CIT
MCID: CTR001
MIFTS: 57

Citrullinemia (CIT) malady

Genetic diseases, Metabolic diseases, Rare diseases categories
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Summaries for Citrullinemia

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Genetics Home Reference:21 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 based summary: Citrullinemia, also known as ass deficiency, is related to adult-onset citrullinemia type ii and citrin deficiency, and has symptoms including 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:8 An urea cycle disorder that involves the accumulation of ammonia in the blood.

Wikipedia:65 Citrullinemia is an autosomal recessive urea cycle disorder that causes ammonia and other toxic... more...

Description from OMIM:46 215700

Aliases & Classifications for Citrullinemia

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Sources:
8Disease Ontology, 9diseasecard, 21Genetics Home Reference, 46OMIM, 44Novoseek, 48Orphanet, 62UMLS, 57SNOMED-CT, 39NCIt, 34MeSH, 26ICD10 via Orphanet
See all sources

Citrullinemia, Aliases & Descriptions:

Name: Citrullinemia 8 9 21 46 44 62
Ass Deficiency 8 48 62
Argininosuccinic Acid Synthetase Deficiency 48 62
Deficiency of Citrulline-Aspartate Ligase 8 62
Argininosuccinate Synthetase Deficiency 48 62
Argininosuccinate Synthase Deficiency 48 62
Citrullinemia Type I 48 62
 
Citrullinemia Type 1 48 62
Citrullinuria 8 21
Ctln1 48 62
Argininosuccinic Acid Synthase Deficiency 48
Citrullinemia, Classic 62
Classic Citrullinemia 48
Cit 21


Classifications:



Characteristics (Orphanet epidemiological data):

48
ass deficiency:
Inheritance: Autosomal recessive; Prevalence: 1-9/100000; Age of onset: Variable


External Ids:

Disease Ontology8 DOID:9273
OMIM46 215700
NCIt39 C84639
MeSH34 D020159
ICD10 via Orphanet26 E72.2

Related Diseases for Citrullinemia

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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 82)
idRelated DiseaseScoreTop Affiliating Genes
1adult-onset citrullinemia type ii31.3ASS1, SLC25A13
2citrin deficiency30.9SLC25A13
3reye syndrome30.6OTC, PC
4argininosuccinic aciduria30.5ASL, OTC
5urea cycle disorder30.3ASL, ASS1
6carbamoyl phosphate synthetase i deficiency disease30.2OTC, ASS1
7hepatitis30.1ASL, OTC
8fatty liver disease29.9ASS1, PC, SLC25A13
9ornithine carbamoyltransferase deficiency29.9ASL, ASS1, OTC
10hyperargininemia29.9ASS1, ASL, OTC
11liver cirrhosis29.8SLC25A13, ASS1, OTC
12parkinson's disease10.7
13citrullinemia type i10.7
14tremor10.4
15dementia10.4
16neonatal intrahepatic cholestasis caused by citrin deficiency10.4
17essential tremor10.3
18acute neonatal citrullinemia type i10.3
19adult-onset citrullinemia type i10.3
20dystonia10.3
21pancreatitis10.3
22multiple system atrophy10.3
23hepatocellular carcinoma10.2
24progressive supranuclear palsy10.2
25meningioma10.2
26hepatic encephalopathy10.2ASS1, SLC25A13
27propionic acidemia10.1ASS1, OTC
28bipolar disorder10.1
29obsessive-compulsive disorder10.1
30cerebritis10.1
31blindness10.1
32hyperlysinemia10.1OTC, PC
33multiple carboxylase deficiency10.1PC, OTC
34brain edema10.1OTC, SLC25A13
35methylmalonic acidemia10.1PC, OTC
36biliary atresia10.0OTC, SLC25A13
37galactosemia10.0OTC, SLC25A13
38liver disease10.0
39neutropenia10.0
40schizophrenia10.0
41somatostatinoma10.0
42status epilepticus10.0
43hypertrophic pyloric stenosis10.0
44duodenitis10.0
45encephalitis10.0
46papilledema10.0
47pyloric stenosis10.0
48isolated acth deficiency10.0
49nonalcoholic steatohepatitis10.0
50pili torti10.0

Graphical network of the top 20 diseases related to Citrullinemia:



Diseases related to citrullinemia

Symptoms for Citrullinemia

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Symptoms by clinical synopsis from OMIM:

215700

Clinical features from OMIM:

215700

HPO human phenotypes related to Citrullinemia:

(show all 22)
id Description Frequency HPO Source Accession
1 stroke rare (5%) HP:0001297
2 autosomal recessive inheritance HP:0000007
3 irritability HP:0000737
4 intellectual disability HP:0001249
5 seizures HP:0001250
6 ataxia HP:0001251
7 lethargy HP:0001254
8 coma HP:0001259
9 global developmental delay HP:0001263
10 failure to thrive HP:0001508
11 respiratory alkalosis HP:0001950
12 episodic ammonia intoxication HP:0001951
13 hyperammonemia HP:0001987
14 vomiting HP:0002013
15 protein avoidance HP:0002038
16 cerebral edema HP:0002181
17 hepatomegaly HP:0002240
18 hyperglutaminemia HP:0003217
19 oroticaciduria HP:0003218
20 neonatal onset HP:0003623
21 phenotypic variability HP:0003812
22 hypoargininemia HP:0005961

