CIT
MCID: CTR001
MIFTS: 57

Citrullinemia (CIT) malady

Genetic diseases, Rare diseases categories

Summaries for Citrullinemia

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9Disease Ontology, 22Genetics Home Reference, 66Wikipedia, 48OMIM, 34MalaCards
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Genetics Home Reference:22 Citrullinemia is an inherited disorder that causes ammonia and other toxic substances to accumulate in the blood. Two forms of citrullinemia have been described; they have different signs and symptoms and are caused by mutations in different genes.

MalaCards: Citrullinemia, also known as ass deficiency, is related to adult-onset citrullinemia type ii and reye syndrome. An important gene associated with Citrullinemia is ASS1 (argininosuccinate synthase 1), and among its related pathways are Alanine, aspartate and glutamate metabolism and Glucose metabolism. The compounds Canavaninosuccinate and L-Aspartic acid have been mentioned in the context of this disorder. Affiliated tissues include liver, brain and testes, and related mouse phenotype renal/urinary system.

Disease Ontology:9 An urea cycle disorder that involves the accumulation of ammonia in the blood.

Wikipedia:66 Citrullinemia is an autosomal recessive urea cycle disorder that causes ammonia and other toxic... more...

Description from OMIM:48 215700

Aliases & Classifications for Citrullinemia

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Sources:
9Disease Ontology, 10diseasecard, 22Genetics Home Reference, 48OMIM, 46Novoseek, 50Orphanet, 63UMLS, 59SNOMED-CT, 41NCIt, 36MeSH, 37MESH via Orphanet, 27ICD10 via Orphanet, 60SNOMED-CT via Orphanet, 64UMLS via Orphanet
See all sources

Classifications:

Malacards categories (disease lists): (See all malacards categories)
Global: Genetic diseases, Rare diseases


Characteristics (Orphanet epidemiological data):

50
citrullinemia:
Inheritance: Autosomal recessive; Age of onset: Childhood
ass deficiency:
Inheritance: Autosomal recessive; Prevalence: 1-9/100000; Age of onset: Variable


Aliases & Descriptions:

citrullinemia 9 10 22 48 46 50 63
ass deficiency 9 50
citrullinuria 9 22
argininosuccinic acid synthetase deficiency 50
deficiency of citrulline-aspartate ligase 9
argininosuccinic acid synthase deficiency 50
argininosuccinate synthetase deficiency 50
argininosuccinate synthase deficiency 50
classic citrullinemia 50
citrullinemia type i 50
citrullinemia type 1 50
ctln1 50
cit 22


External Ids:

Disease Ontology9 DOID:9273
NCIt41 C84639
MeSH36 D020159
OMIM48 215700
MESH via Orphanet37 D020159
ICD10 via Orphanet27 E72.2
SNOMED-CT via Orphanet60 398680004, 124711003
UMLS via Orphanet64 C0175683

Related Diseases for Citrullinemia

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Sources:
18GeneCards, 19GeneDecks
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Diseases in the Citrullinemia family:

Citrullinemia Type I Adult-Onset Citrullinemia Type Ii
Adult-Onset Citrullinemia Type I

Diseases related to Citrullinemia via text searches within MalaCards or GeneCards/GeneDecks gene sharing:

