Details of Disease

General Information of Disease (ID: DIS2UURN)

• Disease Name: Citrullinemia type II
• Synonyms: CTLN2; adult-onset type 2 citrullinemia; citrullinemia type 2; adult-onset citrin deficiency; citrullinemia type II; adult-onset type II citrullinemia
• Definition: Citrullinemia type II is a severe subtype of citrin deficiency characterized clinically by adult onset (20 and 50 years of age), recurrent episodes of hyperammonemia and associated neuropsychiatric symptoms such as nocturnal delirium, confusion, restlessness, disorientation, drowsiness, memory loss, abnormal behavior (aggression, irritability, and hyperactivity), seizures, and coma.
• Disease Hierarchy:
  DISIJZ2R: Citrin deficiency
  DIS2UURN: Citrullinemia type II
• Disease Identifiers:
  MONDO ID: MONDO_0016603
  MESH ID: C538053
  UMLS CUI: C1863844
  OMIM ID: 603471
  MedGen ID: 350276
  Orphanet ID: 247585
  SNOMED CT ID: 716863007

Molecular Interaction Atlas (MIA) of This Disease

This Disease Is Related to 1 DTT Molecule(s)

Gene Name	DTT ID	Evidence Level	Mode of Inheritance	REF
SLC10A1	TTWZRY5	moderate	Altered Expression	[1]

This Disease Is Related to 3 DTP Molecule(s)

Gene Name	DTP ID	Evidence Level	Mode of Inheritance	REF
SLC25A12	DT85HYR	Strong	Genetic Variation	[2]
SLC25A33	DTI48RF	Strong	Biomarker	[3]
SLC25A37	DTLBGTZ	Strong	Genetic Variation	[4]

This Disease Is Related to 4 DOT Molecule(s)

Gene Name	DOT ID	Evidence Level	Mode of Inheritance	REF
SLC25A13	OTTZVSK6	Supportive	Autosomal recessive	[5]
ACOX1	OTM0A0DY	Strong	Biomarker	[6]
GPD2	OTV232Y7	Strong	Biomarker	[7]
SPINK1	OTSUVAL2	Strong	Altered Expression	[8]

References

• [1] Sodium Taurocholate Cotransporting Polypeptide (NTCP) Deficiency Hidden Behind Citrin Deficiency in Early Infancy: A Report of Three Cases.Front Genet. 2019 Nov 7;10:1108. doi: 10.3389/fgene.2019.01108. eCollection 2019.
• [2] Citrin and aralar1 are Ca(2+)-stimulated aspartate/glutamate transporters in mitochondria.EMBO J. 2001 Sep 17;20(18):5060-9. doi: 10.1093/emboj/20.18.5060.
• [3] Genomic structure of the adult-onset type II citrullinemia gene, SLC25A13, and cloning and expression of its mouse homologue.Genomics. 1999 Dec 1;62(2):289-92. doi: 10.1006/geno.1999.6006.
• [4] Mitochondrial aspartate glutamate carrier (citrin) deficiency as the cause of adult-onset type II citrullinemia (CTLN2) and idiopathic neonatal hepatitis (NICCD).J Hum Genet. 2002;47(7):333-41. doi: 10.1007/s100380200046.
• [5] Citrin Deficiency. 2005 Sep 16 [updated 2017 Aug 10]. In: Adam MP, Feldman J, Mirzaa GM, Pagon RA, Wallace SE, Bean LJH, Gripp KW, Amemiya A, editors. GeneReviews(?) [Internet]. Seattle (WA): University of Washington, Seattle; 1993C2024.
• [6] Steatogenesis in adult-onset type II citrullinemia is associated with down-regulation of PPAR.Biochim Biophys Acta. 2015 Mar;1852(3):473-81. doi: 10.1016/j.bbadis.2014.12.011. Epub 2014 Dec 20.
• [7] Effects of supplementation on food intake, body weight and hepatic metabolites in the citrin/mitochondrial glycerol-3-phosphate dehydrogenase double-knockout mouse model of human citrin deficiency.Mol Genet Metab. 2012 Nov;107(3):322-9. doi: 10.1016/j.ymgme.2012.07.021. Epub 2012 Aug 2.
• [8] Treatment of a citrin-deficient patient at the early stage of adult-onset type II citrullinaemia with arginine and sodium pyruvate.J Inherit Metab Dis. 2008 Dec;31 Suppl 2:S343-7. doi: 10.1007/s10545-008-0914-x. Epub 2008 Oct 29.