Inborn Urea Cycle Disorders

Rare congenital metabolism disorders of the urea cycle. The disorders are due to mutations that result in complete (neonatal onset) or partial (childhood or adult onset) inactivity of an enzyme, involved in the urea cycle. Neonatal onset results in clinical features that include irritability, vomiting, lethargy, seizures, NEONATAL HYPOTONIA; RESPIRATORY ALKALOSIS; HYPERAMMONEMIA; coma, and death. Survivors of the neonatal onset and childhood/adult onset disorders share common risks for ENCEPHALOPATHIES, METABOLIC, INBORN; and RESPIRATORY ALKALOSIS due to HYPERAMMONEMIA.

Also Known As:

Networked: 569 relevant articles (16 outcomes, 36 trials/studies)

Relationship Network

Disease Context: Research Results

Related Diseases

1.	Ornithine Carbamoyltransferase Deficiency Disease
2.	Methylmalonic acidemia
3.	Argininosuccinic Aciduria
4.	Hyperammonemia
5.	Hyperargininemia

Experts

1.	Häberle, Johannes: 32 articles (12/2021 - 10/2002)
2.	Lee, Brendan: 21 articles (09/2016 - 12/2002)
3.	Diaz, George A: 17 articles (07/2022 - 08/2008)
4.	Lichter-Konecki, Uta: 13 articles (01/2021 - 08/2008)
5.	Nagamani, Sandesh C S: 11 articles (03/2021 - 05/2012)
6.	Berry, Susan A: 11 articles (01/2021 - 05/2007)
7.	McCandless, Shawn E: 11 articles (01/2021 - 06/2013)
8.	Pahan, Kalipada: 10 articles (12/2021 - 04/2003)
9.	Longo, Nicola: 10 articles (12/2021 - 06/2013)
10.	Burgard, Peter: 10 articles (11/2019 - 06/2011)

Drugs and Biologics

Drugs and Important Biological Agents (IBA) related to Inborn Urea Cycle Disorders:

1.	AmmoniaIBA 07/01/2015 - "The aim of this study was to examine predictors of ammonia exposure and hyperammonemic crises in patients with urea cycle disorders. " 11/07/2023 - "Urea cycle disorders (UCDs) cause elevations in ammonia which, when severe, cause irreversible neurologic injury. " 01/01/2023 - "While disruption of the functions of CPS1 leads to elevated ammonia and nerve damage in the body, mainly manifested as urea cycle disorder. " 01/01/2021 - "Urea cycle disorders (UCDs), inborn errors of hepatocyte metabolism, result in the systemic accumulation of ammonia to toxic levels. " 03/01/2020 - "ECMO as a Platform for Rapid Ammonia Removal in a Neonate with Multienzyme Urea Cycle Disorder."
2.	N-carbamylglutamateIBA 12/01/2021 - "NAGSD is the only urea cycle disorder that can be effectively treated with a single drug, N-carbamylglutamate (NCG), a stable NAG analog, which activates CPS1 to restore ureagenesis. " 10/18/2018 - "NAGSD is the only urea cycle disorder that can be treated with a single drug, N-carbamylglutamate (NCG), which can activate CPS1 and completely restore ureagenesis in patients with NAGSD. " 09/01/2016 - "Although NAGS deficiency is the rarest urea cycle disorder, it is the only one that can be specifically and effectively treated by a drug, N-carbamylglutamate, a stable structural analogous of NAG that activates CPS1. " 10/17/2023 - "NAGS deficiency (NAGSD) is the rarest of the urea cycle disorders, yet is unique in that ureagenesis can be restored with the drug N-carbamylglutamate (NCG). " 05/01/2013 - "N-carbamylglutamate is approved for the treatment of hyperammonemia in N-acetylglutamate synthetase deficiency and may have efficacy in other urea cycle disorders. "
3.	4-phenylbutyric acid (Buphenyl)FDA Link 01/01/2017 - "Analysis of the data indicated that this taste-masked formulation of sodium phenylbutyrate granules improved quality of life for urea-cycle disorder patients. " 01/01/2017 - "Several studies have reported the clinical experience of patients with urea-cycle disorders treated with this new tasteless formulation of sodium phenylbutyrate. " 02/08/2023 - "4-Phenylbutyrate (PB), which is used in the management of urea cycle disorders, has an unpleasant taste leading to poor patient compliance. " 01/01/2023 - "Taste-masked formulation of sodium phenylbutyrate (ACER-001) for the treatment of urea cycle disorders." 12/01/2021 - "Influence of food on pharmacokinetics and pharmacodynamics of 4-phenylbutyrate in patients with urea cycle disorders."
4.	glycerol phenylbutyrateIBA 01/01/2019 - "Long-term safety and efficacy of glycerol phenylbutyrate for the management of urea cycle disorder patients." 11/01/2017 - "Safety and efficacy of glycerol phenylbutyrate for management of urea cycle disorders in patients aged 2months to 2years." 01/01/2021 - "Glycerol phenylbutyrate efficacy and safety from an open label study in pediatric patients under 2 months of age with urea cycle disorders." 09/01/2015 - "Self-reported treatment-associated symptoms among patients with urea cycle disorders participating in glycerol phenylbutyrate clinical trials." 11/01/2023 - "Transition to glycerol phenylbutyrate for the management of urea cycle disorders: clinical experiences."
5.	Urea (Carbamide)FDA LinkGeneric 01/01/2017 - "Our studies provide proof-of-concept for gene-editing at the Arg1 locus and highlight the challenges that lie ahead to restore sufficient liver-based urea cycle function in patients with urea cycle disorders." 06/01/2022 - "The detection of urea is essential to monitor for identifying its pollution in the water, at the soil surface and in diagnosing urea cycle disorder related diseases. " 09/01/2019 - "Urea cycle disorders (UCDs) are rare inborn errors of urea synthesis. " 04/07/2015 - "Urea cycle disorders (UCDs) include a variety of genetic defects, which lead to inefficient urea synthesis. " 09/01/2014 - "Advances in urea cycle neuroimaging: Proceedings from the 4th International Symposium on urea cycle disorders, Barcelona, Spain, September 2013."
6.	NitrogenIBA 01/01/2021 - "Urea cycle disorders (UCD) are inherited defects in clearance of waste nitrogen with high morbidity and mortality. " 09/01/2015 - "While the introduction of nitrogen-scavenging medications has improved survival in patients with urea cycle disorders (UCDs), they are often associated with side effects that may affect patient compliance and outcomes. " 01/01/2017 - "Pharmacological treatment of urea-cycle disorders involves alternative nitrogen-scavenging pathways. " 01/01/2016 - "Phenylbutyrate is recommended in urea cycle disorders and liver injury to enhance nitrogen disposal by the urine. " 01/01/2016 - "Computational modeling to predict nitrogen balance during acute metabolic decompensation in patients with urea cycle disorders."
7.	Amino AcidsFDA Link 10/01/2011 - "Plasma amino acid analysis is very useful in revealing urea cycle disorders, and mutational analysis of the SLC25A13 gene can confirm the diagnosis." 11/01/2019 - "Evaluation of dietary treatment and amino acid supplementation in organic acidurias and urea-cycle disorders: On the basis of information from a European multicenter registry." 08/01/2019 - "Simultaneous quantification of 48 plasma amino acids by liquid chromatography-tandem mass spectrometry to investigate urea cycle disorders." 01/01/2018 - "Current newborn screening (NBS) for urea cycle disorders (UCD) is incomplete as only distal UCDs are included in most NBS programs by measuring elevated amino acid concentrations. " 05/31/2013 - "For amino acids playing a key role in commonly encountered amino acid and urea cycle disorders, a minimum critical resolution of 2.5 was pursued. "
8.	EnzymesIBA 07/01/2019 - "Further investigation with assistance from the genetics consult team revealed a partial enzyme deficiency associated with urea cycle disorder. " 07/01/2019 - "Urea cycle disorders are metabolic disorders of nitrogenous waste substances due to either complete or partial deficiency of enzymes. " 01/01/2018 - "Mutations in the gene coding for this enzyme are the most frequent cause of urea cycle disorders. " 04/01/2012 - "Urea cycle disorders encompass several enzyme deficiencies that can result in cerebral damage, with a wide clinical spectrum from asymptomatic to severe. " 03/01/2010 - "Late-onset urea cycle disorders caused by partial enzyme deficiencies may present with unexpected clinical phenotypes. "
9.	Arginine (L-Arginine)FDA Link 03/01/2012 - "Arginine hydrochloride is used in the evaluation of short stature and in the management of urea cycle disorders. " 11/15/2015 - "Using data from patients enrolled in a natural history study conducted by the Urea Cycle Disorders Consortium, we found that 97% of plasma arginine levels in subjects with arginase deficiency were above the normal range despite conventional treatment. " 04/01/2019 - "L-arginine was administered as a diagnostic treatment for urea cycle disorder (UCD) and serum ammonia, and her consciousness levels improved. " 01/01/2023 - "Arginase 1 Deficiency (ARG1-D) is a rare autosomal recessive urea cycle disorder (UCD) characterized by pathologic elevation of plasma arginine and debilitating manifestations. " 01/01/2019 - "Decreased plasma l-arginine levels in organic acidurias (MMA and PA) and decreased plasma branched-chain amino acid levels in urea cycle disorders as a potential cause of growth retardation: Options for treatment."
10.	Ligases (Synthetase)IBA 09/26/2023 - "Carbamoyl phosphate synthetase 1 (CPS1) deficiency is a severe urea cycle disorder. " 12/01/2022 - "Carbamoyl phosphate synthetase 1 (CPS1) deficiency is an autosomal recessive urea cycle disorder with varying presentations. " 09/07/2022 - "Carbamoyl phosphate synthetase deficiency (CPS1D) is a urea-cycle disorder (UCD). " 01/01/2022 - "Carbamoyl phosphate synthetase 1 deficiency (CPS1D) is a rare autosomal recessive urea cycle disorder characterized by hyperammonaemia. " 04/01/2020 - "Carbamoyl phosphate synthetase 1 deficiency (CPS1D) is a rare urea cycle disorder. "

