ornithine carbamoyltransferase deficiency disease

Summary

Summary: An inherited urea cycle disorder associated with deficiency of the enzyme ORNITHINE CARBAMOYLTRANSFERASE, transmitted as a sex-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)

Top Publications

  1. ncbi Analysis of tumors arising in male B6C3F1 mice with and without AAV vector delivery to liver
    Peter Bell
    Gene Therapy Program, Division of Medical Genetics, Department of Medicine, Hospital of the University of Pennsylvania, University of Pennsylvania, Philadelphia, PA 19104, USA
    Mol Ther 14:34-44. 2006
  2. ncbi Long-term correction of ammonia metabolism and prolonged survival in ornithine transcarbamylase-deficient mice following liver-directed treatment with adeno-associated viral vectors
    David Moscioni
    Gene Therapy Program, Division of Medical Genetics, Department of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA
    Mol Ther 14:25-33. 2006
  3. ncbi Fatal systemic inflammatory response syndrome in a ornithine transcarbamylase deficient patient following adenoviral gene transfer
    Steven E Raper
    Department of Surgery, University of Pennsylvania School of Medicine, BRB II III Rm, 607 421 Curie Blvd, Philadelphia, PA 19104, USA
    Mol Genet Metab 80:148-58. 2003
  4. ncbi Ornithine transcarbamylase deficiency: a urea cycle defect
    Neil Gordon
    Wilmslow, UK
    Eur J Paediatr Neurol 7:115-21. 2003
  5. pmc AAV2/8-mediated correction of OTC deficiency is robust in adult but not neonatal Spf(ash) mice
    Sharon C Cunningham
    Gene Therapy Research Unit, Children s Medical Research Institute and The Children s Hospital at Westmead, Wentworthville, New South Wales, Australia
    Mol Ther 17:1340-6. 2009
  6. ncbi Mutations and polymorphisms in the human ornithine transcarbamylase (OTC) gene
    Saori Yamaguchi
    College of Life Science, University of Maryland, College Park, Maryland, USA
    Hum Mutat 27:626-32. 2006
  7. ncbi First specific preimplantation genetic diagnosis for ornithine transcarbamylase deficiency
    P F Ray
    Département de génétique et unité U393, Hopital Necker Enfants Malades, 75743 Paris Cedex 15, France
    Prenat Diagn 20:1048-54. 2000
  8. ncbi Mutations and polymorphisms in the human ornithine transcarbamylase gene
    Mendel Tuchman
    Children s Research Institute, Children s National Medical Center, George Washington University, Washington DC, USA
    Hum Mutat 19:93-107. 2002
  9. ncbi Long-term correction of ornithine transcarbamylase deficiency by WPRE-mediated overexpression using a helper-dependent adenovirus
    Asad Mian
    Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA
    Mol Ther 10:492-9. 2004
  10. ncbi The molecular basis of ornithine transcarbamylase deficiency
    M Tuchman
    Children s Research Institute, Children s National Medical Center, Washington, DC 20010 2970, USA
    Eur J Pediatr 159:S196-8. 2000

