Ornithine Carbamoyltransferase Deficiency Disease

An inherited urea cycle disorder associated with deficiency of the enzyme ORNITHINE CARBAMOYLTRANSFERASE, transmitted as an X-linked trait and featuring elevations of amino acids and ammonia in the serum. Clinical features, which are more prominent in males, include seizures, behavioral alterations, episodic vomiting, lethargy, and coma. (Menkes, Textbook of Child Neurology, 5th ed, pp49-50)

Also Known As:

Networked: 427 relevant articles (14 outcomes, 30 trials/studies)

Relationship Network

Disease Context: Research Results

Related Diseases

1.	Hyperammonemia
2.	Crigler-Najjar Syndrome (Syndrome, Crigler-Najjar)
3.	Brain Injuries (Brain Injury)
4.	Inborn Urea Cycle Disorders
5.	Citrullinemia

Experts

1.	Tuchman, Mendel: 8 articles (05/2015 - 02/2002)
2.	Lee, Brendan: 8 articles (09/2013 - 10/2003)
3.	Häberle, Johannes: 6 articles (11/2015 - 06/2003)
4.	Batshaw, Mark L: 6 articles (09/2013 - 01/2002)
5.	Nagasaka, Hironori: 6 articles (07/2013 - 08/2004)
6.	Gropman, Andrea L: 5 articles (09/2014 - 05/2008)
7.	Murayama, Kei: 5 articles (03/2012 - 08/2004)
8.	Scaglia, Fernando: 5 articles (01/2010 - 10/2003)
9.	Kobayashi, Kunihiko: 5 articles (03/2009 - 03/2004)
10.	Dhawan, Anil: 4 articles (10/2015 - 05/2004)

Drugs and Biologics

Drugs and Important Biological Agents (IBA) related to Ornithine Carbamoyltransferase Deficiency Disease:

1.	Ornithine Carbamoyltransferase (Ornithine Transcarbamylase)IBA 02/16/1996 - "A murine model of ornithine transcarbamylase (OTC) deficiency was used in this study to evaluate the efficacy of recombinant adenoviruses for correcting the metabolic defect in liver. " 06/10/2001 - "Mouse models of ornithine transcarbamylase (OTC) deficiency are being used to test the efficacy of viral vectors as possible vehicles for gene therapy. " 09/01/2013 - "A 66-year-old woman heterozygous for a mutation in the ornithine transcarbamylase gene (Otc) participated in a phase I gene therapy trial for OTC deficiency. " 05/01/2011 - "This study aimed at understanding clinical features, biochemistry and gene mutation in one Chinese pedigree which had a neonatal-onset ornithine transcarbamylase deficiency (OTCD) boy, and exploring the significance of ornithine transcarbamylase analysis in prenatal diagnosis. " 06/01/2009 - "For ornithine transcarbamylase (OTC) deficiency, in vitro studies have suggested the presence of dominant-negative effects, however, supporting in vivo studies have not been conducted. "
2.	Complementary DNA (cDNA)IBA 04/01/2000 - "This approach based on reverse transcription and nested PCR to obtain a double strand PBL OTC cDNA allowed the identification of genetic lesions in five Italian families affected by OTC deficiency (OTCD). " 02/01/1996 - "We have achieved significant improvement of ornithine transcarbamylase deficiency (OTCD) in a mouse model through adenoviral-mediated gene transfer of the human ornithine transcarbamylase cDNA. " 02/01/1991 - "Since the cloning of the cDNA for X-linked ornithine transcarbamylase (OTC) in 1984, diagnostic accuracy of OTC deficiency for prenatal and carrier detection has been greatly improved by the use of linkage analysis. " 06/01/1992 - "We analyzed DNA from 13 males with ornithine transcarbamylase (OTC) deficiency for gene deletions and known point mutations using the polymerase chain reaction (PCR), allelle-specific oligonucleotide (ASO) hybridization, and Southern blotting with full-length OTC cDNA and exon-specific probes. " 02/01/1986 - "Using a complementary DNA (cDNA) for OTC for Southern blot analysis of genomic DNA, we have found probands with complete OTC deficiency from two unrelated families in whom the same TaqI restriction endonuclease site has been altered because of independent, but not necessarily identical, mutations in the OTC gene, suggesting that this site may be a relative hotspot for mutation at a location that is critical for normal gene function. "
3.	Urea (Carbamide)FDA LinkGeneric 03/01/2015 - "Ornithine transcarbamylase deficiency (OTCD) is an X-linked disorder of metabolism of the urea cycle. " 09/25/2014 - "In addition, retrospective analysis of confirmed patients and presumptively normal newborn screening specimens suggests potential for the methods to identify patients with OTC deficiency, as well as other urea cycle defects. " 09/25/2014 - "Current newborn screening (NBS) protocols can detect several defects of the urea cycle, but screening for OTC deficiency remains a challenge due to the lack of a suitable assay. " 09/01/2014 - "Ornithine transcarbamylase deficiency (OTCD) is the most common type urea cycle enzyme deficiencies. " 07/01/2013 - "Characteristics of NO cycle coupling with urea cycle in non-hyperammonemic carriers of ornithine transcarbamylase deficiency."
4.	Arginine (L-Arginine)FDA Link 12/01/2008 - "When sufficient arginine is available after LPS stimulated net protein breakdown, NO production is unaffected by OTC deficiency." 12/01/2008 - "In response to LPS treatment (10 mg/kg ip), circulating arginine increased in all groups (P < 0.001), and NO production was no longer affected by the OTC deficiency due to increased net protein breakdown as a source for arginine. " 05/01/2008 - "The hyperammonemic encephalopathy was reversed by the infusion of arginine, a common treatment for hereditary OTC deficiency. " 01/01/1989 - "Ornithine transcarbamylase deficiency in a male: strict correlation between metabolic control and plasma arginine concentration." 09/01/1996 - "We describe a 12 year-old male patient with late-onset ornithine transcarbamylase deficiency, in whom infusion of arginine alone dramatically improved intercurrent hyperammonemia. "
5.	Messenger RNA (mRNA)IBA 07/01/2008 - "In patients with a strong suspicion of OTC deficiency despite normal results of sequencing exonic regions of the OTC gene, characterization of liver OTC mRNA is highly effective in resolving the genotype. " 07/01/2008 - "Analysis of mRNA transcripts improves the success rate of molecular genetic testing in OTC deficiency." 06/01/1991 - "We propose that these point mutations, which result in aberrant splicing of the OTC pre-mRNAs, lead to OTC deficiency through either decreased efficiency of mRNA export from the nucleus to the cytosol or synthesis of enzyme subunits that are unstable and rapidly degraded. " 08/14/1987 - "These results suggest that ornithine transcarbamylase deficiency in the spf-ash results from a mutation, which to some extent affects mRNA processing." 08/14/1987 - "Ornithine transcarbamylase deficiency in spf and spf-ash mice: genes, mRNAs and mRNA precursors."
6.	N-Methylaspartate (NMDA)IBA 09/01/1995 - "Reduced NMDA receptor densities in congenital OTC deficiency could represent an adaptive mechanism of protection against further excitotoxic brain injury." 03/01/2000 - "Possible mechanisms responsible for cholinergic neuronal loss in congenital OTC deficiency include decreased synthesis of the ChAT substrate acetyl CoA, impaired cerebral energy metabolism and NMDA receptor-mediated excitotoxicity. " 09/01/1995 - "In order to further elucidate the role of the glutamatergic neurotransmitter system in OTC deficiency, densities of binding sites for [3H]MK801, an NMDA receptor antagonist ligand were measured by quantitative receptor autoradiography in the brains of chronically hyperammonemic sparse-fur mice (spf), mutant mice with a congenital defect of OTC. " 01/01/1998 - "Possible mechanisms involved in the pathogenesis of cholinergic cell loss in congenital OTC deficiency include ammonia-induced inhibition of pyruvate and alpha-oxoglutarate oxidation, resulting in decreased synthesis of acetyl CoA and a cerebral energy deficit, as well as NMDA receptor-mediated excitotoxicity. "
7.	Factor VII (Proconvertin)IBA 01/01/2008 - "We reviewed the explant livers of seven children with metabolic disorders [ornithine-transcarbamylase deficiency (one), coagulation factor VII deficiency (three), Crigler-Najjar syndrome (one), progressive familial intrahepatic cholestasis type 2 (PFIC-2) deficiency (two)] who received allograft hepatocytes by intraportal infusion with improvement in phenotype, although all later underwent liver transplantation (LT). "
8.	progressive familial intrahepatic 1 CholestasisIBA 01/01/2008 - "We reviewed the explant livers of seven children with metabolic disorders [ornithine-transcarbamylase deficiency (one), coagulation factor VII deficiency (three), Crigler-Najjar syndrome (one), progressive familial intrahepatic cholestasis type 2 (PFIC-2) deficiency (two)] who received allograft hepatocytes by intraportal infusion with improvement in phenotype, although all later underwent liver transplantation (LT). "
9.	AmmoniaIBA 01/01/2007 - "Twelve neonates with elevated serum ammonia levels, confirmed through urine organic acid analysis and serum amino acid studies, were documented to have OTC deficiency. " 11/01/2000 - "Three male neonates with elevated serum ammonia levels were shown, based on urine organic acid analysis and serum amino acid studies, to have OTC deficiency. " 08/01/1999 - "A second infant presented at 3 days of age with a similar history, blood ammonia of 1382 micromol/L, and metabolic studies indicative of ornithine transcarbamylase deficiency. " 08/31/1983 - "Study of ammonia metabolism in a patient with ornithine transcarbamylase deficiency using an 15N tracer." 11/01/2013 - "The authors reported a successful CVVH using umbilical vein as a vascular access site for ammonia removal in a neonate with OTC deficiency with progressive elevation of plasma ammonia. "
10.	Branched-Chain Amino AcidsIBA 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 - "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. " 10/01/2007 - "Therapeutic goals for OTC deficiency are to maintain plasma ammonia<80 micromol/L, plasma glutamine<1,000 micromol/L, argininemia 80-150 micromol/L and branched chain amino acids within the normal range, in order to prevent episodes of potentially lethal acute hyperammonemia. " 01/01/2013 - "There was a strong positive correlation between low plasma branched-chain amino acids and other essential amino acids, and a negative correlation between ammonia and phenylalanine to tyrosine (Phe:Tyr) ratio in patients with OTC deficiency, and between glutamine and Phe:Tyr ratio in all patients, indicating protein deficiency. "