(show top 50)    (show all 84)
idRelated DiseaseScoreTop Affiliating Genes
1adult-onset citrullinemia type ii31.0ASS1, SLC25A13
2reye syndrome30.4OTC, PC
3citrin deficiency30.4SLC25A13
4argininosuccinic aciduria30.4ASL, OTC
5hepatocellular carcinoma30.2OTC, SLC25A13, ASS1
6hepatitis30.1ASL, OTC
7urea cycle disorder30.0ASL, ASS1
8carbamoyl phosphate synthetase i deficiency disease30.0OTC, ASS1
9fatty liver disease29.9ASS1, PC, SLC25A13
10ornithine carbamoyltransferase deficiency29.9ASL, ASS1, OTC
11hyperargininemia29.9ASS1, ASL, OTC
12liver cirrhosis29.9SLC25A13, ASS1, OTC
13parkinson's disease10.7
14citrullinemia type i10.6
15dementia10.4
16tremor10.4
17acute myeloid leukemia with t(8;21)(q22;q22) translocation10.3
18neonatal intrahepatic cholestasis caused by citrin deficiency10.3
19schizophrenia10.3
20acute neonatal citrullinemia type i10.3
21adult-onset citrullinemia type i10.3
22essential tremor10.3
23dystonia10.3
24pancreatitis10.3
25multiple system atrophy10.2
26progressive supranuclear palsy10.2
27meningioma10.2
28obsessive-compulsive disorder10.1
29cerebritis10.1
30bipolar disorder10.1
31blindness10.1
32hepatic encephalopathy10.0ASS1, SLC25A13
33propionic acidemia10.0ASS1, OTC
34hyperlysinemia10.0OTC, PC
35multiple carboxylase deficiency10.0PC, OTC
36brain edema10.0OTC, SLC25A13
37methylmalonic acidemia10.0PC, OTC
38biliary atresia10.0OTC, SLC25A13
39galactosemia10.0OTC, SLC25A13
40orotic aciduria10.0ASS1, OTC, ASL
41lysinuric protein intolerance10.0ASL, ASS1, OTC
42hypoglycemia10.0SLC25A13, PC
43brain disease10.0SLC25A13, PC, OTC
44status epilepticus10.0
45maple syrup urine disease10.0
46duodenitis10.0
47somatostatinoma10.0
48encephalitis10.0
49liver disease10.0
50neutropenia10.0

Graphical network of the top 20 diseases related to Citrullinemia:



Diseases related to citrullinemia

Symptoms for Citrullinemia

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48OMIM
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Symptoms by clinical synopsis from OMIM:

215700

Clinical features from OMIM:

215700

Drugs & Therapeutics for Citrullinemia

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Sources:
6CenterWatch, 43NIH Clinical Center, 7ClinicalTrials, 63UMLS, 42NDF-RT
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Approved drugs:

Search CenterWatch for Citrullinemia

Drug clinical trials:

Search ClinicalTrials for Citrullinemia

Search NIH Clinical Center for Citrullinemia

Search CenterWatch for Citrullinemia

Genetic Tests for Citrullinemia

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Anatomical Context for Citrullinemia

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34MalaCards
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MalaCards organs/tissues related to Citrullinemia:

34
Liver, Brain, Testes, Skin

Animal Models for Citrullinemia or affiliated genes

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38MGI
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MGI Mouse Phenotypes related to Citrullinemia:

38
idDescriptionMGI Source AccessionScoreTop Affiliating Genes
1MP:00053678.9OTC, SLC25A13, ASL

Publications for Citrullinemia

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Sources:
53PubMed
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Articles related to Citrullinemia:

(show top 50)    (show all 175)
idTitleAuthorsYear
1
Three cases of adult-onset type II citrullinemia treated with different therapies: Efficacy of sodium pyruvate and low-carbohydrate diet. (23701493)
2013
2
A 73-year-old patient with adult-onset type II citrullinemia successfully treated by sodium pyruvate and arginine. (23369404)
2013
3
An elderly Japanese patient with adult-onset type II citrullinemia with a novel D493G mutation in the SLC25A13 gene. (22892490)
2012
4
Molecular epidemiology of citrullinemia type I in a risk region of Argentina: a first step to preconception heterozygote detection. (23430935)
2012
5
Auxiliary partial orthotopic liver transplantation for adult onset type II citrullinemia. (22066084)
2011
6
Two hypomorphic alleles of mouse Ass1 as a new animal model of citrullinemia type I and other hyperammonemic syndromes. (20724589)
2010
7
A case of adult-onset type II citrullinemia with comorbid epilepsy even after liver transplantation. (21204812)
2010
8
Citrullinemia type I: molecular screening of the ASS1 gene by exonic sequencing and targeted mutation analysis. (20690080)
2010
9
A case of adult onset type II citrullinemia with portal-systemic shunt. (19285691)
2009
10
Possible mechanism for zonisamide-induced hyperammonemia in a child with citrullinemia type 1. (19584493)
2009
11
An adult with type 2 citrullinemia presenting in Europe. (18367750)
2008
12
Adult-onset citrullinemia]. (17228780)
2007
13
Homozygous SLC25A13 mutation in a Taiwanese patient with adult-onset citrullinemia complicated with steatosis and hepatocellular carcinoma. (17000460)
2006
14
Prenatal diagnosis of citrullinemia and argininosuccinic aciduria: evidence for a transmission ratio distortion in citrullinemia. (16475226)
2006
15
Citrulline and ammonia accumulating in citrullinemia reduces antioxidant capacity of rat brain in vitro. (16773471)
2006
16
Adult onset type II citrullinemia as a cause of non-alcoholic steatohepatitis. (16278034)
2006
17
Risk of worsened encephalopathy after intravenous glycerol therapy in patients with adult-onset type II citrullinemia (CTLN2). (15805705)
2005
18
Hyperammonemia with citrullinemia. (15347874)
2004
19
Adult-onset type II citrullinemia and idiopathic neonatal hepatitis caused by citrin deficiency: involvement of the aspartate glutamate carrier for urea synthesis and maintenance of the urea cycle. (15050970)
2004
20
Feasibility of auxiliary partial orthotopic liver transplantation from living donors for patients with adult-onset type II citrullinemia. (15048800)
2004
21
Effectiveness of carbohydrate-restricted diet and arginine granules therapy for adult-onset type II citrullinemia: a case report of siblings showing homozygous SLC25A13 mutation with and without the disease. (12787807)
2003
22
Structure of the human argininosuccinate synthetase gene and an improved system for molecular diagnostics in patients with classical and mild citrullinemia. (11941481)
2002
23
Infantile citrullinemia caused by citrin deficiency with increased dibasic amino acids. (12409267)
2002
24
Identification of two novel mutations in the SLC25A13 gene and detection of seven mutations in 102 patients with adult-onset type II citrullinemia. (11153906)
2000
25
Hepatocellular carcinoma associated with adult-type citrullinemia. (11215740)
2000
26
The first successful prenatal diagnosis on a Korean family with citrullinemia. (11211875)
2000
27
Complete neurological recovery of an adult patient with type II citrullinemia after living related partial liver transplantation. (8970629)
1996
28
Mutations in argininosuccinate synthetase mRNA in Japanese patients, causing classical citrullinemia. (7825601)
1995
29
Anesthetic management for a patient with citrullinemia and liver cirrhosis]. (7699832)
1995
30
Impaired ketogenesis in patients with adult-type citrullinemia. (7926463)
1994
31
Mutations in argininosuccinate synthetase mRNA of Japanese patients, causing classical citrullinemia. (7977368)
1994
32
Management of neonatal citrullinemia. (8292188)
1993
33
Citrullinemia and transposition of the great arteries. (8288339)
1993
34
Citrullinemia Type I (20301631)
1993
35
A search for the primary abnormality in adult-onset type II citrullinemia. (8105687)
1993
36
A case of citrullinemia associated with isolated ACTH deficiency, rapidly developing coma]. (1337025)
1992
37
Molecular basis of enzyme abnormalities in urea cycle disorders. With special reference to citrullinemia and argininosuccinic aciduria. (3440446)
1987
38
Increased urinary excretion of argininosuccinate in type II citrullinemia. (3436063)
1987
39
Structure of an abnormal messenger RNA for argininosuccinate synthetase in citrullinemia. (3570300)
1987
40
Pili torti in association with citrullinemia. (3973120)
1985
41
A case of transient neonatal citrullinemia. (6641770)
1983
42
Citrulline in amniotic fluid and the prenatal diagnosis of citrullinemia. (6844264)
1983
43
Citrullinemia: prenatal diagnosis of an affected fetus. (6823975)
1983
44
Diurnal fluctuation of blood ammonia levels in adult-type citrullinemia. (7202267)
1982
45
Variation in argininosuccinate synthetase activity in amniotic fluid cell cultures: implications for prenatal diagnosis of citrullinemia. (7318168)
1981
46
Lysine intolerance in a variant form of citrullinemia. (503639)
1979
47
Citrullinemia: enzymatic evidence for genetic heterogeneity. (1161343)
1975
48
Liver morphology in a case of citrullinemia (a light and electron microscopic study). (4829820)
1974
49
Citrullinemia. (5641790)
1968
50
Citrullinemia. A preliminary case report. (6015894)
1967

