Details of Disease

General Information of Disease (ID: DIS5O5V0)

Disease Name	Urea cycle disorder
Synonyms	disorder of urea cycle metabolism and ammonia detoxification; UCD; inborn urea cycle disorder; urea cycle defect; inborn disorder of urea cycle metabolism and ammonia detoxification; disorder of metabolism of ornithine, citrulline, argininosuccinic acid, arginine and ammonia; urea cycle metabolism disorder; disorder of urea cycle metabolism; urea cycle disorders
Disease Class	5C50: Metabolism inborn error
Definition	A genetic inborn error of metabolism characterized by the deficiency of one of the enzymes necessary for the urea cycle. It results in accumulation of ammonia in the body.
Disease Hierarchy	DISFWXCM: Inborn disorder of amino acid metabolism DISWE0E0: Inborn disorder of amino acid and other organic acid metabolism DIS5O5V0: Urea cycle disorder
ICD Code	ICD-11 ICD-11: 5C50.A ICD-10 ICD-10: E72.2 ICD-9 ICD-9: 270.6 Expand ICD-11 '5C50.A Expand ICD-10 'E72.2 Expand ICD-9 270.6
Disease Identifiers	MONDO ID MONDO_0004739 MESH ID D056806 UMLS CUI C0154246 MedGen ID 57586 Orphanet ID 79167 SNOMED CT ID 36444000

Drug-Interaction Atlas (DIA) of This Disease

Drug-Interaction Atlas (DIA)

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

Drug Name	Drug ID	Highest Status	Drug Type	REF
Sodium phenylbutyrate	DMXLBCQ	Approved	Small molecular drug	[1]
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This Disease is Treated as An Indication in 4 Clinical Trial Drug(s)

Drug Name	Drug ID	Highest Status	Drug Type	REF
Heterologous liver cell therapy	DMTA76F	Phase 2	NA	[2]
Human heterologous liver cells	DM4LH64	Phase 2	NA	[2]
KB195	DMEB2XW	Phase 2	NA	[3]
Phenylbutyrate	DMBHPDW	Phase 2	Small molecular drug	[4]
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Molecular Interaction Atlas (MIA) of This Disease

Molecular Interaction Atlas (MIA)

This Disease Is Related to 3 DTT Molecule(s)

Gene Name	DTT ID	Evidence Level	Mode of Inheritance	REF
OTC	TT5KIO9	Limited	Biomarker	[5]
ARG1	TT7ZQEV	Strong	Genetic Variation	[6]
CPS1	TT42M75	Strong	Genetic Variation	[7]
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This Disease Is Related to 2 DTP Molecule(s)

Gene Name	DTP ID	Evidence Level	Mode of Inheritance	REF
SLC25A15	DTHEMTY	Strong	Genetic Variation	[8]
SLC25A2	DTDPJ3F	Strong	Biomarker	[8]
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This Disease Is Related to 1 DME Molecule(s)

Gene Name	DME ID	Evidence Level	Mode of Inheritance	REF
NAGS	DEGI1A9	Strong	Biomarker	[9]
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This Disease Is Related to 3 DOT Molecule(s)

Gene Name	DOT ID	Evidence Level	Mode of Inheritance	REF
ASL	OTI2NGQR	Limited	Biomarker	[10]
ASS1	OT4ZMG0Q	Limited	Altered Expression	[11]
ARID4B	OTYLPILE	Strong	Altered Expression	[12]
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References

1	Sodium phenylbutyrate FDA Label
2	ClinicalTrials.gov (NCT01195753) Human Heterologous Liver Cells for Infusion in Children With Urea Cycle Disorders. U.S. National Institutes of Health.
3	ClinicalTrials.gov (NCT03933410) UNLOCKED: A Phase 2, Open-label Trial With KB195 in Subjects With a Urea Cycle Disorder (UNLOCKED). U.S. National Institutes of Health.
4	URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 8480).
5	Early liver transplantation in neonatal-onset and moderate urea cycle disorders may lead to normal neurodevelopment.Metab Brain Dis. 2018 Oct;33(5):1517-1523. doi: 10.1007/s11011-018-0259-6. Epub 2018 Jun 11.
6	Arginase I mRNA therapy - a novel approach to rescue arginase 1 enzyme deficiency.RNA Biol. 2018;15(7):914-922. doi: 10.1080/15476286.2018.1475178. Epub 2018 Jul 24.
7	Carbamoyl phosphate synthetase 1 deficiency diagnosed by whole exome sequencing.J Clin Lab Anal. 2018 Feb;32(2):e22241. doi: 10.1002/jcla.22241. Epub 2017 Apr 26.
8	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.
9	Favourable long-term outcome after immediate treatment of neonatal hyperammonemia due to N-acetylglutamate synthase deficiency.Eur J Pediatr. 2010 Feb;169(2):197-9. doi: 10.1007/s00431-009-1006-0. Epub 2009 Jun 17.
10	Argininosuccinate neurotoxicity and prevention by creatine in argininosuccinate lyase deficiency: An in vitro study in rat three-dimensional organotypic brain cell cultures.J Inherit Metab Dis. 2019 Nov;42(6):1077-1087. doi: 10.1002/jimd.12090. Epub 2019 Apr 14.
11	Citrullinemia Type 1: Behavioral Improvement with Late Liver Transplantation.Indian J Pediatr. 2019 Jul;86(7):639-641. doi: 10.1007/s12098-019-02905-8. Epub 2019 Mar 8.
12	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.