MCID: CTR077
MIFTS: 31

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 53 71 13 69
Niccd 53 49 55 71
Neonatal Intrahepatic Cholestasis Caused by Citrin Deficiency 49 55 28
Citrin Deficiency 49 71 69
Citrullinemia, Type Ii, Neonatal-Onset, with or Without Failure to Thrive and Dyslipidemia 53 71
Cholestasis, Neonatal Intrahepatic, Caused by Citrin Deficiency 53 71
Neonatal-Onset Citrullinemia Type Ii 49 71
Neonatal-Onset Citrullinemia Type 2 49 71
Cholestasis, Neonatal Intrahepatic, Caused by Citrin Deficiency; Niccd 53
Neonatal Intrahepatic Cholestasis Due to Citrin Deficiency 55
Adult-Onset Citrullinemia Type 2 69

Characteristics:

Orphanet epidemiological data:

55
neonatal intrahepatic cholestasis due to citrin deficiency
Inheritance: Autosomal recessive; Age of onset: Infancy,Neonatal;

OMIM:

53
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:

31
citrullinemia, type ii, neonatal-onset:
Inheritance autosomal recessive inheritance


Classifications:

Orphanet: 55  
Inborn errors of metabolism


External Ids:

OMIM 53 605814
Orphanet 55 ORPHA247598
UMLS via Orphanet 70 C1853942
ICD10 via Orphanet 33 E72.2
MedGen 39 C1853942
MeSH 41 D002780

Summaries for Citrullinemia, Type Ii, Neonatal-Onset

NIH Rare Diseases : 49 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. Last updated: 7/11/2011

MalaCards based summary : Citrullinemia, Type Ii, Neonatal-Onset, also known as niccd, is related to citrullinemia, type ii, adult-onset and cholestasis, and has symptoms including failure to thrive, hypertriglyceridemia and growth delay. An important gene associated with Citrullinemia, Type Ii, Neonatal-Onset is SLC25A13 (Solute Carrier Family 25 Member 13). Affiliated tissues include liver.

OMIM : 53 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 : 71 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:

(show all 16)
# Related Disease Score Top Affiliating Genes
1 citrullinemia, type ii, adult-onset 12.1
2 cholestasis 10.6
3 intrahepatic cholestasis 10.6
4 hepatitis 10.2
5 citrullinemia, classic 10.1
6 liver disease 10.1
7 blood group, i system 10.0
8 encephalopathy 10.0
9 galactosemia 9.8
10 phenylketonuria 9.8
11 fatty liver disease, nonalcoholic 1 9.8
12 carbonic anhydrase va deficiency, hyperammonemia due to 9.8
13 hepatic encephalopathy 9.8
14 fatty liver disease 9.8
15 classic galactosemia and clinical variant galactosemia 9.8
16 benign idiopathic neonatal seizures 9.8

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:

53
GrowthOther:
failure to thrive
poor growth

LaboratoryAbnormalities:
increased serum triglycerides
decreased hdl cholesterol
increased cholesterol
elevated bilirubin (bilirubinemia)
elevated plasma citrulline (citrullinemia)
more
AbdomenLiver:
cirrhosis
intrahepatic cholestasis
elevated bilirubin (bilirubinemia)

Hematology:
echinocytosis


Clinical features from OMIM:

605814

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

31 (show all 10)
# Description HPO Frequency HPO Source Accession
1 failure to thrive 31 HP:0001508
2 hypertriglyceridemia 31 HP:0002155
3 growth delay 31 HP:0001510
4 cirrhosis 31 HP:0001394
5 hypercholesterolemia 31 HP:0003124
6 hyperbilirubinemia 31 HP:0002904
7 intrahepatic cholestasis 31 HP:0001406
8 hypermethioninemia 31 HP:0003235
9 decreased circulating high-density lipoprotein levels 31 HP:0003233
10 elevated plasma citrulline 31 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 28 SLC25A13

