Adult-onset citrullinemia type 2

An autosomal recessive metabolic disorder characterized by the sudden onset of various neuropsychologic symptoms, convulsions, and coma due to HYPERAMMONEMIA. In some cases, rapid progression can lead to BRAIN EDEMA and death if liver transplantation is not possible. Some patients may present with nonalcoholic LIVER STEATOSIS; LIVER CIRRHOSIS; or HEPATOCELLULAR CARCINOMA. Patients also tend to have an aversion to carbohydrates, and favor proteins in their diet. Mutations in the SLC25A13 gene have been identified. OMIM: 603471

Also Known As:

Networked: 104 relevant articles (6 outcomes, 3 trials/studies)

Relationship Network

Disease Context: Research Results

Related Diseases

1.	Disease Progression
2.	Hyperammonemia
3.	Galactosemias (Galactosemia)
4.	Vomiting
5.	Citrullinemia

Experts

1.	Saheki, Takeyori: 27 articles (01/2020 - 01/2002)
2.	Kobayashi, Keiko: 24 articles (01/2017 - 01/2002)
3.	Song, Yuan-Zong: 10 articles (01/2019 - 11/2008)
4.	Yazaki, Masahide: 8 articles (09/2021 - 03/2005)
5.	Numakura, Chikahiko: 7 articles (01/2022 - 01/2014)
6.	Ohura, Toshihiro: 7 articles (09/2021 - 05/2003)
7.	Hayasaka, Kiyoshi: 7 articles (01/2021 - 01/2014)
8.	Moriyama, Mitsuaki: 7 articles (01/2020 - 04/2004)
9.	Sinasac, David S: 7 articles (12/2019 - 05/2006)
10.	Okano, Yoshiyuki: 6 articles (09/2021 - 01/2007)