Detail Information

Publications175 found, 100 shown here

  1. ncbi Analysis of tumors arising in male B6C3F1 mice with and without AAV vector delivery to liver
    Peter Bell
    Gene Therapy Program, Division of Medical Genetics, Department of Medicine, Hospital of the University of Pennsylvania, University of Pennsylvania, Philadelphia, PA 19104, USA
    Mol Ther 14:34-44. 2006
    ..It appears that AAV vectors alone do not contribute to the formation of tumors in these strains of mice although the expression of LacZ alone or in combination with vector may be problematic...
  2. ncbi Long-term correction of ammonia metabolism and prolonged survival in ornithine transcarbamylase-deficient mice following liver-directed treatment with adeno-associated viral vectors
    David Moscioni
    Gene Therapy Program, Division of Medical Genetics, Department of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA
    Mol Ther 14:25-33. 2006
    ..Numerous mice, representative of all treatment groups followed for +250 days, were observed to have either nodules or discrete tumors in the liver, the etiology of which is the subject of a companion paper...
  3. ncbi Fatal systemic inflammatory response syndrome in a ornithine transcarbamylase deficient patient following adenoviral gene transfer
    Steven E Raper
    Department of Surgery, University of Pennsylvania School of Medicine, BRB II III Rm, 607 421 Curie Blvd, Philadelphia, PA 19104, USA
    Mol Genet Metab 80:148-58. 2003
    ....
  4. ncbi Ornithine transcarbamylase deficiency: a urea cycle defect
    Neil Gordon
    Wilmslow, UK
    Eur J Paediatr Neurol 7:115-21. 2003
    ..Liver transplant can be considered when symptoms are life-threatening, although there may be severe complications.Gene replacement therapy is the hope of the future...
  5. pmc AAV2/8-mediated correction of OTC deficiency is robust in adult but not neonatal Spf(ash) mice
    Sharon C Cunningham
    Gene Therapy Research Unit, Children s Medical Research Institute and The Children s Hospital at Westmead, Wentworthville, New South Wales, Australia
    Mol Ther 17:1340-6. 2009
    ..This loss of expression in the neonatal liver is the consequence of hepatocellular proliferation and presents an added challenge to human therapy...
  6. ncbi Mutations and polymorphisms in the human ornithine transcarbamylase (OTC) gene
    Saori Yamaguchi
    College of Life Science, University of Maryland, College Park, Maryland, USA
    Hum Mutat 27:626-32. 2006
    ..5% of the genomic sequence. In addition, a phenocopy of OTC deficiency caused by mutations in another unknown gene cannot be excluded...
  7. ncbi First specific preimplantation genetic diagnosis for ornithine transcarbamylase deficiency
    P F Ray
    Département de génétique et unité U393, Hopital Necker Enfants Malades, 75743 Paris Cedex 15, France
    Prenat Diagn 20:1048-54. 2000
    ..The second cycle resulted in the birth of a baby boy devoid of the OTC mutation. This constitutes the first birth following PGD carried out by a French team...
  8. ncbi Mutations and polymorphisms in the human ornithine transcarbamylase gene
    Mendel Tuchman
    Children s Research Institute, Children s National Medical Center, George Washington University, Washington DC, USA
    Hum Mutat 19:93-107. 2002
    ..Even with sequencing of the entire reading frame and exon/intron boundaries, only about 80% of the mutations are detected in patients with proven OTC deficiency. The remaining probably occur within the introns or in regulatory domains...
  9. ncbi Long-term correction of ornithine transcarbamylase deficiency by WPRE-mediated overexpression using a helper-dependent adenovirus
    Asad Mian
    Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA
    Mol Ther 10:492-9. 2004
    ..These data represent an important approach for treating human inborn errors of hepatocyte metabolism like the UCDs that require high-level transduction and gene expression for clinical correction...
  10. ncbi The molecular basis of ornithine transcarbamylase deficiency
    M Tuchman
    Children s Research Institute, Children s National Medical Center, Washington, DC 20010 2970, USA
    Eur J Pediatr 159:S196-8. 2000
    ..Several symptomatic and asymptomatic adults have now been identified to have deleterious mutations in the OTC gene leading to predisposition to hyperammonemia...
  11. ncbi Genetic analysis in nine unrelated Italian patients affected by OTC deficiency: detection of novel mutations in the OTC gene
    S Bisanzi
    Neurometabolic Unit, Department of Pediatrics, University of Florence, Meyer Children s Hospital, Via Luca Giordano 13, Italy
    Mol Genet Metab 76:137-44. 2002
    ..This insertion causes a frame shift in OTC cDNA ORF and leads to a premature stop codon. The previously described mutations N161S, R141Q, T178M, R92X, A208T, M268T were identified in the other six manifesting carriers...
  12. ncbi Identification of new mutations in the ornithine transcarbamylase (OTC) gene in Korean families
    H W Yoo
    Department of Pediatrics, Asan Medical Center, Asan Life Science Research Institute, Ulsan University College of Medicine, Seoul, Korea
    J Inherit Metab Dis 19:31-42. 1996
    ..This missense mutation has been described previously and is known to eliminate a TaqI recognition site in exon 5...
