Neonatal-onset citrullinemia type 2

An autosomal recessive metabolic disorder characterized by poor growth, INTRAHEPATIC CHOLESTASIS, and citrullinemia. Most patients show spontaneous improvement by 1 year of age; others may have a progressive course with continued failure to thrive and DYSLIPIDEMIA caused by citrin deficiency, and some may develop chronic or fatal LIVER DISEASE. Mutations in the SLC25A13 gene have been identified. OMIM: 605814

Also Known As:

Networked: 88 relevant articles (4 outcomes, 7 trials/studies)

Relationship Network

Disease Context: Research Results

Related Diseases

1.	Cholestasis
2.	Liver Failure
3.	Neonatal-onset citrullinemia type 2
4.	Citrullinemia
5.	Intrahepatic Cholestasis

Experts

1.	Kobayashi, Keiko: 28 articles (01/2013 - 01/2002)
2.	Saheki, Takeyori: 24 articles (04/2016 - 01/2002)
3.	Song, Yuan-Zong: 11 articles (10/2017 - 04/2006)
4.	Ushikai, Miharu: 8 articles (11/2012 - 01/2005)
5.	Iijima, Mikio: 7 articles (01/2008 - 02/2002)
6.	Ohura, Toshihiro: 6 articles (01/2019 - 05/2003)
7.	Zhang, Zhan-Hui: 6 articles (10/2017 - 03/2012)
8.	Numakura, Chikahiko: 5 articles (01/2022 - 01/2014)
9.	Hayasaka, Kiyoshi: 5 articles (01/2021 - 01/2014)
10.	Okano, Yoshiyuki: 5 articles (01/2019 - 11/2002)

Drugs and Biologics

Drugs and Important Biological Agents (IBA) related to Neonatal-onset citrullinemia type 2:

1.	Triglycerides (Triacylglycerol)IBA 01/01/2021 - "Medium-chain triglyceride (MCT) supplementation with a lactose-restricted formula and MCT supplementation under a low-carbohydrate diet are recommended for NICCD and CTLN2, respectively. " 01/01/2018 - "Patients with NICCD present with intrahepatic cholestasis in the neonatal period and usually respond to the treatment with medium-chain triglyceride (MCT) supplement and lactose-restricted formula. " 06/01/2015 - "We noticed that a lactose (galactose)-restricted and medium-chain triglyceride (MCT)-supplemented formula is notably effective for patients with NICCD. " 01/01/2014 - "We previously reported that a lactose (galactose)-restricted and medium-chain triglyceride (MCT)-supplemented formula is notably effective for patients with NICCD. " 09/01/2012 - "The diagnoses were NICCD and multiple ovarian antral follicles (minipuberty), and the patient responded well to a galactose-free and medium chain triglyceride (MCT)-enriched formula. "
2.	Galactose (Galactopyranose)FDA LinkGeneric 01/01/2012 - "Early treatment with lactose (galactose)-restricted and MCT-supplemented formula is recommended for patients with NICCD and possibly for patients with CTLN2." 10/01/2004 - "To clarify the perinatal and neonatal effects and the inconsistent results on NMS, we examined aminograms, the levels of bile acids and galactose in dried blood spots for NMS from 20 patients with NICCD. " 05/01/2003 - "A novel inborn error of metabolism detected by elevated methionine and/or galactose in newborn screening: neonatal intrahepatic cholestasis caused by citrin deficiency." 06/01/2015 - "We noticed that a lactose (galactose)-restricted and medium-chain triglyceride (MCT)-supplemented formula is notably effective for patients with NICCD. " 01/01/2014 - "We previously reported that a lactose (galactose)-restricted and medium-chain triglyceride (MCT)-supplemented formula is notably effective for patients with NICCD. "
3.	LactoseFDA LinkGeneric 01/01/2012 - "Early treatment with lactose (galactose)-restricted and MCT-supplemented formula is recommended for patients with NICCD and possibly for patients with CTLN2." 01/01/2021 - "Medium-chain triglyceride (MCT) supplementation with a lactose-restricted formula and MCT supplementation under a low-carbohydrate diet are recommended for NICCD and CTLN2, respectively. " 01/01/2018 - "Patients with NICCD present with intrahepatic cholestasis in the neonatal period and usually respond to the treatment with medium-chain triglyceride (MCT) supplement and lactose-restricted formula. " 06/01/2015 - "We noticed that a lactose (galactose)-restricted and medium-chain triglyceride (MCT)-supplemented formula is notably effective for patients with NICCD. " 01/01/2014 - "We previously reported that a lactose (galactose)-restricted and medium-chain triglyceride (MCT)-supplemented formula is notably effective for patients with NICCD. "
4.	AntralIBA 09/01/2012 - "Multiple ovarian antral follicles in a preterm infant with neonatal intrahepatic cholestasis caused by citrin deficiency: a clinical, genetic and transcriptional analysis." 09/01/2012 - "The diagnoses were NICCD and multiple ovarian antral follicles (minipuberty), and the patient responded well to a galactose-free and medium chain triglyceride (MCT)-enriched formula. "
5.	Messenger RNA (mRNA)IBA 10/01/2012 - "This study will provide laboratory evidences for prenatal diagnosis of NICCD at mRNA level. " 10/01/2012 - "Normal mRNA occupied majority of the transcripts in normal control and heterozygous amniocytes which contained normal allele and 851del4 mutation, indicating that the two fetuses wouldn't suffer from NICCD. " 03/01/2012 - "Normal mRNA predominated in the transcripts in normal control and 851del4 mutation carrier, suggesting that the two fetuses were not at risk for NICCD. " 03/01/2012 - "This study will provide laboratory evidence for prenatal diagnosis of neonatal intrahepatic cholestasis caused by citrin deficiency (NICCD) at mRNA level. "
6.	Bile Acids and Salts (Bile Acids)IBA 12/01/2017 - "The area under receiver operating characteristic curve for conjugated/free bile acid ratio to identify infants with NICCD was 0.871 (95% confidence interval, 0.713-1.0). " 12/01/2017 - "The calculated ratios, including primary/secondary bile acid (714 vs. 235, p<0.05) and conjugated/free bile acid (371 vs. 125, p<0.05) ratios, were higher in NICCD infants. " 12/01/2017 - "We established a liquid chromatography tandem mass spectrometry (LC-MS/MS) method for simultaneously quantifying plasma bile acids and examined bile acid profiles in NICCD infants. " 12/01/2017 - "Bile acid profiles in neonatal intrahepatic cholestasis caused by citrin deficiency." 10/21/2012 - "Compared with BA and INC patients, the NICCD patients had significantly higher levels of total bile acid (TBA) [all measures are expressed as median (inter-quartile range): 178.0 (111.2-236.4) μmol/L in NICCD vs 112.0 (84.9-153.9) μmol/L in BA and 103.0 (70.9-135.3) μmol/L in INC, P = 0.0001]. "
7.	DNA (Deoxyribonucleic Acid)IBA 04/01/2011 - "This study aimed to identify the mutation type of NICCD patients by DNA sequencing. " 03/01/2018 - "We investigated 12 neonates with NICCD who were initially considered normal in newborn mass screening (NBS) by tandem mass spectrometry, but were later diagnosed with NICCD by DNA tests. " 06/01/2008 - "Genomic DNA was extracted from blood samples of 3 NICCD patients from Taiwan (P757), Guangdong (P1194) and Hebei province (P1443) of China, respectively, and all the 18 exons and their flanking sequences of SLC25A13 gene were sequenced. " 02/01/2002 - "Multiple DNA diagnoses for the nine mutations revealed that 100 (male/female: 70/30) out of 115 CTLN2 and 38 (14/24) out of 45 NICCD patients tested were homozygotes or compound heterozygotes. " 01/01/2013 - "By means of direct DNA sequencing, cDNA cloning and SNP analyses, 16 novel pathogenic mutations, including 9 missense, 4 nonsense, 1 splice-site, 1 deletion and 1 large transposal insertion IVS4ins6kb (GenBank accession number KF425758), were identified in CTLN2 or NICCD patients from China, Japan and Malaysia, respectively, making the SLC25A13 variations worldwide reach the total number of 81. "
8.	Complementary DNA (cDNA)IBA 12/01/2016 - "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." 12/01/2016 - "The present study confirmed the effectiveness of this formula in NICCD therapy, enriched the SLC25A13 mutational spectrum and supported the feasibility of cDNA cloning analysis using PBLs as a molecular tool for facilitating the identification of large SLC25A13 deletions." 01/01/2013 - "By means of direct DNA sequencing, cDNA cloning and SNP analyses, 16 novel pathogenic mutations, including 9 missense, 4 nonsense, 1 splice-site, 1 deletion and 1 large transposal insertion IVS4ins6kb (GenBank accession number KF425758), were identified in CTLN2 or NICCD patients from China, Japan and Malaysia, respectively, making the SLC25A13 variations worldwide reach the total number of 81. "
9.	Insulin (Novolin)FDA Link 11/01/2017 - "A linear correlation was found between FBG and fasting insulin (P < .001) and between FBG and C-P in the NICCD patients (P = .001). " 01/01/2017 - "Blood glucose and insulin and correlation of SLC25A13 mutations with biochemical changes in NICCD patients." 01/01/2017 - "This study aimed to explore the characteristics of fasting blood glucose (FBG), fasting insulin (FINS) and C-peptide (C-P) levels in NICCD infants, analyze their SLC25A13 genetic mutations and further discuss the correlation between SLC25A13 genetic mutations and biochemical changes. " 11/01/2017 - "The differences in fasting blood glucose (FBG), fasting insulin, C-peptide (C-P), the homeostasis model of assessment for the insulin resistance index (HOMA-IR), fasting beta cell function (FBCI), and the HOMA beta cell function index (HBCI) between the NICCD and control groups were not significant (P > .05). "
10.	C-PeptideIBA 01/01/2017 - "This study aimed to explore the characteristics of fasting blood glucose (FBG), fasting insulin (FINS) and C-peptide (C-P) levels in NICCD infants, analyze their SLC25A13 genetic mutations and further discuss the correlation between SLC25A13 genetic mutations and biochemical changes. " 11/01/2017 - "The differences in fasting blood glucose (FBG), fasting insulin, C-peptide (C-P), the homeostasis model of assessment for the insulin resistance index (HOMA-IR), fasting beta cell function (FBCI), and the HOMA beta cell function index (HBCI) between the NICCD and control groups were not significant (P > .05). "