Variations for Citrullinemia

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Sources:
65UniProtKB/Swiss-Prot, 1 National Center for Biotechnology Information (Clinvar), 8dbSNP
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UniProtKB/Swiss-Prot genetic disease variations for Citrullinemia:

65 (show all 61)
id Symbol AA change Variation ID SNP ID
1ASS1p.Gly14SerVAR_000681
2ASS1p.Ser18LeuVAR_000682
3ASS1p.Arg86CysVAR_000683
4ASS1p.Ala118ThrVAR_000684
5ASS1p.Arg157HisVAR_000685
6ASS1p.Ser180AsnVAR_000686
7ASS1p.Ala192ValVAR_000687
8ASS1p.Arg272CysVAR_000688
9ASS1p.Gly280ArgVAR_000689
10ASS1p.Arg304TrpVAR_000690
11ASS1p.Gly324SerVAR_000691
12ASS1p.Arg363LeuVAR_000692
13ASS1p.Arg363TrpVAR_000693
14ASS1p.Gly390ArgVAR_000694
15ASS1p.Cys19ArgVAR_015891
16ASS1p.Arg86HisVAR_015892
17ASS1p.Arg95SerVAR_015893
18ASS1p.Pro96SerVAR_015894
19ASS1p.Gly117SerVAR_015895
20ASS1p.Gly117AspVAR_015896
21ASS1p.Arg157CysVAR_015897
22ASS1p.Trp179ArgVAR_015898rs121908646
23ASS1p.Glu191LysVAR_015899
24ASS1p.Arg265HisVAR_015900
25ASS1p.Val269MetVAR_015901
26ASS1p.Glu283LysVAR_015902
27ASS1p.Lys310ArgVAR_015903
28ASS1p.Gly362ValVAR_015904
29ASS1p.Glu270GlnVAR_016007
30ASS1p.Arg279GlnVAR_016008
31ASS1p.Lys310GlnVAR_016009
32ASS1p.Arg363GlyVAR_016010
33ASS1p.Arg363GlnVAR_016011
34ASS1p.Thr389IleVAR_016012
35ASS1p.Val69AlaVAR_016013
36ASS1p.Arg108LeuVAR_016014rs35269064
37ASS1p.Thr119IleVAR_016015
38ASS1p.Gln40LeuVAR_058337
39ASS1p.Ser79ProVAR_058338
40ASS1p.Pro96HisVAR_058339
41ASS1p.Asp124AsnVAR_058340
42ASS1p.Arg127GlnVAR_058341
43ASS1p.Arg127TrpVAR_058342
44ASS1p.Leu160ProVAR_058343
45ASS1p.Tyr190AspVAR_058344
46ASS1p.Glu191GlnVAR_058345
47ASS1p.Ala202GluVAR_058346
48ASS1p.Leu206ProVAR_058347
49ASS1p.Val263MetVAR_058348rs192838388
50ASS1p.Arg265CysVAR_058349
51ASS1p.Lys277ThrVAR_058350
52ASS1p.Thr284IleVAR_058351
53ASS1p.Tyr291SerVAR_058352
54ASS1p.Asp296GlyVAR_058353
55ASS1p.Met302ValVAR_058354
56ASS1p.Arg307CysVAR_058355rs183276875
57ASS1p.Gly324ValVAR_058356
58ASS1p.Ser341PheVAR_058357
59ASS1p.Val345GlyVAR_058358
60ASS1p.Gly347ArgVAR_058359
61ASS1p.Tyr359AspVAR_058360

Clinvar genetic disease variations for Citrullinemia:

1 (show all 17)
id Gene Name Type Significance SNP ID Assembly Location
1ASS1ASS1, EX5DELdeletionPathogenic
2ASS1ASS1, EX6DELdeletionPathogenic
3ASS1ASS1, IVS6AS, A-G, -2deletionPathogenic
4ASS1NM_000050.4(ASS1): c.40G> A (p.Gly14Ser)single nucleotide variantPathogenicrs121908636GRCh37Chr 9, 133327655: 133327655
5ASS1NM_000050.4(ASS1): c.470G> A (p.Arg157His)single nucleotide variantPathogenicrs121908637GRCh37Chr 9, 133342161: 133342161
6ASS1NM_000050.4(ASS1): c.539G> A (p.Ser180Asn)single nucleotide variantPathogenicrs121908638GRCh37Chr 9, 133346264: 133346264
7ASS1NM_000050.4(ASS1): c.970G> A (p.Gly324Ser)single nucleotide variantPathogenicrs121908639GRCh37Chr 9, 133364851: 133364851
8ASS1NM_000050.4(ASS1): c.1087C> T (p.Arg363Trp)single nucleotide variantPathogenicrs121908640GRCh37Chr 9, 133370370: 133370370
9ASS1NM_000050.4(ASS1): c.1168G> A (p.Gly390Arg)single nucleotide variantPathogenicrs121908641GRCh37Chr 9, 133374932: 133374932
10ASS1NM_000050.4(ASS1): c.910C> T (p.Arg304Trp)single nucleotide variantPathogenicrs121908642GRCh37Chr 9, 133364791: 133364791
11ASS1NM_000050.4(ASS1): c.53C> T (p.Ser18Leu)single nucleotide variantPathogenicrs121908643GRCh37Chr 9, 133327668: 133327668
12ASS1NM_000050.4(ASS1): c.256C> T (p.Arg86Cys)single nucleotide variantPathogenicrs121908644GRCh37Chr 9, 133333869: 133333869
13ASS1NM_000050.4(ASS1): c.835C> T (p.Arg279Ter)single nucleotide variantPathogenicrs121908645GRCh37Chr 9, 133355833: 133355833
14ASS1NM_000050.4(ASS1): c.323G> T (p.Arg108Leu)single nucleotide variantPathogenicrs35269064GRCh37Chr 9, 133333936: 133333936
15ASS1ASS1, IVS6, G-A, +5single nucleotide variantPathogenic
16ASS1ASS1, IVS15, G-C, -1single nucleotide variantPathogenic
17ASS1NM_000050.4(ASS1): c.928A> C (p.Lys310Gln)single nucleotide variantPathogenicrs121908648GRCh37Chr 9, 133364809: 133364809

Expression for genes affiliated with Citrullinemia

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Sources:
2BioGPS, 16Gene Expression Omnibus DataSets
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Expression patterns in normal tissues for genes affiliated with Citrullinemia

Search GEO for disease gene expression data for Citrullinemia.

Pathways for genes affiliated with Citrullinemia

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Sources:
51PathCards, 31KEGG, 56Reactome, 39NCBI BioSystems Database, 52PharmGKB
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Pathways related to Citrullinemia according to GeneCards/GeneDecks:

idSuper pathways (with members indented)ScoreTop Affiliating Genes
19.5ASL, ASS1
2
Show member pathways
malate-aspartate shuttle39
glycogen biosynthesis II (from UDP-D-Glucose)39
9.2SLC25A13, PC
3
Show member pathways
creatine-phosphate biosynthesis39
glycine degradation (creatine biosynthesis)39
putrescine biosynthesis III39
spermidine biosynthesis I39
tryptophan degradation via kynurenine39
spermine biosynthesis39
urea cycle39
S-methyl-5-thio-alpha-D-ribose 1-phosphate degradation I39
tyrosine degradation I39
L-carnitine biosynthesis39
methylthiopropionate biosynthesis39
2-oxoglutarate decarboxylation to succinyl-CoA39
S-methyl-5-thioadenosine degradation II39
8.9ASS1, ASL, OTC
4
Show member pathways
citrulline-nitric oxide cycle39
arginine degradation I (arginase pathway)39
proline degradation39
glutamine degradation I39
proline biosynthesis I39
superpathway of citrulline metabolism39
proline biosynthesis II (from arginine)39
citrulline biosynthesis39
arginine degradation VI (arginase 2 pathway)39
Urea cycle and metabolism of amino groups39
asparagine biosynthesis I39
4-hydroxyproline degradation I39
citrulline degradation39
8.9ASS1, ASL, OTC
5
Show member pathways
glutamate biosynthesis II39
arginine biosynthesis IV39
8.9OTC, ASL, ASS1
68.7ASS1, ASL, PC
7
Show member pathways
L-serine degradation39
pentose phosphate pathway (oxidative branch)39
formaldehyde oxidation II (glutathione-dependent)39
8.1OTC, PC, ASL, ASS1
8
Show member pathways
7.6OTC, SLC25A13, PC, ASL, ASS1