  13. ncbi Identification of novel mutations in the human ornithine transcarbamylase (OTC) gene of Korean patients with OTC deficiency and transient expression of the mutant proteins in vitro
    Gu Hwan Kim
    Medical Genetics Clinics and Laboratory, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Korea
    Hum Mutat 27:1159. 2006
    ..853delC, and c.796-805del. All the novel mutations in this study were tested in 100 normal alleles. In vitro expression study of some of novel missense mutations elucidated the correlation of genotype and phenotype of the OTC deficiency...
  14. ncbi Evidence for mutational cis-acting factors affecting mutagenesis in the ornithine transcarbamylase gene
    Luisa Azevedo
    IPATIMUP, Porto, Portugal
    Hum Mutat 24:273. 2004
    ..89-61.5, p=1.5 x 10(-5)). Since most of pathogenic OTC mutations are short-lived or de novo, these findings strongly support the hypothesis that a specific haplotypic background confers a higher risk for mutation occurrence at this locus...
  15. ncbi Developmental outcomes with early orthotopic liver transplantation for infants with neonatal-onset urea cycle defects and a female patient with late-onset ornithine transcarbamylase deficiency
    Kim L McBride
    Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas, USA
    Pediatrics 114:e523-6. 2004
    ..We conclude that early liver transplantation and aggressive metabolic management improve early neurologic outcomes for children with UCDs, but longer follow-up monitoring is needed...
  16. ncbi Clinical onset and prognosis of Asian children with organic acidemias, as detected by analysis of urinary organic acids using GC/MS, instead of mass screening
    Daisuke Hori
    Department of Pediatrics, Faculty of Medicine, Shimane University, 89 1 En ya cho, Izumo, Shimane 693 8501, Japan
    Brain Dev 27:39-45. 2005
    ..We concluded that detection of such patients at the presymptomatic stages using newborn mass screening is essential for prognosis improvement with OAs...
  17. ncbi Urinary uracil in female patients with ornithine transcarbamylase deficiency
    Satoshi Sumi
    Department of Pediatrics, Neonatology and Congenital Disorders, Graduate School of Medical Sciences, Nagoya City University, Nagoya, Japan
    Pediatr Int 47:262-6. 2005
    ..It is important to establish a simple method to distinguish symptomatic from asymptomatic patients...
  18. ncbi Intermittent hyperammonemic encephalopathy in a child with ornithine transcarbamylase deficiency
    Sheffali Gulati
    Department of Pediatrics, All India Institute of Medical Sciences, New Delhi, India
    Indian J Pediatr 71:645-7. 2004
    ..The authors report a heterozygous female with OTC deficiency who presented with recurrent encephalopathy...
  19. ncbi A suspected case of ornithine transcarbamylase deficiency in a cat
    Tsukimi Washizu
    Department of Clinical Pathology, Nippon Veterinary and Animal Science University, Tokyo, Japan
    J Vet Med Sci 66:701-3. 2004
    ..A presumptive diagnosis of ornithine transcarbamylase deficiency was made on the basis of the detection of orotic acid and uracil...
  20. ncbi [Molecular characterization of a new mutation E122G of human ornithine transcarbamylase gene]
    Hua Gao
    Da An Gene Diagnostic Center, Sun Yat Sen University, Guangzhou, Guangdong, PR China
    Zhonghua Yi Xue Yi Chuan Xue Za Zhi 20:19-22. 2003
    ..To determine the molecular basis of late onset ornithine transcarbamylase (OTC) deficiency in a Chinese family of Han nationality and the exon sequences of OTC gene of this patient...
  21. ncbi Biotechnology and clinical trials
    Jay P Siegel
    Office of Therapeutics Research and Review, Center for Biologics Evaluation and Research, US Food and Drug Administration, Rockville, Maryland 20852, USA
    J Infect Dis 185:S52-7. 2002
    ....
  22. ncbi Ornithine transcarbamylase deficiency: a novel splice site mutation in a family with meiotic recombination and a new useful SNP for diagnosis
    Luisa Azevedo
    IPA TIMUP, Porto, Portugal
    Mol Genet Metab 76:68-70. 2002
    ....
  23. ncbi An unusual clinical and biochemical presentation of ornithine transcarbamylase deficiency in a male patient
    A B Burlina
    Metabolic Unit, Department of Pediatrics, Azienda Ospedale, Universita di Padova, Via Giustiniani 3, 35128, Padua, Italy
    J Inherit Metab Dis 29:179-81. 2006
    ..Ornithine transcarbamylase deficiency was diagnosed after detecting elevated urinary orotate concentrations in a sample collected just before death, and the diagnosis was confirmed by DNA analysis...
  24. ncbi Identification of seven novel missense mutations, two splice-site mutations, two microdeletions and a polymorphic amino acid substitution in the gene for ornithine transcarbamylase (OTC) in patients with OTC deficiency
    Consuelo Climent
    Instituto de Biomedicina de Valencia CSIC, Spain
    Hum Mutat 19:185-6. 2002
    ..This mutation coexisted in a female patient with the change T333A that appears to be a previously unreported polymorphism. The three male patients but only four of the eight female patients inherited the mutation...
  25. ncbi A pilot study of in vivo liver-directed gene transfer with an adenoviral vector in partial ornithine transcarbamylase deficiency
    Steven E Raper