Drugs & Therapeutics for Citrullinemia

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Drug clinical trials:

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Search NIH Clinical Center for Citrullinemia

Genetic Tests for Citrullinemia

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Anatomical Context for Citrullinemia

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MalaCards organs/tissues related to Citrullinemia:

32
Liver, Brain, Testes, Skin

Animal Models for Citrullinemia or affiliated genes

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MGI Mouse Phenotypes related to Citrullinemia:

36
idDescriptionMGI Source AccessionScoreTop Affiliating Genes
1MP:00053678.9OTC, SLC25A13, ASL

Publications for Citrullinemia

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Articles related to Citrullinemia:

(show top 50)    (show all 184)
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
Citrullinemia type I and hypertrophic pyloric stenosis in a 1-month old male infant. (24765495)
2013
3
A 73-year-old patient with adult-onset type II citrullinemia successfully treated by sodium pyruvate and arginine. (23369404)
2013
4
An elderly Japanese patient with adult-onset type II citrullinemia with a novel D493G mutation in the SLC25A13 gene. (22892490)
2012
5
Molecular epidemiology of citrullinemia type I in a risk region of Argentina: a first step to preconception heterozygote detection. (23430935)
2012
6
Auxiliary partial orthotopic liver transplantation for adult onset type II citrullinemia. (22066084)
2011
7
Two hypomorphic alleles of mouse Ass1 as a new animal model of citrullinemia type I and other hyperammonemic syndromes. (20724589)
2010
8
A case of adult-onset type II citrullinemia with comorbid epilepsy even after liver transplantation. (21204812)
2010
9
Citrullinemia type I: molecular screening of the ASS1 gene by exonic sequencing and targeted mutation analysis. (20690080)
2010
10
A case of adult onset type II citrullinemia with portal-systemic shunt. (19285691)
2009
11
Possible mechanism for zonisamide-induced hyperammonemia in a child with citrullinemia type 1. (19584493)
2009
12
An adult with type 2 citrullinemia presenting in Europe. (18367750)
2008
13
Adult-onset citrullinemia]. (17228780)
2007
14
Homozygous SLC25A13 mutation in a Taiwanese patient with adult-onset citrullinemia complicated with steatosis and hepatocellular carcinoma. (17000460)
2006
15
Prenatal diagnosis of citrullinemia and argininosuccinic aciduria: evidence for a transmission ratio distortion in citrullinemia. (16475226)
2006
16
Citrulline and ammonia accumulating in citrullinemia reduces antioxidant capacity of rat brain in vitro. (16773471)
2006
17
Adult onset type II citrullinemia as a cause of non-alcoholic steatohepatitis. (16278034)
2006
18
Risk of worsened encephalopathy after intravenous glycerol therapy in patients with adult-onset type II citrullinemia (CTLN2). (15805705)
2005
19
Hyperammonemia with citrullinemia. (15347874)
2004
20
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
21
Feasibility of auxiliary partial orthotopic liver transplantation from living donors for patients with adult-onset type II citrullinemia. (15048800)
2004
22
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
23
Structure of the human argininosuccinate synthetase gene and an improved system for molecular diagnostics in patients with classical and mild citrullinemia. (11941481)
2002
24
Infantile citrullinemia caused by citrin deficiency with increased dibasic amino acids. (12409267)
2002
25
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
26
Hepatocellular carcinoma associated with adult-type citrullinemia. (11215740)
2000
27
The first successful prenatal diagnosis on a Korean family with citrullinemia. (11211875)
2000
28
Complete neurological recovery of an adult patient with type II citrullinemia after living related partial liver transplantation. (8970629)
1996
29
Mutations in argininosuccinate synthetase mRNA in Japanese patients, causing classical citrullinemia. (7825601)
1995
30
Anesthetic management for a patient with citrullinemia and liver cirrhosis]. (7699832)
1995
31
Impaired ketogenesis in patients with adult-type citrullinemia. (7926463)
1994
32
Mutations in argininosuccinate synthetase mRNA of Japanese patients, causing classical citrullinemia. (7977368)
1994
33
Management of neonatal citrullinemia. (8292188)
1993
34
Citrullinemia and transposition of the great arteries. (8288339)
1993
35
Citrullinemia Type I (20301631)
1993
36
A search for the primary abnormality in adult-onset type II citrullinemia. (8105687)
1993
37
A case of citrullinemia associated with isolated ACTH deficiency, rapidly developing coma]. (1337025)
1992
38
Molecular basis of enzyme abnormalities in urea cycle disorders. With special reference to citrullinemia and argininosuccinic aciduria. (3440446)
1987
39
Increased urinary excretion of argininosuccinate in type II citrullinemia. (3436063)
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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UniProtKB/Swiss-Prot genetic disease variations for Citrullinemia:

64 (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:

6 (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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Expression patterns in normal tissues for genes affiliated with Citrullinemia