Compounds for genes affiliated with Citrullinemia

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Sources:
25HMDB, 12DrugBank, 46Novoseek, 30IUPHAR, 52PharmGKB, 3BitterDB
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Compounds related to Citrullinemia according to GeneCards/GeneDecks:

(show all 36)
idCompoundScoreTop Affiliating Genes
1Canavaninosuccinate259.9ASL, ASS1
2L-Aspartic acid25 1210.9SLC25A13, ASS1
3argininosuccinic acid46 2510.9ASS1, ASL
4guanidinoacetate469.9ASS1, ASL
5l-arginine30 25 1211.8ASL, ASS1
6sodium phenylbutyrate529.8OTC, ASS1
7delta(1)pyrroline-5-carboxylate469.8ASS1, OTC
8l-citrulline30 1210.8OTC, ASS1
9n-acetylglutamate469.7OTC, ASL
10allopurinol46 52 1211.6SLC22A7, OTC
11valproic acid46 52 25 1212.4SLC22A7, OTC
12sodium benzoate52 310.3OTC, ASL, ASS1
13ammonium469.3OTC, ASL, ASS1
14glucose 6-phosphate46 2510.3SLC22A7, PC
15carnitine469.2OTC, PC
16acyl-coa469.2PC, OTC
17creatinine469.1ASS1, ASL, OTC
18nadh46 25 1211.1SLC25A13, PC, ASS1
19phosphoenolpyruvate46 1210.0OTC, PC, ASS1
20pyruvate468.9OTC, PC, ASS1
21arginine468.9OTC, ASL, ASS1
22glycerol46 25 1210.9PC, SLC25A13, OTC
23malate468.9ASL, PC, OTC
24dexamethasone46 52 30 1211.8PC, ASL, ASS1
25citrate468.8PC, ASL
26nitric oxide46 25 1210.8ASS1, ASL, OTC
27fatty acid468.8OTC, SLC25A13, PC
28glutamine468.8ASL, PC, OTC
29atp46 309.6OTC, PC, ASS1
30phenylacetic acid52 46 2510.5ASS1, ASL, PC, OTC
31carbamoyl phosphate468.5OTC, PC, ASL, ASS1
32ornithine46 259.5ASS1, ASL, PC, OTC
33citrulline46 259.1OTC, SLC25A13, PC, ASL, ASS1
34urea46 25 1210.0ASS1, ASL, PC, SLC25A13, OTC
35aspartate468.0ASS1, ASL, PC, SLC25A13, OTC
36glutamate468.0ASS1, ASL, PC, SLC25A13, OTC

GO Terms for genes affiliated with Citrullinemia

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Sources:
17Gene Ontology
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Cellular components related to Citrullinemia according to GeneCards/GeneDecks:

idNameGO IDScoreTop Affiliating Genes
1mitochondrionGO:0057398.6OTC, SLC25A13, PC
2mitochondrial inner membraneGO:0057438.3OTC, SLC25A13, PC

Biological processes related to Citrullinemia according to GeneCards/GeneDecks:

idNameGO IDScoreTop Affiliating Genes
1arginine biosynthetic processGO:0065269.5OTC, ASS1
2glucose metabolic processGO:0060069.2SLC25A13, PC
3urea cycleGO:0000509.0OTC, ASL, ASS1
4gluconeogenesisGO:0060948.9SLC25A13, PC
5cellular nitrogen compound metabolic processGO:0346418.8OTC, ASL, ASS1
6small molecule metabolic processGO:0442817.6ASS1, ASL, PC, SLC25A13, OTC

Products for genes affiliated with Citrullinemia

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  • Antibodies
  • Proteins
  • Lysates
  • Antibodies

Sources for Citrullinemia

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4CDC
14ExPASy
15FMA
23GTR
24HGMD
25HMDB
26ICD10
27ICD10 via Orphanet
28ICD9CM
30IUPHAR
31KEGG
36MeSH
37MESH via Orphanet
38MGI
41NCIt
42NDF-RT
45NINDS
46Novoseek
48OMIM
49OMIM via Orphanet
53PubMed
54QIAGEN
60SNOMED-CT via Orphanet
63UMLS
64UMLS via Orphanet