Drugs and Biologics

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

1.	Amino AcidsFDA Link 09/08/2023 - "Improved sensitivity and specificity for citrin deficiency using selected amino acids and acylcarnitines in the newborn screening." 10/02/2019 - "[Newborn screening program and blood amino acid profiling in early neonates with citrin deficiency]." 02/01/2017 - "We concluded that Korean patients with citrin deficiency showed the highest frequency of the IVS16ins3kb mutation and that plasma amino-acid profiles can be used to differentiate between NICCD and INH." 12/01/2016 - "We checked blood amino acids and acylcarnitines in 38 patients, which revealed phenylketonuria (PKU) in 2 patients, and one with suspected citrin deficiency. " 03/01/2008 - "High citrulline (293 micromol/L), on initial plasma amino acid, suggested the diagnosis of citrin deficiency. "
2.	Glucose (Dextrose)FDA LinkGeneric 06/01/2020 - "Hyperalimentation was also reported to exacerbate CTLN2; however, glucose toxicity was unclear in citrin deficiency. " 06/01/2020 - "Diabetes mellitus exacerbates citrin deficiency via glucose toxicity." 06/01/2020 - "Insulin therapy with MCT supplementation and a low-carbohydrate diet improved hyperammonemia and liver function in Case 1. Additional insulin therapy improved hyperammonemia in Case 2. Glucose is not toxic for citrin deficiency in normoglycemia because glucose uptake and metabolism by hepatocytes are limited in normoglycemia. " 01/01/2021 - "Hepatocytes with citrin deficiency cannot use glucose and fatty acids as energy sources due to defects in the NADH shuttle and downregulation of peroxisome proliferator-activated receptor α (PPARα), respectively. "
3.	Messenger RNA (mRNA)IBA 01/01/2019 - "We demonstrate the efficacy of hCitrin-mRNA-LNP therapy in cultured human cells and in a murine model of citrin deficiency that resembles the human condition. " 01/01/2019 - "mRNA Therapy Improves Metabolic and Behavioral Abnormalities in a Murine Model of Citrin Deficiency." 01/01/2019 - "In conclusion, mRNA-LNP therapy could have a significant therapeutic effect on the treatment of citrin deficiency and other mitochondrial enzymopathies with limited treatment options." 01/01/2019 - "To develop a new class of therapy for citrin deficiency, codon-optimized mRNA encoding human citrin (hCitrin) was encapsulated in lipid nanoparticles (LNPs). "
4.	Insulin (Novolin)FDA Link 06/01/2020 - "Insulin therapy with MCT supplementation and a low-carbohydrate diet improved hyperammonemia and liver function in Case 1. Additional insulin therapy improved hyperammonemia in Case 2. Glucose is not toxic for citrin deficiency in normoglycemia because glucose uptake and metabolism by hepatocytes are limited in normoglycemia. "
5.	CreatinineIBA 03/01/2022 - "Therefore, the serum BUN or BUN/creatinine ratio may help to identify patients with citrin deficiency during newborn screening. " 03/01/2022 - "Usefulness of serum BUN or BUN/creatinine ratio as markers for citrin deficiency in positive cases of newborn screening."
6.	Desflurane (I 653)FDA Link 03/04/2022 - "General anesthesia of the shortest duration with the least metabolized drugs using desflurane and remifentanil, would be beneficial for rapid emergence in surgical patients with citrin deficiency. " 03/04/2022 - "Desflurane and remifentanil anesthesia in a child with citrin deficiency: A case report."
7.	Remifentanil (Ultiva)FDA Link 03/04/2022 - "General anesthesia of the shortest duration with the least metabolized drugs using desflurane and remifentanil, would be beneficial for rapid emergence in surgical patients with citrin deficiency. " 03/04/2022 - "Desflurane and remifentanil anesthesia in a child with citrin deficiency: A case report."
8.	citrinIBA 09/08/2023 - "Citrin deficiency is an autosomal recessive disorder caused by a defect of citrin resulting from mutations in the SLC25A13 gene. " 05/01/2021 - "In western blots of liver biopsy samples, normal citrin levels were observed, suggesting that adult-onset citrullinemia type 2 (CTLN2) was not present. " 01/01/2019 - "Characteristic growth impairment in citrin deficiency suggests a significant role of citrin in the catch-up growth via lipogenesis." 01/01/2019 - "A genetic analysis of solute carrier family 25, member 13 revealed the presence of a homozygous 851del4 mutation, and a diagnosis of citrin deficiency was made. " 01/01/2009 - "The finding of citrin mutations in patients of Arabic, Pakistani, French Canadian and Northern European origins supports the concept that citrin deficiency is a panethnic disease."
9.	Galactose (Galactopyranose)FDA LinkGeneric 03/01/2008 - "Four weeks later, this patient was switched to a galactose-free formula (as recommended in citrin deficiency with galactosemia) and her pathological status returned to normal. " 03/01/2008 - "Citrin deficiency was later ruled out by molecular biology studies; then we reintroduced a galactose-containing formula which re-evoked rapidly vomiting, galactose aversion and hepatic cytolysis and the diagnosis of classical galactosemia was established. " 12/01/2020 - "This method helps in diagnosis and follow-up of several inherited metabolic diseases connected to galactose metabolism deficiency such as galactosemia, glycogenosis, glycosylation, tyrosinemia and citrin deficiency. " 01/30/2011 - "Development of a galactose biosensor with galactose oxidase-immobilized epidermis of Solanum lycopersicum: potential point-of-care testing for citrin deficiency in high-prevalence areas." 03/01/2022 - "Citrin deficiency belongs to a group of urea cycle disorders that can be identified during newborn screening by measuring citrulline, phenylalanine, methionine, and galactose levels. "
10.	Sucrose (Saccharose)IBA 08/24/2007 - "The resulting double knock-out mice demonstrated citrullinemia, hyperammonemia that was further elevated by oral sucrose administration, hypoglycemia, and a fatty liver, all features of human citrin deficiency. " 01/01/2017 - "In this study, we investigated the voluntary oral intake and preference for sucrose, glycerol or ethanol solutions by wild-type, citrin (Ctrn)-knockout (KO), mGPD-KO, and Ctrn/mGPD double-KO mice; all substances that are known or suspected precipitating factors in the pathogenesis of human citrin deficiency. " 12/01/2011 - "Overall, we have identified additional metabolic disturbances in double-KO mice following oral sucrose administration, and provided further evidence for the therapeutic use of sodium pyruvate in our mouse model of citrin deficiency."

