MCID: CTR077
MIFTS: 29

Citrullinemia, Type Ii, Neonatal-Onset

Categories: Genetic diseases, Rare diseases, Metabolic diseases

Aliases & Classifications for Citrullinemia, Type Ii, Neonatal-Onset

MalaCards integrated aliases for Citrullinemia, Type Ii, Neonatal-Onset:

Name: Citrullinemia, Type Ii, Neonatal-Onset 57 75 13 73
Neonatal Intrahepatic Cholestasis Caused by Citrin Deficiency 53 59 29 6
Niccd 57 53 59 75
Citrin Deficiency 53 75 73
Citrullinemia, Type Ii, Neonatal-Onset, with or Without Failure to Thrive and Dyslipidemia 57 75
Cholestasis, Neonatal Intrahepatic, Caused by Citrin Deficiency 57 75
Neonatal-Onset Citrullinemia Type Ii 53 75
Neonatal-Onset Citrullinemia Type 2 53 75
Cholestasis, Neonatal Intrahepatic, Caused by Citrin Deficiency; Niccd 57
Neonatal Intrahepatic Cholestasis Due to Citrin Deficiency 59
Citrullinemia, Type Ii, Neonatal-Onset ) 40
Adult-Onset Citrullinemia Type 2 73

Characteristics:

Orphanet epidemiological data:

59
neonatal intrahepatic cholestasis due to citrin deficiency
Inheritance: Autosomal recessive; Age of onset: Infancy,Neonatal;

OMIM:

57
Inheritance:
autosomal recessive

Miscellaneous:
most have resolution of symptoms between 6 and 12 months
some patients may develop concurrent failure to thrive and dyslipidemia
natural aversion to carbohydrates and favoring of protein


HPO:

32
citrullinemia, type ii, neonatal-onset:
Inheritance autosomal recessive inheritance


Classifications:

Orphanet: 59  
Inborn errors of metabolism


External Ids:

OMIM 57 605814
Orphanet 59 ORPHA247598
UMLS via Orphanet 74 C1853942
ICD10 via Orphanet 34 E72.2
MedGen 42 C1853942
MeSH 44 D002780

Summaries for Citrullinemia, Type Ii, Neonatal-Onset

NIH Rare Diseases : 53 Neonatal intrahepatic cholestasis caused by citrin deficiency (NICCD) is a 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. This leads to transient intrahepatic cholestasis and variable liver dysfunction in children younger than one year of age. NICCD is generally not severe, and symptoms disappear by age one year with appropriate treatment. Years or even decades later, however, some of these individuals develop the characteristic features of adult-onset type II citrullinemia. NICCD is caused by mutations in the SLC25A13 gene. This condition is inherited in an autosomal recessive pattern.

MalaCards based summary : Citrullinemia, Type Ii, Neonatal-Onset, also known as neonatal intrahepatic cholestasis caused by citrin deficiency, is related to citrullinemia, type ii, adult-onset and cholestasis. An important gene associated with Citrullinemia, Type Ii, Neonatal-Onset is SLC25A13 (Solute Carrier Family 25 Member 13). Affiliated tissues include liver, and related phenotypes are cirrhosis and intrahepatic cholestasis

OMIM : 57 Neonatal intrahepatic cholestasis caused by citrin deficiency (NICCD) is an autosomal recessive metabolic disorder characterized by poor growth, intrahepatic cholestasis, and increased serum citrulline. Most patients show spontaneous improvement by 1 year of age. However, some patients may have a progressive course with continued failure to thrive and dyslipidemia caused by citrin deficiency (FTTDCD), and some may develop chronic or fatal liver disease (summary by Song et al., 2011). (605814)

UniProtKB/Swiss-Prot : 75 Cholestasis, neonatal intrahepatic, caused by citrin deficiency: A form of citrullinemia type 2 with neonatal onset, characterized by suppression of the bile flow, hepatic fibrosis, low birth weight, growth retardation, hypoproteinemia, variable liver dysfunction. Neonatal intrahepatic cholestasis due to citrin deficiency is generally not severe and symptoms disappear by one year of age with an appropriate diet. Years or even decades later, however, some individuals develop the characteristic features of citrullinemia type 2 with neuropsychiatric symptoms.