Therapies and Procedures

1.	Liver Transplantation 09/01/1997 - "Liver transplantation is effective in many patients and recent experimental studies using adenoviral vectors suggest that gene therapy may ultimately be useful in the treatment of congenital OTC deficiency." 01/01/2005 - "We report the case of a 7-year-old girl with ornithine transcarbamylase deficiency whose quality of life (QOL) improved greatly after a living donor liver transplantation (LDLT). " 01/01/2005 - "Improved quality of life and unchanged magnetic resonance brain imaging after living donor liver transplantation for late-onset ornithine transcarbamylase deficiency: report of a case." 09/14/1996 - "Histological improvement in native liver after auxiliary partial liver transplantation for ornithine transcarbamylase deficiency." 09/01/1998 - "The purpose of this study was to combine our clinical experience with a review of the literature to determine the value of orthotopic liver transplantation in the treatment of both boys and girls with ornithine transcarbamylase deficiency. "
2.	Transplantation (Transplant Recipients) 12/01/2009 - "First example of hepatocyte transplantation to alleviate ornithine transcarbamylase deficiency, monitored by NMR-based metabonomics." 09/16/1999 - "Death after transplantation of a liver from a donor with unrecognized ornithine transcarbamylase deficiency." 01/01/1993 - "We have studied hepatocyte transplantation as alternative therapy in spfash mouse, the animal mode of OTC deficiency. " 01/01/1993 - "[Intrasplenic transplantation of hepatocytes in spf-ash mice with congenital ornithine transcarbamylase deficiency]." 02/01/2008 - "Hepatocyte transplantation followed by auxiliary liver transplantation--a novel treatment for ornithine transcarbamylase deficiency."
3.	Transplants (Transplant) 10/01/2008 - "One patient with OTC deficiency has had a liver transplant. " 05/01/2005 - "A boy with OTC deficiency who received a partial liver transplant from his mother showed normal general condition for two years. " 10/15/1998 - "We have estimated that the minimum volume of normal liver required to correct the metabolic defect in ornithine transcarbamylase deficiency is 8 cm3/kg. The ligation of the right portal branch was a safe and effective method of inducing a gradual and progressive involution of the hypertrophic native liver and regeneration of the atrophic graft." 03/01/2014 - "Hepatocyte transplantation using a living donor reduced graft in a baby with ornithine transcarbamylase deficiency: a novel source of hepatocytes." 04/15/1997 - "Coexistence of a graft with the preserved native liver in auxiliary partial orthotopic liver transplantation from a living donor for ornithine transcarbamylase deficiency."
4.	Homologous Transplantation (Allograft) 08/01/1999 - "Severe late acute allograft rejection in a child after living-related auxiliary partial orthotopic liver transplantation for ornithine transcarbamylase deficiency." 01/01/2008 - "We reviewed the explant livers of seven children with metabolic disorders [ornithine-transcarbamylase deficiency (one), coagulation factor VII deficiency (three), Crigler-Najjar syndrome (one), progressive familial intrahepatic cholestasis type 2 (PFIC-2) deficiency (two)] who received allograft hepatocytes by intraportal infusion with improvement in phenotype, although all later underwent liver transplantation (LT). "
5.	Ligation 10/15/1998 - "We have estimated that the minimum volume of normal liver required to correct the metabolic defect in ornithine transcarbamylase deficiency is 8 cm3/kg. The ligation of the right portal branch was a safe and effective method of inducing a gradual and progressive involution of the hypertrophic native liver and regeneration of the atrophic graft."