NICCD
MCID: CTR077
MIFTS: 37

Citrullinemia, Type Ii, Neonatal-Onset (NICCD)

Categories: Genetic diseases, Liver diseases, Metabolic diseases, Rare 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 74 13 40 72
Neonatal Intrahepatic Cholestasis Caused by Citrin Deficiency 53 59 29 6
Niccd 57 53 59 74
Citrin Deficiency 53 74 72
Citrullinemia, Type Ii, Neonatal-Onset, with or Without Failure to Thrive and Dyslipidemia 57 74
Cholestasis, Neonatal Intrahepatic, Caused by Citrin Deficiency 57 74
Neonatal-Onset Citrullinemia Type Ii 53 74
Neonatal-Onset Citrullinemia Type 2 53 74
Cholestasis, Neonatal Intrahepatic, Caused by Citrin Deficiency; Niccd 57
Neonatal Intrahepatic Cholestasis Due to Citrin Deficiency 59
Adult-Onset Citrullinemia Type 2 72

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
MeSH 44 D002780
ICD10 via Orphanet 34 E72.2
UMLS via Orphanet 73 C1853942
Orphanet 59 ORPHA247598
MedGen 42 C1853942
UMLS 72 C1853942 C1863844 C1997910

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 citrullinemia, classic. An important gene associated with Citrullinemia, Type Ii, Neonatal-Onset is SLC25A13 (Solute Carrier Family 25 Member 13). The drugs carbamide peroxide and Liver Extracts have been mentioned in the context of this disorder. Affiliated tissues include liver and brain, and related phenotypes are failure to thrive and hypertriglyceridemia

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 : 74 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 top 50) (show all 57)
# Related Disease Score Top Affiliating Genes
1 citrullinemia, type ii, adult-onset 12.5
2 citrullinemia, classic 11.9
3 cholestasis 10.9
4 cholestasis, intrahepatic, of pregnancy, 1 10.7
5 carbonic anhydrase va deficiency, hyperammonemia due to 10.6
6 fatty liver disease 10.5
7 hypoglycemia 10.5
8 autosomal recessive disease 10.5
9 biliary atresia 10.5
10 lipid metabolism disorder 10.5
11 liver disease 10.4
12 galactosemia 10.4
13 bilirubin metabolic disorder 10.3
14 argininosuccinic aciduria 10.3
15 fatty liver disease, nonalcoholic 1 10.3
16 tyrosinemia 10.3
17 galactokinase deficiency 10.2
18 neonatal jaundice 10.2
19 subacute delirium 10.2
20 encephalopathy 10.2
21 hepatocellular carcinoma 10.1
22 ocular motor apraxia 10.1
23 phenylketonuria 10.1
24 abdominal obesity-metabolic syndrome 1 10.1
25 non-alcoholic fatty liver disease 10.1
26 syphilis 10.1
27 brain edema 10.1
28 hemolytic anemia 10.1
29 inherited metabolic disorder 10.1
30 urea cycle disorder 10.1
31 hyperphenylalaninemia 10.1
32 tremor 10.1
33 hypercholesterolemia, familial, 1 10.0
34 hypertriglyceridemia, familial 10.0
35 dowling-degos disease 1 10.0
36 tracheoesophageal fistula with or without esophageal atresia 10.0
37 glycogen storage disease ia 10.0
38 tyrosinemia, type i 10.0
39 anorexia nervosa 10.0
40 non-alcoholic steatohepatitis 10.0
41 esophageal atresia 10.0
42 familial hyperlipidemia 10.0
43 visual epilepsy 10.0
44 hepatic coma 10.0
45 hepatic encephalopathy 10.0
46 obstructive jaundice 10.0
47 glycogen storage disease 10.0
48 purpura 10.0
49 liver cirrhosis 10.0
50 rubella 10.0

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

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

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

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

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

Drugs for Citrullinemia, Type Ii, Neonatal-Onset (from DrugBank, HMDB, Dgidb, PharmGKB, IUPHAR, NovoSeek, BitterDB):


# Name Status Phase Clinical Trials Cas Number PubChem Id
1
carbamide peroxide Approved 124-43-6
2 Liver Extracts

Interventional clinical trials:


# Name Status NCT ID Phase Drugs
1 Prospective Cross-Sectional Non-invasive Assessment of Chronic Liver Disease in Urea Cycle Disorders Recruiting NCT03721367

Search 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, Brain

Publications for Citrullinemia, Type Ii, Neonatal-Onset

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

(show top 50) (show all 92)
# Title Authors PMID Year
1
Neonatal intrahepatic cholestasis caused by citrin deficiency: severe hepatic dysfunction in an infant requiring liver transplantation. 8 71
12424587 2002
2
Infantile cholestatic jaundice associated with adult-onset type II citrullinemia. 8 71
11343052 2001
3
Possible clinical and histologic manifestations of adult-onset type II citrullinemia in early infancy. 8 71
11343053 2001
4
Neonatal presentation of adult-onset type II citrullinemia. 8 71
11281457 2001
5
Identification of two novel mutations in the SLC25A13 gene and detection of seven mutations in 102 patients with adult-onset type II citrullinemia. 8 71
11153906 2000
6
The gene mutated in adult-onset type II citrullinaemia encodes a putative mitochondrial carrier protein. 8 71
10369257 1999
7
Genotypic and phenotypic features of citrin deficiency: five-year experience in a Chinese pediatric center. 38 8
21424115 2011
8
Citrin Deficiency 38 71
20301360 2005
9
Frequency and distribution in East Asia of 12 mutations identified in the SLC25A13 gene of Japanese patients with citrin deficiency. 38 8
16059747 2005
10
Screening of SLC25A13 mutations in early and late onset patients with citrin deficiency and in the Japanese population: Identification of two novel mutations and establishment of multiple DNA diagnosis methods for nine mutations. 38 8
11793471 2002
11
Mitochondrial aspartate glutamate carrier (citrin) deficiency as the cause of adult-onset type II citrullinemia (CTLN2) and idiopathic neonatal hepatitis (NICCD). 38 8
12111366 2002
12
A longitudinal study of urea cycle disorders. 8
25135652 2014
13
Type II citrullinaemia (citrin deficiency) in a neonate with hypergalactosaemia detected by mass screening. 8
11999983 2002
14
Current treatment for citrin deficiency during NICCD and adaptation/compensation stages: Strategy to prevent CTLN2. 38
31255436 2019
15
Growth impairment in individuals with citrin deficiency. 38
30715743 2019
16
Risk factors associated with mortality in neonatal intrahepatic cholestasis caused by citrin deficiency (NICCD) and clinical implications. 38
30642297 2019
17
Serum Amino Acid Profiling in Citrin-Deficient Children Exhibiting Normal Liver Function During the Apparently Healthy Period. 38
29654547 2019
18
Molecular and clinical characterization of citrin deficiency in a cohort of Chinese patients in Hong Kong. 38
30181955 2018
19
Medium-chain triglycerides supplement therapy with a low-carbohydrate formula can supply energy and enhance ammonia detoxification in the hepatocytes of patients with adult-onset type II citrullinemia. 38
29651749 2018
20
Cholesterol Metabolism Is Enhanced in the Liver and Brain of Children With Citrin Deficiency. 38
29659898 2018
21
[Analysis of SLC25A13 gene mutations in five infants with neonatal intrahepatic cholestasis caused by citrin deficiency]. 38
29419856 2018
22
Adult-onset type II citrullinemia: Current insights and therapy. 38
30588060 2018
23
Bile acid profiles in neonatal intrahepatic cholestasis caused by citrin deficiency. 38
28987776 2017
24
Analysis of islet beta cell functions and their correlations with liver dysfunction in patients with neonatal intrahepatic cholestasis caused by citrin deficiency (NICCD). 38