Anatomical Context for Citrullinemia, Type Ii, Neonatal-Onset

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

38
Liver

Publications for Citrullinemia, Type Ii, Neonatal-Onset

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

(show all 31)
# 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
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
3
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
4
Clinical, molecular and functional investigation on an infant with neonatal intrahepatic cholestasis caused by citrin deficiency (NICCD). ( 24586645 )
2014
5
Diagnosis of neonatal intrahepatic cholestasis caused by citrin deficiency using high-resolution melting analysis and a clinical scoring system. ( 22575253 )
2012
6
Neonatal intrahepatic cholestasis caused by citrin deficiency: prevalence and SLC25A13 mutations among Thai infants. ( 23067347 )
2012
7
Multiple ovarian antral follicles in a preterm infant with neonatal intrahepatic cholestasis caused by citrin deficiency: a clinical, genetic and transcriptional analysis. ( 22710133 )
2012
8
[Utilization of high-resolution melting analysis to screen patients with neonatal intrahepatic cholestasis caused by citrin deficiency]. ( 22487826 )
2012
9
Treatment with lactose (galactose)-restricted and medium-chain triglyceride-supplemented formula for neonatal intrahepatic cholestasis caused by citrin deficiency. ( 23430852 )
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 associated with citrin deficiency (NICCD): a case series of 11 Malaysian patients. ( 21161389 )
2010
12
Neonatal intrahepatic cholestasis caused by citrin deficiency in two Malaysian siblings: outcome at one year of life. ( 20200759 )
2010
13
Neonatal intrahepatic cholestasis caused by citrin deficiency (NICCD) in three Malay children. ( 20614727 )
2010
14
Liver transplantation for an infant with neonatal intrahepatic cholestasis caused by citrin deficiency using heterozygote living donor. ( 19413723 )
2010
15
Histological findings in the livers of patients with neonatal intrahepatic cholestasis caused by citrin deficiency. ( 20070398 )
2010
16
[Studies on the clinical manifestation and SLC25A13 gene mutation of Chinese patients with neonatal intrahepatic cholestasis caused by citrin deficiency]. ( 20376801 )
2010
17
Neonatal intrahepatic cholestasis caused by citrin deficiency (NICCD) as a cause of liver disease in infants in the UK. ( 19517266 )
2009
18
Neonatal intrahepatic cholestasis caused by citrin deficiency: clinical and laboratory investigation of 13 subjects in mainland of China. ( 19185551 )
2009
19
[Identification and diagnosis of three novel mutations in SLC25A13 gene of neonatal intrahepatic cholestasis caused by citrin deficiency]. ( 19099775 )
2008
20
Chubby face and the biochemical parameters for the early diagnosis of neonatal intrahepatic cholestasis caused by citrin deficiency. ( 18664871 )
2008
21
Clinical pictures of 75 patients with neonatal intrahepatic cholestasis caused by citrin deficiency (NICCD). ( 17323144 )
2007
22
Neonatal intrahepatic cholestasis caused by citrin deficiency in Korean infants. ( 18162705 )
2007
23
[SLC25A13 gene mutation analysis in a pedigree of neonatal intrahepatic cholestasis caused by citrin deficiency]. ( 17880783 )
2007
24
[A difficult and complicated case study: neonatal intrahepatic cholestasis caused by citrin deficiency]. ( 16613706 )
2006
25
Time course of acylcarnitine elevation in neonatal intrahepatic cholestasis caused by citrin deficiency. ( 16736097 )
2006
26
Hepatic steatosis and neonatal intrahepatic cholestasis caused by citrin deficiency (NICCD) in Taiwanese infants. ( 16737877 )
2006
27
A possible mechanism of neonatal intrahepatic cholestasis caused by citrin deficiency. ( 15777702 )
2005
28
Clinical heterogeneity of neonatal intrahepatic cholestasis caused by citrin deficiency: case reports from 16 patients. ( 15542392 )
2004
29
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
30
Mitochondrial aspartate glutamate carrier (citrin) deficiency as the cause of adult-onset type II citrullinemia (CTLN2) and idiopathic neonatal hepatitis (NICCD). ( 12111366 )
2002
31
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:

71
# 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 19)
# Gene Variation Type Significance SNP ID Assembly Location
1 SLC25A13 NM_014251.2(SLC25A13): c.1078C> T (p.Arg360Ter) single nucleotide variant Pathogenic rs80338721 GRCh37 Chromosome 7, 95813688: 95813688
2 SLC25A13 NM_014251.2(SLC25A13): c.1592G> A (p.Gly531Asp) single nucleotide variant Pathogenic rs80338724 GRCh37 Chromosome 7, 95751309: 95751309
3 SLC25A13 NM_014251.2(SLC25A13): c.15G> A (p.Lys5=) single nucleotide variant Pathogenic rs80338715 GRCh37 Chromosome 7, 95951254: 95951254
4 SLC25A13 NM_014251.2(SLC25A13): c.1750_1751[insNM_138459.3: 2672_24;1750+72_1751-4dup] complex Pathogenic
5 SLC25A13 NM_014251.2(SLC25A13): c.1801G> A (p.Glu601Lys) single nucleotide variant Pathogenic rs80338727 GRCh37 Chromosome 7, 95751007: 95751007
6 SLC25A13 NM_014251.2(SLC25A13): c.1801G> T (p.Glu601Ter) single nucleotide variant Pathogenic rs80338727 GRCh37 Chromosome 7, 95751007: 95751007
7 SLC25A13 NM_014251.2(SLC25A13): c.1813C> T (p.Arg605Ter) single nucleotide variant Pathogenic rs80338729 GRCh37 Chromosome 7, 95750995: 95750995
8 SLC25A13 NM_014251.2(SLC25A13): c.550C> T (p.Arg184Ter) single nucleotide variant Pathogenic rs80338716 GRCh37 Chromosome 7, 95822414: 95822414
9 SLC25A13 NM_014251.2(SLC25A13): c.615+1G> C single nucleotide variant Pathogenic rs80338718 GRCh37 Chromosome 7, 95822348: 95822348
10 SLC25A13 NM_014251.2(SLC25A13): c.615+5G> A single nucleotide variant Pathogenic rs80338717 GRCh37 Chromosome 7, 95822344: 95822344
11 SLC25A13 NM_014251.2(SLC25A13): c.1177+1G> A single nucleotide variant Pathogenic rs80338722 GRCh37 Chromosome 7, 95813588: 95813588
12 SLC25A13 NM_014251.2(SLC25A13): c.1799dupA (p.Tyr600Terfs) duplication Pathogenic rs80338726 GRCh37 Chromosome 7, 95751009: 95751009
13 SLC25A13 NM_014251.2(SLC25A13): c.852_855delTATG (p.Met285Profs) deletion Pathogenic rs80338720 GRCh37 Chromosome 7, 95818684: 95818687
14 SLC25A13 NM_014251.2(SLC25A13): c.1505C> T (p.Pro502Leu) single nucleotide variant Likely pathogenic rs139149160 GRCh38 Chromosome 7, 96131829: 96131829
15 SLC25A13 NM_014251.2(SLC25A13): c.775C> T (p.Gln259Ter) single nucleotide variant Pathogenic rs746155190 GRCh38 Chromosome 7, 96189654: 96189654
16 SLC25A13 NM_014251.2(SLC25A13): c.495delA (p.Ala166Profs) deletion Pathogenic rs879255504 GRCh38 Chromosome 7, 96193157: 96193157
17 SLC25A13 NM_014251.2(SLC25A13): c.955C> T (p.Arg319Ter) single nucleotide variant Pathogenic rs763191789 GRCh37 Chromosome 7, 95814302: 95814302
18 SLC25A13 NM_014251.2(SLC25A13): c.468+1G> C single nucleotide variant Likely pathogenic rs1060499612 GRCh37 Chromosome 7, 95838149: 95838149
19 SLC25A13 NM_014251.2(SLC25A13): c.1712delG (p.Arg571Leufs) deletion Pathogenic GRCh37 Chromosome 7, 95751189: 95751189

Expression for Citrullinemia, Type Ii, Neonatal-Onset

Search GEO for disease gene expression data for Citrullinemia, Type Ii, Neonatal-Onset.

Pathways for Citrullinemia, Type Ii, Neonatal-Onset

GO Terms for Citrullinemia, Type Ii, Neonatal-Onset

Sources for Citrullinemia, Type Ii, Neonatal-Onset

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
16 ExPASy
18 FMA
27 GO
28 GTR
29 HGMD
30 HMDB
31 HPO
32 ICD10
33 ICD10 via Orphanet
34 ICD9CM
35 IUPHAR
36 KEGG
37 LifeMap
39 MedGen
41 MeSH
42 MESH via Orphanet
43 MGI
45 NCI
46 NCIt
47 NDF-RT
50 NINDS
51 Novoseek
53 OMIM
54 OMIM via Orphanet
58 PubMed
60 QIAGEN
65 SNOMED-CT via HPO
66 SNOMED-CT via Orphanet
67 TGDB
68 Tocris
69 UMLS
70 UMLS via Orphanet
Content
Loading form....