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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). Autosomal recessive inheritance (Orphanet)

Related gene: Gene(s) associated with related conditions. For conditions in a hierarchy, the parent condition will list the genes associated with the children conditions.	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]

Term Hierarchy

GTR
MeSH
Orphanet

CClinical test, RResearch test, OOMIM, GGeneReviews, VClinVar

Congenital, Hereditary, and Neonatal Diseases and Abnormalities
- Inborn genetic diseases
  - Inborn errors of metabolism
    - Brain Diseases, Metabolic, Inborn
      - Disorder of the urea cycle metabolism
        Citrullinemia
        Citrullinemia type I
        Acute neonatal citrullinemia type I
        Adult-onset citrullinemia type I
        Citrullinemia type II
        Citrullinemia, type II, adult-onset
        Neonatal intrahepatic cholestasis due to citrin deficiency

Follow this link to review classifications for Citrullinemia in Orphanet.

Professional guidelines

PubMed

Metabolic basis and treatment of citrin deficiency.

Hayasaka K
J Inherit Metab Dis 2021 Jan;44(1):110-117. Epub 2020 Aug 26 doi: 10.1002/jimd.12294. PMID: 32740958

High Risk Stratified Neonatal Screening.

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

Aminoacidopathies: Prevalence, Etiology, Screening, and Treatment Options.

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

See all (42)

Recent clinical studies

Etiology

Citrin Deficiency: Clinical and Nutritional Features.

Komatsu M, Tanaka N, Kimura T, Yazaki M
Nutrients 2023 May 12;15(10) doi: 10.3390/nu15102284. PMID: 37242166 Free PMC Article

Episodic Ataxias: Primary and Secondary Etiologies, Treatment, and Classification Approaches.

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

Incidence and genetic variants of inborn errors of metabolism identified through newborn screening: A 7-year study in eastern coastal areas of China.

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: 36787440 Free PMC Article

Early prediction of phenotypic severity in Citrullinemia Type 1.

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: 31469252 Free PMC Article

Aminoacidopathies: Prevalence, Etiology, Screening, and Treatment Options.

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

See all (114)

Diagnosis

Citrin Deficiency: Clinical and Nutritional Features.

Komatsu M, Tanaka N, Kimura T, Yazaki M
Nutrients 2023 May 12;15(10) doi: 10.3390/nu15102284. PMID: 37242166 Free PMC Article

Episodic Ataxias: Primary and Secondary Etiologies, Treatment, and Classification Approaches.

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

Aminoacidopathies: Prevalence, Etiology, Screening, and Treatment Options.

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

Mutations in the Human Argininosuccinate Synthetase (ASS1) Gene, Impact on Patients, Common Changes, and Structural Considerations.

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

Hyperammonemia in review: pathophysiology, diagnosis, and treatment.

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

See all (274)

Therapy

Treatment and management for children with urea cycle disorder in chronic stage.

Huang X
Zhejiang Da Xue Xue Bao Yi Xue Ban 2023 Oct 3;52(6):744-750. doi: 10.3724/zdxbyxb-2023-0378. PMID: 37807629 Free PMC Article

Episodic Ataxias: Primary and Secondary Etiologies, Treatment, and Classification Approaches.

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

Metabolic basis and treatment of citrin deficiency.

Hayasaka K
J Inherit Metab Dis 2021 Jan;44(1):110-117. Epub 2020 Aug 26 doi: 10.1002/jimd.12294. PMID: 32740958

Molecular diagnosis of pediatric patients with citrin deficiency in China: SLC25A13 mutation spectrum and the geographic distribution.

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: 27405544 Free PMC Article

Citrullinemia.

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

See all (77)

Prognosis

Incidence and genetic variants of inborn errors of metabolism identified through newborn screening: A 7-year study in eastern coastal areas of China.

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: 36787440 Free PMC Article

Pathogenic variants of the mitochondrial aspartate/glutamate carrier causing citrin deficiency.

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: 35725541 Free PMC Article

Early prediction of phenotypic severity in Citrullinemia Type 1.

Citrulline and the gut.

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

The human argininosuccinate synthetase locus and citrullinemia.

Beaudet AL, O'Brien WE, Bock HG, Freytag SO, Su TS
Adv Hum Genet 1986;15:161-96, 291-2. doi: 10.1007/978-1-4615-8356-1_3. PMID: 3513483

See all (115)

Clinical prediction guides

Severity-adjusted evaluation of liver transplantation on health outcomes in urea cycle disorders.

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

Incidence and genetic variants of inborn errors of metabolism identified through newborn screening: A 7-year study in eastern coastal areas of China.

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: 36787440 Free PMC Article

Pathogenic variants of the mitochondrial aspartate/glutamate carrier causing citrin deficiency.

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: 35725541 Free PMC Article

Early prediction of phenotypic severity in Citrullinemia Type 1.

Citrulline and the gut.

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

See all (104)