29137101 2017
25
Molecular diagnosis of citrin deficiency in an infant with intrahepatic cholestasis: identification of a 21.7kb gross deletion that completely silences the transcriptional and translational expression of the affected SLC25A13 allele. 38
29152073 2017
26
Blood glucose and insulin and correlation of SLC25A13 mutations with biochemical changes in NICCD patients. 38
28516797 2017
27
Biochemical and molecular characteristics of citrin deficiency in Korean children. 38
27829683 2017
28
p.Val452Ile mutation of the SLC25A13 gene in a Turkish patient with citrin deficiency. 38
29376577 2017
29
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. 38
27779681 2016
30
[Value of albumin in diagnosis of neonatal intrahepatic cholestasis caused by citrin deficiency]. 38
27938561 2016
31
Molecular diagnosis of pediatric patients with citrin deficiency in China: SLC25A13 mutation spectrum and the geographic distribution. 38
27405544 2016
32
Neonatal Intrahepatic Cholestasis Caused by Citrin Deficiency Differentiated from Biliary Atresia. 38
25988746 2016
33
Chronic hepatitis without hepatic steatosis caused by citrin deficiency in a child. 38
26190322 2016
34
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. 38
27127784 2016
35
[Treatment and Pathomechanism of Citrin Deficiency]. 38
26062589 2015
36
Detection of inborn errors of metabolism using GC-MS: over 3 years of experience in southern China. 38
25781538 2015
37
Novel mutations in the SLC25A13 gene in a patient with NICCD and severe manifestations. 38
25381944 2015
38
Inspissated bile syndrome in an infant with citrin deficiency and congenital anomalies of the biliary tract and esophagus: identification and pathogenicity analysis of a novel SLC25A13 mutation with incomplete penetrance. 38
25216257 2014
39
First Bulgarian case of citrin deficiency caused by one novel and one recurrent mutation in the SLC25A13 gene. 38
25365849 2014
40
Medium-chain triglyceride supplementation under a low-carbohydrate formula is a promising therapy for adult-onset type II citrullinemia. 38
27896073 2014
41
Clinical, molecular and functional investigation on an infant with neonatal intrahepatic cholestasis caused by citrin deficiency (NICCD). 38
24586645 2014
42
A novel mutation of the SLC25A13 gene in a Chinese patient with citrin deficiency detected by target next-generation sequencing. 38
24161253 2014
43
[Characteristics of the plasma amino acid spectrum of neonatal intrahepatic cholestasis caused by citrin deficiency]. 38
24636297 2013
44
Prediction of the functional effect of novel SLC25A13 variants using a S. cerevisiae model of AGC2 deficiency. 38
23053473 2013
45
SLC25A13 gene analysis in citrin deficiency: sixteen novel mutations in East Asian patients, and the mutation distribution in a large pediatric cohort in China. 38
24069319 2013
46
Effects of supplementation on food intake, body weight and hepatic metabolites in the citrin/mitochondrial glycerol-3-phosphate dehydrogenase double-knockout mouse model of human citrin deficiency. 38
22921887 2012
47
Neonatal intrahepatic cholestasis caused by citrin deficiency: prevalence and SLC25A13 mutations among Thai infants. 38
23067347 2012
48
Biochemical characteristics of neonatal cholestasis induced by citrin deficiency. 38
23112554 2012
49
Cloning and sequence analysis of SLC25A13 transcripts in human amniocytes. 38
26835269 2012
50
Diagnosis of neonatal intrahepatic cholestasis caused by citrin deficiency using high-resolution melting analysis and a clinical scoring system. 38
22575253 2012

