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Citrullinemia type II(CTLN2)

MedGen UID:
350276
Concept ID:
C1863844
Disease or Syndrome
Synonym: Citrullinemia type 2
SNOMED CT: Citrullinemia type II (716863007); Adult onset citrin deficiency (716863007); Adult onset type 2 citrullinemia (716863007)
Modes of inheritance:
 
SLC25A13 (7q21.3)
 
Monarch Initiative: MONDO:0016603
OMIM®: 603471; 603859
Orphanet: ORPHA247585
Authors:

Additional description

From MedlinePlus Genetics
Type II citrullinemia chiefly affects the nervous system, causing confusion, restlessness, memory loss, abnormal behaviors (such as aggression, irritability, and hyperactivity), seizures, and coma. Affected individuals often have specific food preferences, preferring protein-rich and fatty foods and avoiding carbohydrate-rich foods. The signs and symptoms of this disorder typically appear during adulthood (adult-onset) and can be triggered by certain medications, infections, surgery, and alcohol intake. These signs and symptoms can be life-threatening in people with adult-onset type II citrullinemia.

Type I citrullinemia (also known as classic citrullinemia) usually becomes evident in the first few days of life. Affected infants typically appear normal at birth, but as ammonia builds up, they experience a progressive lack of energy (lethargy), poor feeding, vomiting, seizures, and loss of consciousness. Some affected individuals develop serious liver problems. The health problems associated with type I citrullinemia are life-threatening in many cases. Less commonly, a milder form of type I citrullinemia can develop later in childhood or adulthood. This later-onset form is associated with intense headaches, blind spots (scotomas), problems with balance and muscle coordination (ataxia), and lethargy. Some people with gene mutations that cause type I citrullinemia never experience signs and symptoms of the disorder.

Citrullinemia is an inherited disorder that causes ammonia and other toxic substances to accumulate in the blood. Two types of citrullinemia have been described; they have different signs and symptoms and are caused by mutations in different genes.

Adult-onset type II citrullinemia may also develop in people who as infants had a liver disorder called neonatal intrahepatic cholestasis caused by citrin deficiency (NICCD). This liver condition is also known as neonatal-onset type II citrullinemia. NICCD blocks the flow of bile (a digestive fluid produced by the liver) and prevents the body from processing certain nutrients properly. In many cases, the signs and symptoms of NICCD go away within a year. In rare cases, affected individuals develop other signs and symptoms in early childhood after seeming to recover from NICCD, including delayed growth, extreme tiredness (fatigue), specific food preferences (mentioned above), and abnormal amounts of fats (lipids) in the blood (dyslipidemia). This condition is known as failure to thrive and dyslipidemia caused by citrin deficiency (FTTDCD). Years or even decades later, some people with NICCD or FTTDCD develop the features of adult-onset type II citrullinemia.  https://medlineplus.gov/genetics/condition/citrullinemia

Clinical features

From HPO

Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  

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
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
Kimura N, Kubo N, Narumi S, Toyoki Y, Ishido K, Kudo D, Umehara M, Yakoshi Y, Hakamada K
Transplant Proc 2013 Nov;45(9):3432-7. doi: 10.1016/j.transproceed.2013.06.016. PMID: 24182831

Curated

American College of Medical Genetics and Genomics, Newborn Screening ACT Sheet, [Elevated Citrulline], Amino Acidemia/Urea Cycle Disorder, 2022

American College of Medical Genetics and Genomics, Elevated Citrulline: Amino Acidemia Algorithm, 2022

Recent clinical studies

Etiology

Kim MJ, Kim SY, Lee JS, Kang S, Park LJ, Choi W, Jung JY, Kim T, Park SS, Ko JM, Seong MW, Chae JH
Ann Lab Med 2023 May 1;43(3):280-289. Epub 2022 Dec 22 doi: 10.3343/alm.2023.43.3.280. PMID: 36544340Free PMC Article
Palmieri F, Scarcia P, Monné M
Biomolecules 2020 Apr 23;10(4) doi: 10.3390/biom10040655. PMID: 32340404Free PMC Article
Moreira-Silva H, Maio I, Bandeira A, Gomes-Martins E, Santos-Silva E
Eur J Pediatr 2019 Apr;178(4):515-523. Epub 2019 Jan 28 doi: 10.1007/s00431-019-03328-5. PMID: 30693370
Waisbren SE, Gropman AL; Members of the Urea Cycle Disorders Consortium (UCDC), Batshaw ML
J Inherit Metab Dis 2016 Jul;39(4):573-84. Epub 2016 May 23 doi: 10.1007/s10545-016-9942-0. PMID: 27215558Free PMC Article
Song YZ, Zhang ZH, Lin WX, Zhao XJ, Deng M, Ma YL, Guo L, Chen FP, Long XL, He XL, Sunada Y, Soneda S, Nakatomi A, Dateki S, Ngu LH, Kobayashi K, Saheki T
PLoS One 2013;8(9):e74544. Epub 2013 Sep 19 doi: 10.1371/journal.pone.0074544. PMID: 24069319Free PMC Article

