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: 257 relevant articles (4 outcomes, 18 trials/studies)

Relationship Network

Disease Context: Research Results

Related Diseases

1.	Ornithine Carbamoyltransferase Deficiency Disease
2.	Neoplasms (Cancer)
3.	Cystic Fibrosis (Mucoviscidosis)
4.	Hemoglobinopathies
5.	Hyperammonemia

Experts

1.	Lee, Brendan: 18 articles (07/2015 - 12/2002)
2.	Häberle, Johannes: 11 articles (09/2015 - 10/2002)
3.	Diaz, George A: 8 articles (09/2015 - 08/2008)
4.	Berry, Susan A: 7 articles (09/2015 - 05/2007)
5.	Lichter-Konecki, Uta: 7 articles (09/2015 - 08/2008)
6.	Mokhtarani, Masoud: 7 articles (09/2015 - 06/2010)
7.	Smith, Wendy: 7 articles (09/2015 - 10/2005)
8.	Scharschmidt, Bruce F: 7 articles (09/2015 - 06/2010)
9.	Nagamani, Sandesh C S: 6 articles (11/2015 - 05/2012)
10.	Sun, Qin: 5 articles (11/2015 - 02/2011)

Drugs and Biologics

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

1.	SodiumIBA 09/01/2014 - "Sodium phenylbutyrate (NaPBA) is a commonly used medication for the treatment of patients with urea cycle disorders (UCDs). " 05/01/2014 - "Sodium phenylbutyrate (NaPB) is an orally bioavailable small molecule approved by the FDA for treatment of urea-cycle disorders. " 12/01/2012 - "Sodium phenylbutyrate (NaPB) is used as a treatment for urea cycle disorders (UCD). " 04/01/1998 - "Sodium phenylbutyrate (NaPB) is used in urea cycle disorders. " 01/01/1995 - "Sodium phenylbutyrate (SPB), an oral agent used to treat individuals with urea-cycle disorders, has been shown to increase HbF in nonanemic individuals and in individuals with sickle cell disease. "
2.	Urea (Carbamide)FDA LinkGeneric 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." 04/01/2006 - "Mouse models for urea cycle disorders have been available for the past 30 y; however, until now, no measurements of urea production in vivo have been conducted. " 01/01/2001 - "A survey was sent to the American members of the National Urea Cycle Disorders Foundation to ascertain the types and extent of stress imposed on families who have a child with a urea cycle defect. " 11/01/2000 - "This article addresses the function of the urea cycle and the diagnosis and management of urea cycle disorders."
3.	NitrogenIBA 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. " 11/19/2015 - "A decrease in nitrogen flux through ASS1 in the liver causes the urea cycle disorder citrullinaemia. " 06/01/2011 - "Phenylbutyrate is a drug used in patients with urea cycle disorder to elicit alternative pathways for nitrogen disposal. " 01/01/2015 - "Argininosuccinate lyase deficiency (ASLD) is a urea cycle disorder (UCD) treated with dietary adjustment and nitrogen scavenging agents. " 02/01/2013 - "Its supplementation is likely to be used in conditions like erectile dysfunction, sickle cell anemia, short bowel syndrome (to restore nitrogen balance), hyperlipidemia, cancer chemotherapy, hypercholestremia, in hyperoxic lung damage, urea cycle disorders, Alzheimers disease, multi-infarct dementia and as an immunomodulator. "
4.	EnzymesIBA 02/01/2008 - "In this paper, selected old and new biochemical findings in PKU, urea cycle disorders and nonketotic hyperglycinaemia are reviewed; the aim is to show that integrating the knowledge gained in the last decades on enzymes and transporters related to amino acid metabolism allows a more extensive interpretation of biochemical results obtained for diagnosis and follow-up of patients and may help to pose new questions and to avoid pitfalls. " 06/01/2006 - "A deficiency in any of the five classical enzymes of the pathway causes a urea cycle disorder. " 02/01/2014 - "Urea cycle disorders (UCDs) are caused by loss of function in any of the enzymes responsible for ureagenesis, and are characterized by life-threatening episodes of acute metabolic decompensation with hyperammonemia (HA). " 05/01/2012 - "Deficiencies of any of these enzymes of the cycle result in urea cycle disorders (UCDs), a group of inborn errors of hepatic metabolism that often result in life-threatening hyperammonemia. " 02/15/2011 - "Deficiencies of any of these enzymes of the cycle result in urea cycle disorders (UCD), a group of inborn errors of hepatic metabolism that often result in life threatening hyperammonemia. "
5.	Sodium BenzoateFDA Link 03/01/2005 - "Sodium benzoate (SB) is a chemical substance that is used for preparing food and drinks and in the treatment of some metabolic (urea cycle disorders and hepatic coma) diseases. " 07/01/2007 - "This study explores a novel use of sodium benzoate (NaB), a commonly used food additive and a Food and Drug Administration-approved nontoxic drug for urea cycle disorders, in treating the disease process of relapsing-remitting EAE in female SJL/J mice. " 12/01/2011 - "Sodium benzoate (NaB), a metabolite of cinnamon and a FDA-approved drug against urea cycle disorders in children, is a widely used food additive, which is long known for its microbicidal effect. " 03/01/2000 - "Intravenous sodium benzoate and sodium phenylacetate have been used successfully in the treatment of acute hyperammonaemia in patients with urea cycle disorders. " 05/31/2007 - "We report the results of a 25-year, open-label, uncontrolled study of sodium phenylacetate and sodium benzoate therapy (Ammonul, Ucyclyd Pharma) in 299 patients with urea-cycle disorders in whom there were 1181 episodes of acute hyperammonemia. "
