Details of Disease

General Information of Disease (ID: DIS3DOIC)

• Disease Name: Ornithine transcarbamylase deficiency
• Synonyms: ornithine transcarbamylase deficiency, hyperammonemia due to; valproate sensitivity; ornithine carbamoyltransferase deficiency disease; OTCD; ornithine transcarbamylase deficiency; OCT deficiency; OTC deficiency; ornithine carbamoyltransferase deficiency; deficiency of citrulline phosphorylase
• Disease Class: 5C50: Metabolism inborn error
• Definition: Ornithine transcarbamylase deficiency (OTCD) is a disorder of urea cycle metabolism and ammonia detoxification characterized by either a severe, neonatal-onset disease found almost exclusively in males, or later-onset (partial) forms of the disease. Both present with episodes of hyperammonemia that can be fatal and which can lead to neurological complications.
• Disease Hierarchy:
  DISKD7HM: Urea cycle disorder or inherited hyperammonemia
  DIS3DOIC: Ornithine transcarbamylase deficiency
• ICD Code:
  ICD-11: ICD-11: 5C50.AY
  Expand ICD-11: '5C50.AY
• Disease Identifiers:
  MONDO ID: MONDO_0010703
  MESH ID: D020163
  UMLS CUI: C0268542
  OMIM ID: 311250
  MedGen ID: 75692
  Orphanet ID: 664
  SNOMED CT ID: 80908008

Drug-Interaction Atlas (DIA) of This Disease

This Disease is Treated as An Indication in 3 Approved Drug(s)

Drug Name	Drug ID	Highest Status	Drug Type	REF
Benzoic Acid	DMKB9FI	Approved	Small molecular drug	[1]
Lactulose	DMSAOWQ	Approved	Small molecular drug	[2]
Phenylacetic acid	DMQ95GE	Approved	Small molecular drug	[3]

This Disease is Treated as An Indication in 3 Clinical Trial Drug(s)

Drug Name	Drug ID	Highest Status	Drug Type	REF
Avalotcagene ontaparvovec	DMAOHT4	Phase 3	Gene therapy	[4]
ARCT-810	DM91F9I	Phase 2	mRNA therapy	[5]
DTX301	DM8M71U	Phase 1/2	Gene therapy	[6]

This Disease is Treated as An Indication in 1 Preclinical Drug(s)

Drug Name	Drug ID	Highest Status	Drug Type	REF
mRNA-3139	DMYWW5Z	Preclinical	Vaccine	[7]

This Disease is Treated as An Indication in 2 Investigative Drug(s)

Drug Name	Drug ID	Highest Status	Drug Type	REF
E1/E4-deleted adenoviral vector	DMMY698	Investigative	NA	[8]
Heterologous liver-derived stem cells	DM6EF2Z	Investigative	NA	[8]

Molecular Interaction Atlas (MIA) of This Disease

This Disease Is Related to 6 DTT Molecule(s)

Gene Name	DTT ID	Evidence Level	Mode of Inheritance	REF
CPS1	TT42M75	Strong	Genetic Variation	[9]
F7	TTF0EGX	Strong	Genetic Variation	[10]
RPGR	TTHBDA9	Strong	Biomarker	[11]
TSPAN7	TTMT6VE	Strong	Genetic Variation	[12]
OTC	TT5KIO9	Definitive	X-linked	[13]
OTC	TT5KIO9	Definitive	Altered Expression	[14]

This Disease Is Related to 1 DTP Molecule(s)

Gene Name	DTP ID	Evidence Level	Mode of Inheritance	REF
SLC25A15	DTHEMTY	Strong	Genetic Variation	[15]

This Disease Is Related to 2 DOT Molecule(s)

Gene Name	DOT ID	Evidence Level	Mode of Inheritance	REF
PM20D1	OTXXNQ5K	Strong	Altered Expression	[16]
OTC	OTJ57GGA	Definitive	X-linked	[13]

References

• [1] Ornithine transcarbamylase deficiency: a urea cycle defect. Eur J Paediatr Neurol. 2003;7(3):115-21.
• [2] Lactulose FDA Label
• [3] Glycerol Phenylbutyrate (Ravicti). Ottawa (ON): Canadian Agency for Drugs and Technologies in Health; 2017 Apr.
• [4] ClinicalTrials.gov (NCT05345171) A Phase 3, Randomized, Double-blind, Placebo-controlled Study of Adeno-associated Virus (AAV) Serotype 8 (AAV8)-Mediated Gene Transfer of Human Ornithine Transcarbamylase (OTC) in Patients With Late-onset OTC Deficiency. U.S.National Institutes of Health.
• [5] Clinical pipeline report, company report or official report of Arcturus Therapeutics
• [6] ClinicalTrials.gov (NCT02991144) Safety and Dose-Finding Study of DTX301 (scAAV8OTC) in Adults With Late-Onset OTC Deficiency (CAPtivate). U.S. National Institutes of Health.
• [7] Clinical pipeline report, company report or official report of Moderna
• [8] The ChEMBL database in 2017. Nucleic Acids Res. 2017 Jan 4;45(D1):D945-D954.
• [9] Decreased plasma l-arginine levels in organic acidurias (MMA and PA) and decreased plasma branched-chain amino acid levels in urea cycle disorders as a potential cause of growth retardation: Options for treatment.Mol Genet Metab. 2019 Apr;126(4):397-405. doi: 10.1016/j.ymgme.2019.02.003. Epub 2019 Feb 25.
• [10] Liver after hepatocyte transplantation for liver-based metabolic disorders in children.Cell Transplant. 2008;17(12):1403-14. doi: 10.3727/096368908787648083.
• [11] Symptoms of OTC deficiency but not DMD in a female carrier of an Xp21.1 deletion including the genes for dystrophin and OTC.Eur J Pediatr. 2007 Jul;166(7):743-5. doi: 10.1007/s00431-006-0303-0. Epub 2006 Nov 8.
• [12] Complete deletion of ornithine transcarbamylase gene confirmed by CGH array of X chromosome.J Inherit Metab Dis. 2007 Oct;30(5):813. doi: 10.1007/s10545-007-0578-y. Epub 2007 Jun 14.
• [13] Technical standards for the interpretation and reporting of constitutional copy-number variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics (ACMG) and the Clinical Genome Resource (ClinGen). Genet Med. 2020 Feb;22(2):245-257. doi: 10.1038/s41436-019-0686-8. Epub 2019 Nov 6.
• [14] Targeted mRNA Therapy for Ornithine Transcarbamylase Deficiency.Mol Ther. 2018 Mar 7;26(3):801-813. doi: 10.1016/j.ymthe.2017.12.024. Epub 2018 Jan 4.
• [15] Cloning and characterization of human ORNT2: a second mitochondrial ornithine transporter that can rescue a defective ORNT1 in patients with the hyperornithinemia-hyperammonemia-homocitrullinuria syndrome, a urea cycle disorder.Mol Genet Metab. 2003 Aug;79(4):257-71. doi: 10.1016/s1096-7192(03)00105-7.
• [16] Genetic analysis of carbamoylphosphate synthetase I and ornithine transcarbamylase deficiency using fibroblasts.Eur J Pediatr. 2001 May;160(5):283-7. doi: 10.1007/s004310100725.