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Citrullinemia

MedGen UID:
104491
Concept ID:
C0175683
Disease or Syndrome
Synonyms: Argininosuccinate Synthase Deficiency Disease; Argininosuccinate Synthetase Deficiencies; Argininosuccinate Synthetase Deficiency; Argininosuccinic Acid Synthase Deficiency Disease; Argininosuccinic Acid Synthetase Deficiency; Argininosuccinic Acid Synthetase Deficiency Disease; ASS Deficiencies; ASS Deficiency; Citrullinemias; Citrullinuria; Citrullinurias; Deficiencies, Argininosuccinate Synthetase; Deficiency Disease, Argininosuccinate Synthase; Deficiency Disease, Argininosuccinic Acid Synthase; Deficiency, Argininosuccinate Synthetase; Deficiency, ASS
SNOMED CT: Citrullinemia (398680004); Deficiency of citrulline-aspartate ligase (124711003); Deficiency of argininosuccinate synthase (124711003); Argininosuccinate synthase deficiency (124711003)
Modes of inheritance:
Autosomal recessive inheritance
MedGen UID:
141025
Concept ID:
C0441748
Intellectual Product
Source: Orphanet
A mode of inheritance that is observed for traits related to a gene encoded on one of the autosomes (i.e., the human chromosomes 1-22) in which a trait manifests in individuals with two pathogenic alleles, either homozygotes (two copies of the same mutant allele) or compound heterozygotes (whereby each copy of a gene has a distinct mutant allele).
 
Related gene: ASS1
 
Monarch Initiative: MONDO:0015991
OMIM®: 215700
OMIM® Phenotypic series: PS215700
Orphanet: ORPHA187

Definition

Citrullinemia is an autosomal recessively inherited disorder of urea cycle metabolism and ammonia detoxification (see this term) characterized by elevated concentrations of serum citrulline and ammonia. The disease presents with a large range of manifestations including neonatal hyperammonemic encephalopathy with lethargy, seizures and coma; hepatic dysfunction in all age groups; episodes of hyperammonemia and neuropsychiatric symptoms in children or adults, or, can be asymptomatic in some cases (detected in newborn screening programs). Citrullinemia is divided into two main groups that are encoded by different genes: citrullinemia type I (comprised of acute neonatal citrullinemia type I and adult-onset citrullinemia type I) and citrin deficiency (comprised of adult-onset citrullinemia type II and neonatal intrahepatic cholestasis due to citrin deficiency) (see these terms). [from ORDO]

Professional guidelines

PubMed

Hayasaka K
J Inherit Metab Dis 2021 Jan;44(1):110-117. Epub 2020 Aug 26 doi: 10.1002/jimd.12294. PMID: 32740958
ICMR Task Force on Inherited Metabolic Disorders
Indian J Pediatr 2018 Dec;85(12):1050-1054. Epub 2018 Mar 15 doi: 10.1007/s12098-017-2545-4. PMID: 29542068
Wasim M, Awan FR, Khan HN, Tawab A, Iqbal M, Ayesha H
Biochem Genet 2018 Apr;56(1-2):7-21. Epub 2017 Nov 1 doi: 10.1007/s10528-017-9825-6. PMID: 29094226

Recent clinical studies

Etiology

Komatsu M, Tanaka N, Kimura T, Yazaki M
Nutrients 2023 May 12;15(10) doi: 10.3390/nu15102284. PMID: 37242166Free PMC Article
Hassan A
Tremor Other Hyperkinet Mov (N Y) 2023;13:9. Epub 2023 Mar 28 doi: 10.5334/tohm.747. PMID: 37008993Free PMC Article
Men S, Liu S, Zheng Q, Yang S, Mao H, Wang Z, Gu Y, Tang X, Wang L
Mol Genet Genomic Med 2023 Jun;11(6):e2152. Epub 2023 Feb 14 doi: 10.1002/mgg3.2152. PMID: 36787440Free PMC Article
Zielonka M, Kölker S, Gleich F, Stützenberger N, Nagamani SCS, Gropman AL, Hoffmann GF, Garbade SF, Posset R; Urea Cycle Disorders Consortium (UCDC) and the European Registry and Network for Intoxication type Metabolic Diseases (E-IMD) Consortia Study Group
Ann Clin Transl Neurol 2019 Sep;6(9):1858-1871. Epub 2019 Aug 30 doi: 10.1002/acn3.50886. PMID: 31469252Free PMC Article
Wasim M, Awan FR, Khan HN, Tawab A, Iqbal M, Ayesha H
Biochem Genet 2018 Apr;56(1-2):7-21. Epub 2017 Nov 1 doi: 10.1007/s10528-017-9825-6. PMID: 29094226

Diagnosis

Komatsu M, Tanaka N, Kimura T, Yazaki M
Nutrients 2023 May 12;15(10) doi: 10.3390/nu15102284. PMID: 37242166Free PMC Article
Hassan A
Tremor Other Hyperkinet Mov (N Y) 2023;13:9. Epub 2023 Mar 28 doi: 10.5334/tohm.747. PMID: 37008993Free PMC Article
Wasim M, Awan FR, Khan HN, Tawab A, Iqbal M, Ayesha H
Biochem Genet 2018 Apr;56(1-2):7-21. Epub 2017 Nov 1 doi: 10.1007/s10528-017-9825-6. PMID: 29094226
Diez-Fernandez C, Rüfenacht V, Häberle J
Hum Mutat 2017 May;38(5):471-484. Epub 2017 Feb 15 doi: 10.1002/humu.23184. PMID: 28111830
Auron A, Brophy PD
Pediatr Nephrol 2012 Feb;27(2):207-22. Epub 2011 Mar 23 doi: 10.1007/s00467-011-1838-5. PMID: 21431427