6.	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. " 03/01/2010 - "The authors recommend that unexplained or nonresponsive neuropsychiatric/neurodevelopmental symptoms appearing during childhood or adolescence be followed by a study of ammonia and amino acid plasmatic levels to rule out a urea cycle disorder." 07/01/2015 - "Fasting ammonia correlates strongly and positively with daily ammonia exposure and with the risk and rate of hyperammonemic crises, suggesting that patients with urea cycle disorder may benefit from tight ammonia control." 07/01/2015 - "The relationships between fasting ammonia, daily ammonia exposure, and hyperammonemic crises were analyzed in >100 patients with urea cycle disorders. " 05/08/2015 - "He was found to have elevated ammonia level as well as orotic aciduria; results consistent with a urea cycle disorder. "
7.	phenylacetic acid (phenylacetate)FDA Link 04/01/2003 - "The present study underlines the importance of sodium phenylacetate (NaPA), a drug approved for urea cycle disorders, in inhibiting the disease process of adoptively transferred EAE in female SJL/J mice at multiple steps. " 12/01/2013 - "Elevated phenylacetic acid levels do not correlate with adverse events in patients with urea cycle disorders or hepatic encephalopathy and can be predicted based on the plasma PAA to PAGN ratio." 09/01/2000 - "Phenylacetate ingestion has been used to probe Krebs cycle metabolism and to augment waste nitrogen excretion in urea cycle disorders. " 03/01/2000 - "Intravenous sodium benzoate and sodium phenylacetate have been used successfully in the treatment of acute hyperammonaemia in patients with urea cycle disorders. " 05/31/2007 - "Survival after treatment with phenylacetate and benzoate for urea-cycle disorders."
8.	Branched-Chain Amino AcidsIBA 04/01/2004 - "Our studies suggest that this therapeutic modality has a substantial impact on the metabolism of branched chain amino acids in urea cycle disorder patients. " 04/01/2004 - "We have measured steady state plasma branched chain and other essential non-branched chain amino acids in control subjects, untreated ornithine transcarbamylase deficiency females and treated null activity urea cycle disorder patients in the fed steady state during the course of stable isotope studies. " 01/01/2010 - "These studies suggested that alternative pathway therapy with sodium phenylbutyrate causes a substantial impact on the metabolism of branched chain amino acids in patients with urea cycle disorders, implying that better titration of protein restriction can be achieved with branched chain amino acid supplementation in these patients who are on alternative pathway therapy." 09/01/2014 - "Sodium phenylbutyrate decreases plasma branched-chain amino acids in patients with urea cycle disorders." 01/01/2010 - "Plasma branched chain amino acids and other essential amino acids were measured in control subjects, untreated ornithine transcarbamylase deficiency females, and treated patients with urea cycle disorders (ornithine transcarbamylase deficiency and argininosuccinate synthetase deficiency) in the absorptive state during the course of stable isotope studies. "
9.	Ornithine Carbamoyltransferase (Ornithine Transcarbamylase)IBA 07/24/1987 - "The ornithine transcarbamylase-deficient sparse fur mouse is an excellent model to study the most common human urea cycle disorder. " 08/01/2003 - "Despite the apparent functional ablation of ORNT1 in 10 French-Canadian probands with the ORNT1-F188 Delta allele, these patients are mildly affected when compared to patients with other urea cycle disorders such as deficiency of ornithine transcarbamylase. " 01/01/2002 - "Ornithine carbamoyltransferase (OCT) deficiency is the commonest of the inherited urea cycle disorders. " 01/01/1998 - "Ornithine transcarbamylase (OTCase) deficiency, the most common inherited urea cycle disorder, is transmitted as an X-linked trait. " 09/15/2013 - "Ornithine transcarbamylase (OTC) deficiency is the most common urea cycle disorder and demonstrates X-linked inheritance. "
10.	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. " 01/01/2010 - "In the case of the other urea cycle disorders, arginine levels are markedly decreased unless the patients are supplemented with this amino acid. " 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. " 01/01/2010 - "Creatine metabolism is of importance to patients with urea cycle disorders in two ways, both related to arginine levels. " 07/19/1978 - "The therapeutic effect of supplying ornithine and arginine (an essential amino acid in urea cycle disorders) is described. "

