficiency, Hyperammonemia Due to

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Pathways related to Ornithine Transcarbamylase Deficiency, Hyperammonemia Due to according to KEGG:

36
# Name Kegg Source Accession
1 Arginine biosynthesis hsa00220

Pathways related to Ornithine Transcarbamylase Deficiency, Hyperammonemia Due to according to GeneCards Suite gene sharing:

# Super pathways Score Top Affiliating Genes
1
Metabolism 65
Show member pathways
 13.71 SLC25A15 SLC25A13 OTC NDUFAF5 NAGS DPYD
2
Carbon metabolism 36
Show member pathways
 11.88 OTC NAGS CPS1 ASS1 ASL
3
Amino Acid metabolism 1
11.5 OTC CPS1 ASS1
4
Alanine, aspartate and glutamate metabolism 36
10.99 CPS1 ASS1 ASL
5
Arginine biosynthesis 36
Show member pathways
 10.77 OTC NAGS CPS1 ASS1 ASL
6
Alanine and aspartate metabolism 1
Show member pathways
 10.52 ASS1 ASL
7
Urea cycle and metabolism of amino groups 1
Show member pathways
 10.4 OTC NAGS CPS1 ASS1 ASL
Sources

GO Terms for Ornithine Transcarbamylase Deficiency, Hyperammonemia Due to

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Cellular components related to Ornithine Transcarbamylase Deficiency, Hyperammonemia Due to according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 mitochondrial matrix GO:0005759 9.46 OTC NAGS CPS1 BCKDHB
2 mitochondrial inner membrane GO:0005743 9.35 SLC25A15 SLC25A13 OTC NDUFAF5 CPS1
3 mitochondrion GO:0005739 9.23 SLC25A15 SLC25A13 OTC NDUFAF5 NAGS CPS1

Biological processes related to Ornithine Transcarbamylase Deficiency, Hyperammonemia Due to according to GeneCards Suite gene sharing:

(show all 15)
# Name GO ID Score Top Affiliating Genes
1 liver development GO:0001889 9.65 OTC CPS1 ASS1
2 cellular amino acid biosynthetic process GO:0008652 9.63 OTC ASS1 ASL
3 response to amino acid GO:0043200 9.55 CPS1 ASS1
4 response to steroid hormone GO:0048545 9.54 CPS1 ASS1
5 cellular response to glucagon stimulus GO:0071377 9.52 CPS1 ASS1
6 response to growth hormone GO:0060416 9.51 CPS1 ASS1
7 response to zinc ion GO:0010043 9.5 OTC CPS1 ASS1
8 response to amine GO:0014075 9.49 CPS1 ASS1
9 citrulline biosynthetic process GO:0019240 9.43 OTC CPS1
10 cellular response to oleic acid GO:0071400 9.4 CPS1 ASS1
11 arginine biosynthetic process via ornithine GO:0042450 9.37 OTC ASL
12 midgut development GO:0007494 9.33 OTC CPS1 ASS1
13 anion homeostasis GO:0055081 9.26 OTC CPS1
14 arginine biosynthetic process GO:0006526 9.26 OTC NAGS ASS1 ASL
15 urea cycle GO:0000050 9.1 SLC25A15 OTC NAGS CPS1 ASS1 ASL

Molecular functions related to Ornithine Transcarbamylase Deficiency, Hyperammonemia Due to according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 amino acid binding GO:0016597 8.96 OTC ASS1
2 phospholipid binding GO:0005543 8.8 SEC14L2 OTC CPS1
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Sources for Ornithine Transcarbamylase Deficiency, Hyperammonemia Due to

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3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 EFO
18 ExPASy
19 FMA
28 GO
29 GTR
30 HMDB
31 HPO
32 ICD10
33 ICD10 via Orphanet
34 ICD9CM
35 IUPHAR
36 KEGG
37 LifeMap
39 LOVD
41 MedGen
43 MeSH
44 MESH via Orphanet
45 MGI
48 NCI
49 NCIt
50 NDF-RT
53 NINDS
54 Novoseek
56 OMIM
57 OMIM via Orphanet
61 PubMed
63 QIAGEN
68 SNOMED-CT via HPO
69 TGDB
70 Tocris
71 UMLS
72 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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