Variations for Citrullinemia, Type Ii, Neonatal-Onset

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

6 (show all 25)
# Gene Variation Type Significance SNP ID GRCh37 Pos GRCh38 Pos
1 SLC25A13 NM_014251.3(SLC25A13): c.1177+1G> A single nucleotide variant Pathogenic rs80338722 7:95813588-95813588 7:96184276-96184276
2 SLC25A13 NM_014251.3(SLC25A13): c.1799dup (p.Tyr600Ter) duplication Pathogenic rs80338726 7:95751009-95751009 7:96121697-96121697
3 SLC25A13 NM_014251.3(SLC25A13): c.1078C> T (p.Arg360Ter) single nucleotide variant Pathogenic rs80338721 7:95813688-95813688 7:96184376-96184376
4 SLC25A13 NM_014251.3(SLC25A13): c.1592G> A (p.Gly531Asp) single nucleotide variant Pathogenic rs80338724 7:95751309-95751309 7:96121997-96121997
5 SLC25A13 NM_014251.3(SLC25A13): c.15G> A (p.Lys5=) single nucleotide variant Pathogenic rs80338715 7:95951254-95951254 7:96321942-96321942
6 SLC25A13 NM_014251.2(SLC25A13): c.1750_1751[insNM_138459.3: 2672_24;1750+72_1751-4dup] complex Pathogenic
7 SLC25A13 NM_014251.3(SLC25A13): c.1801G> A (p.Glu601Lys) single nucleotide variant Pathogenic rs80338727 7:95751007-95751007 7:96121695-96121695
8 SLC25A13 NM_014251.3(SLC25A13): c.1801G> T (p.Glu601Ter) single nucleotide variant Pathogenic rs80338727 7:95751007-95751007 7:96121695-96121695
9 SLC25A13 NM_014251.3(SLC25A13): c.1813C> T (p.Arg605Ter) single nucleotide variant Pathogenic rs80338729 7:95750995-95750995 7:96121683-96121683
10 SLC25A13 NM_014251.3(SLC25A13): c.550C> T (p.Arg184Ter) single nucleotide variant Pathogenic rs80338716 7:95822414-95822414 7:96193102-96193102
11 SLC25A13 NM_014251.3(SLC25A13): c.615+1G> C single nucleotide variant Pathogenic rs80338718 7:95822348-95822348 7:96193036-96193036
12 SLC25A13 NM_014251.3(SLC25A13): c.852_855del (p.Met285fs) deletion Pathogenic rs80338720 7:95818684-95818687 7:96189372-96189375
13 SLC25A13 NM_014251.3(SLC25A13): c.775C> T (p.Gln259Ter) single nucleotide variant Pathogenic rs746155190 7:95818966-95818966 7:96189654-96189654
14 SLC25A13 NM_014251.3(SLC25A13): c.495del (p.Ala166fs) deletion Pathogenic rs879255504 7:95822469-95822469 7:96193157-96193157
15 SLC25A13 NM_014251.3(SLC25A13): c.1664_1665insAGATTACAGGTGGCTGCCCGGGG (p.Gln556fs) insertion Pathogenic 7:95751236-95751237 7:96121924-96121925
16 SLC25A13 NM_014251.3(SLC25A13): c.493C> T (p.Gln165Ter) single nucleotide variant Pathogenic 7:95822471-95822471 7:96193159-96193159
17 SLC25A13 NM_014251.3(SLC25A13): c.615+5G> A single nucleotide variant Pathogenic/Likely pathogenic rs80338717 7:95822344-95822344 7:96193032-96193032
18 SLC25A13 NM_014251.3(SLC25A13): c.468+1G> C single nucleotide variant Likely pathogenic rs1060499612 7:95838149-95838149 7:96208837-96208837
19 SLC25A13 NM_014251.3(SLC25A13): c.1064G> A (p.Arg355Gln) single nucleotide variant Uncertain significance rs398122839 7:95813702-95813702 7:96184390-96184390
20 SLC25A13 NM_014251.3(SLC25A13): c.1910T> C (p.Val637Ala) single nucleotide variant Uncertain significance rs148962110 7:95750621-95750621 7:96121309-96121309
21 SLC25A13 NM_014251.3(SLC25A13): c.1267G> A (p.Asp423Asn) single nucleotide variant Uncertain significance 7:95799401-95799401 7:96170089-96170089
22 SLC25A13 NM_014251.3(SLC25A13): c.616-11A> G single nucleotide variant Uncertain significance rs879255503 7:95820570-95820570 7:96191258-96191258
23 SLC25A13 NM_014251.3(SLC25A13): c.1958A> G (p.Lys653Arg) single nucleotide variant Uncertain significance rs879255501 7:95750573-95750573 7:96121261-96121261
24 SLC25A13 NM_014251.3(SLC25A13): c.1505C> T (p.Pro502Leu) single nucleotide variant Uncertain significance rs139149160 7:95761141-95761141 7:96131829-96131829
25 SLC25A13 NM_014251.3(SLC25A13): c.1311C> T (p.Cys437=) single nucleotide variant Uncertain significance rs879255502 7:95799357-95799357 7:96170045-96170045

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

74
# Symbol AA change Variation ID SNP ID
1 SLC25A13 p.Glu601Lys VAR_016601 rs80338727

Expression for Citrullinemia, Type Ii, Neonatal-Onset

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

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GO Terms for Citrullinemia, Type Ii, Neonatal-Onset

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