Therapies and Procedures

1.	Renal Dialysis (Hemodialysis) 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. " 01/01/2013 - "Urea cycle disorder was suspected and hemodialysis was initiated. " 09/01/2012 - "Hemodialysis is often required for hyperammonemia in the organic acidemias and urea-cycle disorders. "
2.	Liver Transplantation 10/01/2015 - "Liver Transplantation for Urea Cycle Disorders: Analysis of the United Network for Organ Sharing Database." 02/01/2015 - "A retrospective analysis was performed on the occurrence of disease, operation and the follow-up post liver transplantation in 4 patients with urea cycle disorders who underwent liver transplantation during June 2001 to May 2014. " 01/01/2014 - "Decision making concerning liver transplantation is unique for children with urea cycle disorders (UCDs) and organic acidemias (OAs) because of their immediate high priority on the waiting list, which is not related to the severity of their disease. " 01/01/2014 - "Pediatric liver transplantation for urea cycle disorders and organic acidemias: United Network for Organ Sharing data for 2002-2012." 03/01/2013 - "Liver transplantation for urea cycle disorders in pediatric patients: a single-center experience."
3.	Transplantation (Transplant Recipients) 08/01/2015 - "Neurologic outcome of urea cycle disorder liver transplant recipients may be predicted by pretransplant neurological imaging." 06/01/2003 - "Isolated hepatocyte transplantation in an infant with a severe urea cycle disorder." 08/01/2005 - "Liver cell transplantation was performed in a child with urea cycle disorder poorly equilibrated by conventional therapy as a bridge to transplantation. "
4.	Protein-Restricted Diet (Diet, Protein Restricted) 10/01/2007 - "Regimens applicable in adult neurology include low protein diet (phenylketonuria, homocystinuria, urea cycle disorders, organic acidurias), low fatty acid diets (fatty acid B oxidation defects, adrenomyeloneuropathy, Refsum's disease) and ketogenic diet (pyruvate dehydrogenase deficiency, glucose transporter (GLUT1) deficiency, refractory epilepsy). " 12/01/1999 - "Although this retrospective series is not really representative of the modern treatment combining low protein diet and arginine, sodium benzoate and sodium phenylbutyrate, it is obvious that the long-term outcome of all urea cycle disorders remains very guarded. "
5.	Peritoneal Dialysis 07/01/2014 - "Six neonates with hyperammonemic coma (four with organic acidemias, two with urea cycle disorders) and three with leucine accumulation due to maple syrup urine disease (MSUD) were managed with peritoneal dialysis in conjunction with dietary and pharmacological therapy. " 04/01/1999 - "We report our experience with continuous venovenous haemodialysis (CVVHD) in six neonates with hyperammonaemic coma due to urea-cycle disorders or propionic acidaemia and in one child with leucine accumulation due to maple-syrup urine disease (MSUD), in comparison with five patients managed by peritoneal dialysis (PD) (2 hyperammonaemia, 3 MSUD). "