Related Diseases for Citrullinemia, Type Ii, Neonatal-Onset

Diseases in the Citrullinemia, Type Ii, Neonatal-Onset family:

Acute Neonatal Citrullinemia Type I

Diseases related to Citrullinemia, Type Ii, Neonatal-Onset via text searches within MalaCards or GeneCards Suite gene sharing:

# Related Disease Score Top Affiliating Genes
1 citrullinemia, type ii, adult-onset 11.5
2 cholestasis 10.3
3 intrahepatic cholestasis 10.3
4 hepatitis 10.0
5 fatty liver disease, nonalcoholic 1 9.9
6 liver disease 9.9

Graphical network of the top 20 diseases related to Citrullinemia, Type Ii, Neonatal-Onset:



Diseases related to Citrullinemia, Type Ii, Neonatal-Onset

Symptoms & Phenotypes for Citrullinemia, Type Ii, Neonatal-Onset

Symptoms via clinical synopsis from OMIM:

57
Growth Other:
failure to thrive
poor growth

Laboratory Abnormalities:
increased serum triglycerides
decreased hdl cholesterol
increased cholesterol
elevated bilirubin (bilirubinemia)
elevated plasma citrulline (citrullinemia)
more
Abdomen Liver:
cirrhosis
intrahepatic cholestasis
elevated bilirubin (bilirubinemia)

Hematology:
echinocytosis


Clinical features from OMIM:

605814

Human phenotypes related to Citrullinemia, Type Ii, Neonatal-Onset:

32 (show all 10)
# Description HPO Frequency HPO Source Accession
1 cirrhosis 32 HP:0001394
2 intrahepatic cholestasis 32 HP:0001406
3 failure to thrive 32 HP:0001508
4 growth delay 32 HP:0001510
5 hypertriglyceridemia 32 HP:0002155
6 hyperbilirubinemia 32 HP:0002904
7 hypercholesterolemia 32 HP:0003124
8 decreased hdl cholesterol concentration 32 HP:0003233
9 hypermethioninemia 32 HP:0003235
10 elevated plasma citrulline 32 HP:0011966

Drugs & Therapeutics for Citrullinemia, Type Ii, Neonatal-Onset

Search Clinical Trials , NIH Clinical Center for Citrullinemia, Type Ii, Neonatal-Onset

Genetic Tests for Citrullinemia, Type Ii, Neonatal-Onset

Genetic tests related to Citrullinemia, Type Ii, Neonatal-Onset:

# Genetic test Affiliating Genes
1 Neonatal Intrahepatic Cholestasis Caused by Citrin Deficiency 29 SLC25A13

Anatomical Context for Citrullinemia, Type Ii, Neonatal-Onset

MalaCards organs/tissues related to Citrullinemia, Type Ii, Neonatal-Onset:

41
Liver

Publications for Citrullinemia, Type Ii, Neonatal-Onset

Articles related to Citrullinemia, Type Ii, Neonatal-Onset:

(show all 29)
# Title Authors Year
1
Analysis of islet beta cell functions and their correlations with liver dysfunction in patients with neonatal intrahepatic cholestasis caused by citrin deficiency (NICCD). ( 29137101 )
2017
2
Identification of a Large SLC25A13 Deletion via Sophisticated Molecular Analyses Using Peripheral Blood Lymphocytes in an Infant with Neonatal Intrahepatic Cholestasis Caused by Citrin Deficiency (NICCD): A Clinical and Molecular Study. ( 27127784 )
2016
3
SLC25A13 cDNA cloning analysis using peripheral blood lymphocytes facilitates the identification of a large deletion mutation: Molecular diagnosis of an infant with neonatal intrahepatic cholestasis caused by citrin deficiency. ( 27779681 )
2016
4
Clinical, molecular and functional investigation on an infant with neonatal intrahepatic cholestasis caused by citrin deficiency (NICCD). ( 24586645 )
2014
5
[Utilization of high-resolution melting analysis to screen patients with neonatal intrahepatic cholestasis caused by citrin deficiency]. ( 22487826 )
2012
6
Multiple ovarian antral follicles in a preterm infant with neonatal intrahepatic cholestasis caused by citrin deficiency: a clinical, genetic and transcriptional analysis. ( 22710133 )
2012
7
Neonatal intrahepatic cholestasis caused by citrin deficiency: prevalence and SLC25A13 mutations among Thai infants. ( 23067347 )
2012
8
Treatment with lactose (galactose)-restricted and medium-chain triglyceride-supplemented formula for neonatal intrahepatic cholestasis caused by citrin deficiency. ( 23430852 )
2012
9
Diagnosis of neonatal intrahepatic cholestasis caused by citrin deficiency using high-resolution melting analysis and a clinical scoring system. ( 22575253 )
2012
10
A new Caucasian case of neonatal intrahepatic cholestasis caused by citrin deficiency (NICCD): a clinical, molecular, and functional study. ( 21914561 )
2011
11
Neonatal intrahepatic cholestasis caused by citrin deficiency in two Malaysian siblings: outcome at one year of life. ( 20200759 )
2010
12
[Studies on the clinical manifestation and SLC25A13 gene mutation of Chinese patients with neonatal intrahepatic cholestasis caused by citrin deficiency]. ( 20376801 )
2010
13
Neonatal intrahepatic cholestasis caused by citrin deficiency (NICCD) in three Malay children. ( 20614727 )
2010
14
Histological findings in the livers of patients with neonatal intrahepatic cholestasis caused by citrin deficiency. ( 20070398 )
2010
15
Liver transplantation for an infant with neonatal intrahepatic cholestasis caused by citrin deficiency using heterozygote living donor. ( 19413723 )
2010
16
Neonatal intrahepatic cholestasis caused by citrin deficiency: clinical and laboratory investigation of 13 subjects in mainland of China. ( 19185551 )
2009
17
Neonatal intrahepatic cholestasis caused by citrin deficiency (NICCD) as a cause of liver disease in infants in the UK. ( 19517266 )
2009
18
[Identification and diagnosis of three novel mutations in SLC25A13 gene of neonatal intrahepatic cholestasis caused by citrin deficiency]. ( 19099775 )
2008
19
Chubby face and the biochemical parameters for the early diagnosis of neonatal intrahepatic cholestasis caused by citrin deficiency. ( 18664871 )
2008
20
Clinical pictures of 75 patients with neonatal intrahepatic cholestasis caused by citrin deficiency (NICCD). ( 17323144 )
2007
21
Neonatal intrahepatic cholestasis caused by citrin deficiency in Korean infants. ( 18162705 )
2007
22
[SLC25A13 gene mutation analysis in a pedigree of neonatal intrahepatic cholestasis caused by citrin deficiency]. ( 17880783 )
2007
23
Hepatic steatosis and neonatal intrahepatic cholestasis caused by citrin deficiency (NICCD) in Taiwanese infants. ( 16737877 )
2006
24
Time course of acylcarnitine elevation in neonatal intrahepatic cholestasis caused by citrin deficiency. ( 16736097 )
2006
25
[A difficult and complicated case study: neonatal intrahepatic cholestasis caused by citrin deficiency]. ( 16613706 )
2006
26
A possible mechanism of neonatal intrahepatic cholestasis caused by citrin deficiency. ( 15777702 )
2005
27
Clinical heterogeneity of neonatal intrahepatic cholestasis caused by citrin deficiency: case reports from 16 patients. ( 15542392 )
2004
28
A novel inborn error of metabolism detected by elevated methionine and/or galactose in newborn screening: neonatal intrahepatic cholestasis caused by citrin deficiency. ( 12692712 )
2003
29
Neonatal intrahepatic cholestasis caused by citrin deficiency: severe hepatic dysfunction in an infant requiring liver transplantation. ( 12424587 )
2002

Variations for Citrullinemia, Type Ii, Neonatal-Onset

UniProtKB/Swiss-Prot genetic disease variations for Citrullinemia, Type Ii, Neonatal-Onset:

75
# Symbol AA change Variation ID SNP ID
1 SLC25A13 p.Glu601Lys VAR_016601 rs80338727

ClinVar genetic disease variations for Citrullinemia, Type Ii, Neonatal-Onset:

6
(show all 39)
# Gene Variation Type Significance SNP ID Assembly Location
1 SLC25A13 NM_014251.2(SLC25A13): c.1177+1G> A single nucleotide variant Pathogenic rs80338722 GRCh37 Chromosome 7, 95813588: 95813588
2 SLC25A13 NM_014251.2(SLC25A13): c.1177+1G> A single nucleotide variant Pathogenic rs80338722 GRCh38 Chromosome 7, 96184276: 96184276
3 SLC25A13 NM_014251.2(SLC25A13): c.1799dupA (p.Tyr600Terfs) duplication Pathogenic rs80338726 GRCh37 Chromosome 7, 95751009: 95751009
4 SLC25A13 NM_014251.2(SLC25A13): c.1799dupA (p.Tyr600Terfs) duplication Pathogenic rs80338726 GRCh38 Chromosome 7, 96121697: 96121697
5 SLC25A13 NM_014251.2(SLC25A13): c.1078C> T (p.Arg360Ter) single nucleotide variant Pathogenic rs80338721 GRCh37 Chromosome 7, 95813688: 95813688
6 SLC25A13 NM_014251.2(SLC25A13): c.1078C> T (p.Arg360Ter) single nucleotide variant Pathogenic rs80338721 GRCh38 Chromosome 7, 96184376: 96184376
7 SLC25A13 NM_014251.2(SLC25A13): c.1592G> A (p.Gly531Asp) single nucleotide variant Pathogenic rs80338724 GRCh37 Chromosome 7, 95751309: 95751309
8 SLC25A13 NM_014251.2(SLC25A13): c.1592G> A (p.Gly531Asp) single nucleotide variant Pathogenic rs80338724 GRCh38 Chromosome 7, 96121997: 96121997
9 SLC25A13 NM_014251.2(SLC25A13): c.15G> A (p.Lys5=) single nucleotide variant Pathogenic rs80338715 GRCh37 Chromosome 7, 95951254: 95951254
10 SLC25A13 NM_014251.2(SLC25A13): c.15G> A (p.Lys5=) single nucleotide variant Pathogenic rs80338715 GRCh38 Chromosome 7, 96321942: 96321942
11 SLC25A13 NM_014251.2(SLC25A13): c.1750_1751[insNM_138459.3: 2672_24;1750+72_1751-4dup] complex Pathogenic
12 SLC25A13 NM_014251.2(SLC25A13): c.1801G> A (p.Glu601Lys) single nucleotide variant Pathogenic rs80338727 GRCh37 Chromosome 7, 95751007: 95751007
13 SLC25A13 NM_014251.2(SLC25A13): c.1801G> A (p.Glu601Lys) single nucleotide variant Pathogenic rs80338727 GRCh38 Chromosome 7, 96121695: 96121695
14 SLC25A13 NM_014251.2(SLC25A13): c.1801G> T (p.Glu601Ter) single nucleotide variant Pathogenic rs80338727 GRCh37 Chromosome 7, 95751007: 95751007
15 SLC25A13 NM_014251.2(SLC25A13): c.1801G> T (p.Glu601Ter) single nucleotide variant Pathogenic rs80338727 GRCh38 Chromosome 7, 96121695: 96121695
16 SLC25A13 NM_014251.2(SLC25A13): c.1813C> T (p.Arg605Ter) single nucleotide variant Pathogenic rs80338729 GRCh37 Chromosome 7, 95750995: 95750995
17 SLC25A13 NM_014251.2(SLC25A13): c.1813C> T (p.Arg605Ter) single nucleotide variant Pathogenic rs80338729 GRCh38 Chromosome 7, 96121683: 96121683
18 SLC25A13 NM_014251.2(SLC25A13): c.550C> T (p.Arg184Ter) single nucleotide variant Pathogenic rs80338716 GRCh37 Chromosome 7, 95822414: 95822414
19 SLC25A13 NM_014251.2(SLC25A13): c.550C> T (p.Arg184Ter) single nucleotide variant Pathogenic rs80338716 GRCh38 Chromosome 7, 96193102: 96193102
20 SLC25A13 NM_014251.2(SLC25A13): c.615+1G> C single nucleotide variant Pathogenic rs80338718 GRCh37 Chromosome 7, 95822348: 95822348