Therapy

Huang X
Zhejiang Da Xue Xue Bao Yi Xue Ban 2023 Oct 3;52(6):744-750. doi: 10.3724/zdxbyxb-2023-0378. PMID: 37807629Free PMC Article
Hassan A
Tremor Other Hyperkinet Mov (N Y) 2023;13:9. Epub 2023 Mar 28 doi: 10.5334/tohm.747. PMID: 37008993Free PMC Article
Hayasaka K
J Inherit Metab Dis 2021 Jan;44(1):110-117. Epub 2020 Aug 26 doi: 10.1002/jimd.12294. PMID: 32740958
Lin WX, Zeng HS, Zhang ZH, Mao M, Zheng QQ, Zhao ST, Cheng Y, Chen FP, Wen WR, Song YZ
Sci Rep 2016 Jul 11;6:29732. doi: 10.1038/srep29732. PMID: 27405544Free PMC Article
Leibowitz J, Thoene J, Spector E, Nyhan W
Virchows Arch A Pathol Anat Histol 1978 Mar 10;377(3):249-58. doi: 10.1007/BF00426934. PMID: 148153

Prognosis

Lim LQJ, Adler L, Hajaj E, Soria LR, Perry RB, Darzi N, Brody R, Furth N, Lichtenstein M, Bab-Dinitz E, Porat Z, Melman T, Brandis A, Malitsky S, Itkin M, Aylon Y, Ben-Dor S, Orr I, Pri-Or A, Seger R, Shaul Y, Ruppin E, Oren M, Perez M, Meier J, Brunetti-Pierri N, Shema E, Ulitsky I, Erez A
Nat Metab 2024 Jul;6(7):1294-1309. Epub 2024 Jun 10 doi: 10.1038/s42255-024-01060-5. PMID: 38858597Free PMC Article
Men S, Liu S, Zheng Q, Yang S, Mao H, Wang Z, Gu Y, Tang X, Wang L
Mol Genet Genomic Med 2023 Jun;11(6):e2152. Epub 2023 Feb 14 doi: 10.1002/mgg3.2152. PMID: 36787440Free PMC Article
Tavoulari S, Lacabanne D, Thangaratnarajah C, Kunji ERS
Trends Endocrinol Metab 2022 Aug;33(8):539-553. Epub 2022 Jun 17 doi: 10.1016/j.tem.2022.05.002. PMID: 35725541Free PMC Article
Zielonka M, Kölker S, Gleich F, Stützenberger N, Nagamani SCS, Gropman AL, Hoffmann GF, Garbade SF, Posset R; Urea Cycle Disorders Consortium (UCDC) and the European Registry and Network for Intoxication type Metabolic Diseases (E-IMD) Consortia Study Group
Ann Clin Transl Neurol 2019 Sep;6(9):1858-1871. Epub 2019 Aug 30 doi: 10.1002/acn3.50886. PMID: 31469252Free PMC Article
Curis E, Crenn P, Cynober L
Curr Opin Clin Nutr Metab Care 2007 Sep;10(5):620-6. doi: 10.1097/MCO.0b013e32829fb38d. PMID: 17693747

Clinical prediction guides

Posset R, Garbade SF, Gleich F, Scharre S, Okun JG, Gropman AL, Nagamani SCS, Druck AC, Epp F, Hoffmann GF, Kölker S, Zielonka M; Urea Cycle Disorders Consortium (UCDC); European registry and network for Intoxication type Metabolic Diseases (E-IMD) Consortia Study Group
Genet Med 2024 Apr;26(4):101039. Epub 2023 Dec 3 doi: 10.1016/j.gim.2023.101039. PMID: 38054409
Men S, Liu S, Zheng Q, Yang S, Mao H, Wang Z, Gu Y, Tang X, Wang L
Mol Genet Genomic Med 2023 Jun;11(6):e2152. Epub 2023 Feb 14 doi: 10.1002/mgg3.2152. PMID: 36787440Free PMC Article
Tavoulari S, Lacabanne D, Thangaratnarajah C, Kunji ERS
Trends Endocrinol Metab 2022 Aug;33(8):539-553. Epub 2022 Jun 17 doi: 10.1016/j.tem.2022.05.002. PMID: 35725541Free PMC Article
Zielonka M, Kölker S, Gleich F, Stützenberger N, Nagamani SCS, Gropman AL, Hoffmann GF, Garbade SF, Posset R; Urea Cycle Disorders Consortium (UCDC) and the European Registry and Network for Intoxication type Metabolic Diseases (E-IMD) Consortia Study Group
Ann Clin Transl Neurol 2019 Sep;6(9):1858-1871. Epub 2019 Aug 30 doi: 10.1002/acn3.50886. PMID: 31469252Free PMC Article
Curis E, Crenn P, Cynober L
Curr Opin Clin Nutr Metab Care 2007 Sep;10(5):620-6. doi: 10.1097/MCO.0b013e32829fb38d. PMID: 17693747

Recent systematic reviews

Hassan A
Tremor Other Hyperkinet Mov (N Y) 2023;13:9. Epub 2023 Mar 28 doi: 10.5334/tohm.747. PMID: 37008993Free PMC Article

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