Therapies and Procedures

1.	Therapeutics 01/01/2020 - "This study demonstrates the first proof-of-principle that sAAV-mediated therapy is a viable, potentially clinically translatable approach to CPS1 deficiency, a devastating urea cycle disorder." 09/01/2020 - "Thus, undiagnosed urea cycle disorders should be treated rapidly with acute therapy including NCG, which should be maintained until a genetic diagnosis is reached. " 11/01/2019 - "In 2012, we published guidelines summarizing and evaluating late 2011 evidence for diagnosis and therapy of urea cycle disorders (UCDs). " 10/01/2019 - "Progress and challenges in development of new therapies for urea cycle disorders." 01/01/2019 - "Impact of Diagnosis and Therapy on Cognitive Function in Urea Cycle Disorders."
2.	Renal Dialysis (Hemodialysis) 01/01/2013 - "Urea cycle disorder was suspected and hemodialysis was initiated. " 09/01/2008 - "Although the survival of patients who have urea cycle disorders has improved with the use of modalities such as alternative pathway therapy and hemodialysis, neurologic outcome is suboptimal. " 09/01/2012 - "Hemodialysis is often required for hyperammonemia in the organic acidemias and urea-cycle disorders. " 07/01/2019 - "A diagnosis of urea cycle disorder should be suspected in patients who have had a recent stressor with progressive lethargy and confusion associated with hyperammonemia, so that treatment may begin with intravenous sodium benzoate and phenylacetate initially and hemodialysis at 8 hours if ammonia levels do not decrease to avoid permanent neurologic damage."
3.	Liver Transplantation 11/01/2021 - "Role of liver transplantation in urea cycle disorders: Report from a nationwide study in Japan." 01/01/2023 - "Urea cycle disorders and indications for liver transplantation." 12/01/2021 - "Liver transplantation (LT) for children with urea cycle disorders (UCDs) is capable of correcting the enzymatic defect and preventing progressive neurologic injury. " 12/01/2021 - "Liver Transplantation in Children with Urea Cycle Disorders: The Importance of Minimizing Waiting Time." 10/01/2018 - "Early liver transplantation in neonatal-onset and moderate urea cycle disorders may lead to normal neurodevelopment."
4.	Bone Marrow Transplantation (Transplantation, Bone Marrow) 07/12/2023 - "Trending topics were osteoporosis, computed tomography, bone marrow transplantation in the early years of the study, chronic kidney disease, urea cycle disorders, next-generation sequencing, newborn screening, and familial hypercholesterolemia in the final years of the study. "
5.	Protein-Restricted Diet (Diet, Protein Restricted) 01/21/2022 - "Anthropometrics, Dietary Intake and Body Composition in Urea Cycle Disorders and Branched Chain Organic Acidemias: A Case Study of 18 Adults on Low-Protein Diets." 10/29/2020 - "Low-protein diets (LPDs) are the main treatment for urea cycle disorders (UCDs) and organic acidemias (OAs). " 10/29/2020 - "Nutrient Intake and Nutritional Status in Adult Patients with Inherited Metabolic Diseases Treated with Low-Protein Diets: A Review on Urea Cycle Disorders and Branched Chain Organic Acidemias." 01/01/2019 - "Patients with methylmalonic acidemia (MMA) and propionic acidemia (PA) and urea cycle disorders (UCD), treated with a protein restricted diet, are prone to growth failure. " 01/01/2020 - "Low protein diet and sodium or glycerol phenylbutyrate, two pillars of recommended long-term therapy of individuals with urea cycle disorders (UCDs), involve the risk of iatrogenic growth failure. "