Diagnosis

Liu J, Lin S, Guan S, Chen Q, Wang X, He Y, Qi Y, Feng J, Liu Y
Medicine (Baltimore) 2023 Dec 8;102(49):e36293. doi: 10.1097/MD.0000000000036293. PMID: 38065893Free PMC Article
Kim MJ, Kim SY, Lee JS, Kang S, Park LJ, Choi W, Jung JY, Kim T, Park SS, Ko JM, Seong MW, Chae JH
Ann Lab Med 2023 May 1;43(3):280-289. Epub 2022 Dec 22 doi: 10.3343/alm.2023.43.3.280. PMID: 36544340Free PMC Article
Sarker SK, Islam MT, Biswas A, Bhuyan GS, Sultana R, Sultana N, Rakhshanda S, Begum MN, Rahat A, Yeasmin S, Khanam M, Saha AK, Noor FA, Sajib AA, Islam ABMMK, Qadri SK, Shahidullah M, Mannan MA, Muraduzzaman AKM, Shirin T, Rahman SM, Qadri SS, Saha N, Akhteruzzaman S, Qadri F, Mannoor K
Biomed Res Int 2019;2019:3460902. Epub 2019 Jan 6 doi: 10.1155/2019/3460902. PMID: 30723736Free PMC Article
Moreira-Silva H, Maio I, Bandeira A, Gomes-Martins E, Santos-Silva E
Eur J Pediatr 2019 Apr;178(4):515-523. Epub 2019 Jan 28 doi: 10.1007/s00431-019-03328-5. PMID: 30693370
Kuhara T
J Chromatogr B Analyt Technol Biomed Life Sci 2002 Dec 5;781(1-2):497-517. doi: 10.1016/s1570-0232(02)00670-0. PMID: 12450676

Therapy

Avdjieva-Tzavella DM, Ivanova MB, Todorov TP, Todorova AP, Panteleeva EI, Tincheva SS, Lazarova EA, Kathom HM, Yaneva PG, Tincheva RS
Genet Couns 2014;25(3):271-6. PMID: 25365849

Prognosis

Kim MJ, Kim SY, Lee JS, Kang S, Park LJ, Choi W, Jung JY, Kim T, Park SS, Ko JM, Seong MW, Chae JH
Ann Lab Med 2023 May 1;43(3):280-289. Epub 2022 Dec 22 doi: 10.3343/alm.2023.43.3.280. PMID: 36544340Free PMC Article
Avdjieva-Tzavella DM, Ivanova MB, Todorov TP, Todorova AP, Panteleeva EI, Tincheva SS, Lazarova EA, Kathom HM, Yaneva PG, Tincheva RS
Genet Couns 2014;25(3):271-6. PMID: 25365849
Tsai CW, Yang CC, Chen HL, Hwu WL, Wu MZ, Liu KL, Wu MS
J Formos Med Assoc 2006 Oct;105(10):852-6. doi: 10.1016/S0929-6646(09)60274-6. PMID: 17000460

Clinical prediction guides

Choi JJ, Kim HS, Lee KC, Shin Y, Jo YY
BMC Anesthesiol 2016 Oct 11;16(1):92. doi: 10.1186/s12871-016-0253-7. PMID: 27724842Free PMC Article
Häberle J, Pauli S, Schmidt E, Schulze-Eilfing B, Berning C, Koch HG
Mol Genet Metab 2003 Nov;80(3):302-6. doi: 10.1016/j.ymgme.2003.08.002. PMID: 14680976

Supplemental Content

Table of contents

    Clinical resources

    Practice guidelines

    • PubMed
      See practice and clinical guidelines in PubMed. The search results may include broader topics and may not capture all published guidelines. See the FAQ for details.

    Curated

    • ACMG, ACT Sheet, 2022
      American College of Medical Genetics and Genomics, Newborn Screening ACT Sheet, [Elevated Citrulline], Amino Acidemia/Urea Cycle Disorder, 2022
    • ACMG Algorithm, 2022
      American College of Medical Genetics and Genomics, Elevated Citrulline: Amino Acidemia Algorithm, 2022

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