Therapies and Procedures

1.	Therapeutics 01/01/2022 - "As a nationwide study to investigate the clinical manifestations, medical therapy, and long-term outcome in Japanese patients with citrin deficiency, we collected clinical data of 222 patients diagnosed and/or treated at various different institutions between January 2000 and December 2019. " 06/01/2015 - "MCT supplementation could be a promising therapy for citrin deficiency. " 09/01/2013 - "Citrin deficiency in a Romanian child living in Spain highlights the worldwide distribution of this defect and illustrates the value of nutritional therapy." 01/01/2019 - "We demonstrate the efficacy of hCitrin-mRNA-LNP therapy in cultured human cells and in a murine model of citrin deficiency that resembles the human condition. " 06/01/2023 - "This large difference in endogenous aralar levels partly explains the high residual MAS activity in liver of citrin(-/-) mice and why they fail to recapitulate the human disease, but supports the benefit of increasing aralar expression to improve the redox balance capacity of human liver, as an effective therapy for CITRIN deficiency."
2.	Carbohydrate-Restricted Diet (Low Carbohydrate Diet) 06/01/2020 - "Hepatic glycolysis is essentially impaired in citrin deficiency and a low-carbohydrate diet was recommended. " 01/01/2022 - "This study reports the diagnosis and clinical course in a large cohort of patients with citrin deficiency and suggests that early intervention including a low carbohydrate diet and MCT supplementation can be associated with improved clinical course and long-term outcome." 01/01/2019 - "He preferred a high-protein, high-fat, low-carbohydrate diet, which has been observed in many patients with citrin deficiency, but no clinical features of adult-onset type II citrullinemia were observed. " 06/01/2020 - "Insulin therapy with MCT supplementation and a low-carbohydrate diet improved hyperammonemia and liver function in Case 1. Additional insulin therapy improved hyperammonemia in Case 2. Glucose is not toxic for citrin deficiency in normoglycemia because glucose uptake and metabolism by hepatocytes are limited in normoglycemia. "
3.	General Anesthesia 03/04/2022 - "A 5-year-old girl with citrin deficiency was scheduled for blepharoplasty under general anesthesia. " 03/04/2022 - "Hyperammonemia, metabolic derangement, and/or the prolonged effects of anesthetics may lead to delayed emergence from general anesthesia as well as the onset of type 2 citrullinemia, even in compensated patients with citrin deficiency. " 03/04/2022 - "General anesthesia of the shortest duration with the least metabolized drugs using desflurane and remifentanil, would be beneficial for rapid emergence in surgical patients with citrin deficiency. "
4.	Liver Transplantation 01/01/2023 - "A hybrid procedure of living donor liver transplantation for a pediatric patient with citrin deficiency." 01/01/2019 - "Although dietary approaches have shown some benefits in managing citrin deficiency, the only curative treatment option for these patients is liver transplantation, which is high-risk and associated with long-term complications because of chronic immunosuppression. " 06/21/2015 - "This case demonstrates that citrin deficiency can present in late infancy as acute liver failure triggered by infection, and may require liver transplantation. " 10/04/2023 - "Except for those with Citrin deficiency or liver transplantation, all pediatric patients require lifelong low protein diet with safe levels of protein intake and adequate energy and lipids supply for their corresponding age; if necessary supplementing essential amino acids and protein-free milk are also needed. " 12/01/2008 - "It is suggested that the administration of arginine and sodium pyruvate with low-carbohydrate meals may be an effective therapy in patients with citrin deficiency in order either to prolong metabolic normalcy or to provide a safer and more affordable alternative to liver transplantation."
5.	Protein-Restricted Diet (Diet, Protein Restricted) 01/01/2010 - "Owing to the high carbohydrate content, the conventional low-protein diet therapy should be avoided in patients with hepatic encephalopathy associated with citrin deficiency. " 10/04/2023 - "Except for those with Citrin deficiency or liver transplantation, all pediatric patients require lifelong low protein diet with safe levels of protein intake and adequate energy and lipids supply for their corresponding age; if necessary supplementing essential amino acids and protein-free milk are also needed. "