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Pathways for genes affiliated with Citrullinemia

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Pathways related to Citrullinemia according to GeneCards/GeneDecks:

idSuper pathways (with members indented)ScoreTop Affiliating Genes
19.5ASS1, ASL
2
Show member pathways
malate-aspartate shuttle37
glycogen biosynthesis II (from UDP-D-Glucose)37
9.2PC, SLC25A13
3
Show member pathways
glutamate biosynthesis II37
arginine biosynthesis IV37
8.9ASL, ASS1, OTC
4
Show member pathways
creatine-phosphate biosynthesis37
glycine degradation (creatine biosynthesis)37
putrescine biosynthesis III37
spermidine biosynthesis I37
tryptophan degradation via kynurenine37
spermine biosynthesis37
urea cycle37
S-methyl-5-thio-alpha-D-ribose 1-phosphate degradation I37
tyrosine degradation I37
L-carnitine biosynthesis37
methylthiopropionate biosynthesis37
2-oxoglutarate decarboxylation to succinyl-CoA37
S-methyl-5-thioadenosine degradation II37
8.9OTC, ASL, ASS1
5
Show member pathways
citrulline-nitric oxide cycle37
arginine degradation I (arginase pathway)37
proline degradation37
glutamine degradation I37
proline biosynthesis I37
superpathway of citrulline metabolism37
proline biosynthesis II (from arginine)37
citrulline biosynthesis37
arginine degradation VI (arginase 2 pathway)37
Urea cycle and metabolism of amino groups37
asparagine biosynthesis I37
4-hydroxyproline degradation I37
citrulline degradation37
8.9ASL, OTC, ASS1
68.7PC, ASL, ASS1
7
Show member pathways
L-serine degradation37
pentose phosphate pathway (oxidative branch)37
formaldehyde oxidation II (glutathione-dependent)37
8.1OTC, PC, ASS1, ASL
8
Show member pathways
7.6ASS1, ASL, OTC, SLC25A13, PC

Compounds for genes affiliated with Citrullinemia

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Sources:
24HMDB, 11DrugBank, 44Novoseek, 28IUPHAR, 50PharmGKB, 2BitterDB
See all sources

Compounds related to Citrullinemia according to GeneCards/GeneDecks:

(show all 36)
idCompoundScoreTop Affiliating Genes
1Canavaninosuccinate249.9ASL, ASS1
2L-Aspartic acid24 1110.9SLC25A13, ASS1
3argininosuccinic acid44 2410.9ASS1, ASL
4guanidinoacetate449.9ASS1, ASL
5l-arginine28 24 1111.8ASL, ASS1
6sodium phenylbutyrate509.8OTC, ASS1
7delta(1)pyrroline-5-carboxylate449.8ASS1, OTC
8l-citrulline28 1110.8OTC, ASS1
9n-acetylglutamate449.7OTC, ASL
10allopurinol44 50 1111.6SLC22A7, OTC
11valproic acid44 50 24 1112.4SLC22A7, OTC
12sodium benzoate50 210.3OTC, ASL, ASS1
13ammonium449.3OTC, ASL, ASS1
14glucose 6-phosphate44 2410.3SLC22A7, PC
15carnitine449.2OTC, PC
16acyl-coa449.2PC, OTC
17creatinine449.1ASS1, ASL, OTC
18nadh44 24 1111.1SLC25A13, PC, ASS1
19phosphoenolpyruvate44 1110.0OTC, PC, ASS1
20pyruvate448.9OTC, PC, ASS1
21arginine448.9OTC, ASL, ASS1
22glycerol44 24 1110.9PC, SLC25A13, OTC
23malate448.9ASL, PC, OTC
24dexamethasone44 50 28 1111.8PC, ASL, ASS1
25citrate448.8PC, ASL
26nitric oxide44 24 1110.8ASS1, ASL, OTC
27fatty acid448.8OTC, SLC25A13, PC
28glutamine448.8ASL, PC, OTC
29atp44 289.6OTC, PC, ASS1
30phenylacetic acid50 44 2410.5ASS1, ASL, PC, OTC
31carbamoyl phosphate448.5OTC, PC, ASL, ASS1
32ornithine44 249.5ASS1, ASL, PC, OTC
33citrulline44 249.1OTC, SLC25A13, PC, ASL, ASS1
34urea44 24 1110.0ASS1, ASL, PC, SLC25A13, OTC
35aspartate448.0ASS1, ASL, PC, SLC25A13, OTC
36glutamate448.0ASS1, ASL, PC, SLC25A13, OTC

GO Terms for genes affiliated with Citrullinemia

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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
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  • Lysates

Sources for Citrullinemia

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3CDC
13ExPASy
14FMA
22GTR
23HGMD
24HMDB
25ICD10
26ICD10 via Orphanet
27ICD9CM
28IUPHAR
29KEGG
34MeSH
35MESH via Orphanet
36MGI
39NCIt
40NDF-RT
43NINDS
44Novoseek
46OMIM
47OMIM via Orphanet
51PubMed
52QIAGEN
58SNOMED-CT via Orphanet
62UMLS
63UMLS via Orphanet