Therapies and Procedures

1.	Liver Transplantation 01/01/2022 - "Liver transplantation has been performed in only 4 patients (1 NICCD, 3 CTLN2) with a good response thereafter. " 01/01/2019 - "There has been reports of mortalities or liver transplants associated with NICCD, but risk factors associated with poor outcome were unknown. " 01/01/2012 - "Most patients with NICCD show a resolution of symptoms within the first year of life, but some patients present with severe symptoms and require liver transplantation. " 11/01/2010 - "Liver transplantation for an infant with neonatal intrahepatic cholestasis caused by citrin deficiency using heterozygote living donor." 11/01/2002 - "we report the first case of neonatal intrahepatic cholestasis caused by citrin deficiency with severe hepatic dysfunction requiring a living-related liver transplantation. "
2.	Therapeutics 12/01/2016 - "The present study confirmed the effectiveness of this formula in NICCD therapy, enriched the SLC25A13 mutational spectrum and supported the feasibility of cDNA cloning analysis using PBLs as a molecular tool for facilitating the identification of large SLC25A13 deletions."
3.	Carbohydrate-Restricted Diet (Low Carbohydrate Diet) 01/01/2021 - "Medium-chain triglyceride (MCT) supplementation with a lactose-restricted formula and MCT supplementation under a low-carbohydrate diet are recommended for NICCD and CTLN2, respectively. "
4.	Transplantation 11/01/2010 - "Diagnosis of NICCD was established before transplantation, and donor evaluation included mutation in the SLC25A13 gene for exclusion of individuals with citrin deficiency citrullinemia. "
5.	Total Parenteral Nutrition 08/01/2009 - "Among the 39 cases with identified etiologies, inherited metabolic diseases were on top of the list, including 6 kinds and 27 cases in total, i.e., neonatal intrahepatic cholestasis caused by citrin deficiency (NICCD, 21 cases), transient galactosemia, tyrosinemia type I, galactose kinase deficiency, ornithine carbamoyl transferase deficiency and glycogen storage disease type I, followed by acquired causes (7 cases in total), such as total parenteral nutrition associated cholestasis (TPNAC), congenital syphilis and CMV hepatitis; and then biliary tract malformation (5 cases in total), including biliary atresia, Caroli's disease and gallbladder polyp, were the third. "