21 SLC25A13 NM_014251.2(SLC25A13): c.615+1G> C single nucleotide variant Pathogenic rs80338718 GRCh38 Chromosome 7, 96193036: 96193036
22 SLC25A13 NM_014251.2(SLC25A13): c.615+5G> A single nucleotide variant Pathogenic rs80338717 GRCh37 Chromosome 7, 95822344: 95822344
23 SLC25A13 NM_014251.2(SLC25A13): c.615+5G> A single nucleotide variant Pathogenic rs80338717 GRCh38 Chromosome 7, 96193032: 96193032
24 SLC25A13 NM_014251.2(SLC25A13): c.852_855delTATG (p.Met285Profs) deletion Pathogenic rs80338720 GRCh37 Chromosome 7, 95818684: 95818687
25 SLC25A13 NM_014251.2(SLC25A13): c.852_855delTATG (p.Met285Profs) deletion Pathogenic rs80338720 GRCh38 Chromosome 7, 96189372: 96189375
26 SLC25A13 NM_014251.2(SLC25A13): c.1958A> G (p.Lys653Arg) single nucleotide variant Uncertain significance rs879255501 GRCh38 Chromosome 7, 96121261: 96121261
27 SLC25A13 NM_014251.2(SLC25A13): c.1958A> G (p.Lys653Arg) single nucleotide variant Uncertain significance rs879255501 GRCh37 Chromosome 7, 95750573: 95750573
28 SLC25A13 NM_014251.2(SLC25A13): c.1505C> T (p.Pro502Leu) single nucleotide variant Uncertain significance rs139149160 GRCh38 Chromosome 7, 96131829: 96131829
29 SLC25A13 NM_014251.2(SLC25A13): c.1505C> T (p.Pro502Leu) single nucleotide variant Uncertain significance rs139149160 GRCh37 Chromosome 7, 95761141: 95761141
30 SLC25A13 NM_014251.2(SLC25A13): c.1311C> T (p.Cys437=) single nucleotide variant Uncertain significance rs879255502 GRCh38 Chromosome 7, 96170045: 96170045
31 SLC25A13 NM_014251.2(SLC25A13): c.1311C> T (p.Cys437=) single nucleotide variant Uncertain significance rs879255502 GRCh37 Chromosome 7, 95799357: 95799357
32 SLC25A13 NM_014251.2(SLC25A13): c.775C> T (p.Gln259Ter) single nucleotide variant Pathogenic rs746155190 GRCh38 Chromosome 7, 96189654: 96189654
33 SLC25A13 NM_014251.2(SLC25A13): c.775C> T (p.Gln259Ter) single nucleotide variant Pathogenic rs746155190 GRCh37 Chromosome 7, 95818966: 95818966
34 SLC25A13 NM_014251.2(SLC25A13): c.616-11A> G single nucleotide variant Uncertain significance rs879255503 GRCh38 Chromosome 7, 96191258: 96191258
35 SLC25A13 NM_014251.2(SLC25A13): c.616-11A> G single nucleotide variant Uncertain significance rs879255503 GRCh37 Chromosome 7, 95820570: 95820570
36 SLC25A13 NM_014251.2(SLC25A13): c.495delA (p.Ala166Profs) deletion Pathogenic rs879255504 GRCh38 Chromosome 7, 96193157: 96193157
37 SLC25A13 NM_014251.2(SLC25A13): c.495delA (p.Ala166Profs) deletion Pathogenic rs879255504 GRCh37 Chromosome 7, 95822469: 95822469
38 SLC25A13 NM_014251.2(SLC25A13): c.468+1G> C single nucleotide variant Likely pathogenic rs1060499612 GRCh38 Chromosome 7, 96208837: 96208837
39 SLC25A13 NM_014251.2(SLC25A13): c.468+1G> C single nucleotide variant Likely pathogenic rs1060499612 GRCh37 Chromosome 7, 95838149: 95838149

Expression for Citrullinemia, Type Ii, Neonatal-Onset

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GO Terms for Citrullinemia, Type Ii, Neonatal-Onset

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