Details of Disease

General Information of Disease (ID: DISITN7S)

• Disease Name: Ornithine translocase deficiency
• Synonyms: HHH; HHHS; Hhh syndrome; ornithine translocase deficiency syndrome; hyperornithinemia-hyperammonemia-homocitrullinuria syndrome; ornithine translocase deficiency; HHH syndrome; ornithine carrier deficiency; triple H syndrome; hyperornithinemia-hyperammonemia-homocitrullinemia syndrome; hyperornithinemia-hyperammonemia-homocitrullinuria (HHH) syndrome; ORNT1 deficiency
• Definition: A rare, genetic disorder of urea cycle metabolism characterized by either a neonatal-onset with manifestations of lethargy, poor feeding, vomiting and tachypnea or, more commonly, presentations in infancy, childhood or adulthood with chronic neurocognitive deficits, acute encephalopathy and/or coagulation defects or other chronic liver dysfunction.
• Disease Hierarchy:
  DIS6SVEE: Syndromic disease
  DISKD7HM: Urea cycle disorder or inherited hyperammonemia
  DISITN7S: Ornithine translocase deficiency
• Disease Identifiers:
  MONDO ID: MONDO_0009393
  MESH ID: C538380
  UMLS CUI: C0268540
  OMIM ID: 238970
  MedGen ID: 82815
  Orphanet ID: 415
  SNOMED CT ID: 30287008

Molecular Interaction Atlas (MIA) of This Disease

This Disease Is Related to 2 DTT Molecule(s)

Gene Name	DTT ID	Evidence Level	Mode of Inheritance	REF
CPS1	TT42M75	Strong	Biomarker	[1]
OAT	TTTSCQ2	Strong	Biomarker	[2]

This Disease Is Related to 2 DTP Molecule(s)

Gene Name	DTP ID	Evidence Level	Mode of Inheritance	REF
SLC25A29	DT96BT4	Strong	Biomarker	[3]
SLC25A15	DTHEMTY	Definitive	Autosomal recessive	[4]

This Disease Is Related to 3 DOT Molecule(s)

Gene Name	DOT ID	Evidence Level	Mode of Inheritance	REF
ALDH18A1	OT6W40XU	Strong	Biomarker	[5]
ORC1	OTHWU8IJ	Strong	Genetic Variation	[6]
SLC25A15	OTOA9232	Definitive	Autosomal recessive	[4]

References

• [1] 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.
• [2] Comparison of ornithine metabolism in hyperornithinaemia-hyperammonaemia-homocitrullinuria syndrome, lysinuric protein intolerance and gyrate atrophy fibroblasts.J Inherit Metab Dis. 1989;12(1):33-40. doi: 10.1007/BF01805528.
• [3] The human and mouse SLC25A29 mitochondrial transporters rescue the deficient ornithine metabolism in fibroblasts of patients with the hyperornithinemia-hyperammonemia-homocitrullinuria (HHH) syndrome.Pediatr Res. 2009 Jul;66(1):35-41. doi: 10.1203/PDR.0b013e3181a283c1.
• [4] 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.
• [5] Hereditary Spastic Paraplegia Is a Common Phenotypic Finding in ARG1 Deficiency, P5CS Deficiency and HHH Syndrome: Three Inborn Errors of Metabolism Caused by Alteration of an Interconnected Pathway of Glutamate and Urea Cycle Metabolism.Front Neurol. 2019 Feb 22;10:131. doi: 10.3389/fneur.2019.00131. eCollection 2019.
• [6] The mitochondrial ornithine transporter. Bacterial expression, reconstitution, functional characterization, and tissue distribution of two human isoforms.J Biol Chem. 2003 Aug 29;278(35):32778-83. doi: 10.1074/jbc.M302317200. Epub 2003 Jun 13.