    Institute for Human Gene Therapy and Department of Surgery, University of Pennsylvania, Philadelphia, PA 19104, USA
    Hum Gene Ther 13:163-75. 2002
    ..The low levels of gene transfer detected in this trial suggest that at the doses tested, significant metabolic correction did not occur...
  26. ncbi Complete recovery from acute encephalopathy of late-onset ornithine transcarbamylase deficiency in a 3-year-old boy
    C M Mak
    Division of Clinical Biochemistry, Queen Mary Hospital, Hong Kong, SAR, China
    J Inherit Metab Dis 30:981. 2007
    ..Therefore, a high clinical suspicion is a key to correct and timely diagnosis, especially in those patients with atypical presentations...
  27. ncbi Successful living-donor liver transplantation from an asymptomatic carrier mother in ornithine transcarbamylase deficiency
    H Nagasaka
    Department of Pediatrics, Hokkaido University School of Medicine, Sapporo, Japan
    J Pediatr 138:432-4. 2001
    ..One-year monitoring of plasma amino acid and urinary orotate/orotidine levels revealed no abnormality in the urea cycle in either subject...
  28. ncbi Cognitive outcome in urea cycle disorders
    Andrea L Gropman
    Children s Research Institute, Children s National Medical Center, Department of Pediatrics, George Washington University School of Medicine and Health Sciences, Washington, DC 20010 2916, USA
    Mol Genet Metab 81:S58-62. 2004
    ..Such methods of investigation may serve as a model for studying the relationship between genes, biochemical markers, brain function, and behavior in other metabolic diseases...
  29. ncbi How reliable is the allopurinol load in detecting carriers for ornithine transcarbamylase deficiency?
    S Grunewald
    Institute of Child Health, London, UK
    J Inherit Metab Dis 27:179-86. 2004
    ..In the absence of other supportive evidence, confirmation by mutation analysis is required...
  30. ncbi Unmasked adult-onset urea cycle disorders in the critical care setting
    Marshall L Summar
    Center for Human Genetic Research, Division of Medical Genetics, Department of Pediatrics, Vanderbilt University Medical Center, Nashville, TN 37232 0165, USA
    Crit Care Clin 21:S1-8. 2005
    ..Comorbid conditions such as physical trauma often delay the diagnosis of the urea cycle defect. Prompt recognition and treatment are essential in determining the outcome of these patients...
  31. ncbi Urea cycle disorders: clinical presentation outside the newborn period
    Wendy Smith
    Maine Pediatric Specialty Group, Portland, ME 04102, USA
    Crit Care Clin 21:S9-17. 2005
    ..Treatment with dietary protein restriction and medications may be challenging in children...
  32. ncbi Current role of liver transplantation for the treatment of urea cycle disorders: a review of the worldwide English literature and 13 cases at Kyoto University
    Daisuke Morioka
    Organ Transplant Unit, Kyoto University Hospital, Kyoto, Japan
    Liver Transpl 11:1332-42. 2005
    ..In conclusion, LT should be considered to be the definitive treatment for UCDs at this stage, although some issues remain unresolved...
  33. ncbi [A newborn infant with hyperventilation]
    Rolf Lindemann
    Intensivavdelingen for nyfødte, Barneklinikken, Ulleval universitetssykehus, 0407 Oslo
    Tidsskr Nor Laegeforen 128:1535-6. 2008
    ..67C >T (p.R23X), a known mutation leading to urea cycle disorder (OTC). It is important to detect carriers among older siblings and to inform the parents of the possibility of prenatal diagnostics...
  34. ncbi n of 1 trial for an ornithine transcarbamylase deficiency carrier
    A Hackett
    Hunter Genetics, P O Box 84, Waratah, Newcastle, NSW 2298, Australia University of Newcastle, NSW, Australia
    Mol Genet Metab 94:157-61. 2008
    ..We propose that other rare metabolic conditions may be amenable to such trials, if the benefit of treatment is in doubt...
  35. ncbi Interaction between murine spf-ash mutation and genetic background yields different metabolic phenotypes
    Juan C Marini
    USDA ARS Children s Nutrition Research Center, Department of Pediatrics, Baylor College of Medicine, Houston, Texas, USA
    Am J Physiol Endocrinol Metab 293:E1764-71. 2007
    ..These observations help explain the wide phenotypic variation of ornithine transcarbamylase deficiency in the human population...
  36. ncbi Aminograms during continuous hemodiafiltration in the treatment of hyperammonemia due to ornithine transcarbamylase deficiency
    Chen Yin Chen
    Division of Nephrology, Department of Medicine, Tian Sheng Memorial Hospital, Tong Kang, Ping Tong, Taiwan
    Ren Fail 29:661-5. 2007
    ..Removal of amino acids (AA) during CAVHDF has not been thoroughly investigated. AA losses in patients with urea cycle defects due to ornithine transcarbamylase deficiency treated by CAVHDF were analyzed...
  37. ncbi Survival after treatment with phenylacetate and benzoate for urea-cycle disorders
    Gregory M Enns
    Department of Pediatrics, Division of Medical Genetics, Stanford University, School of Medicine, Lucile Packard Children s Hospital, Stanford, CA 94305 5208, USA
    N Engl J Med 356:2282-92. 2007
    ..The combination of intravenous sodium phenylacetate and sodium benzoate has been shown to lower plasma ammonium levels and improve survival in small cohorts of patients with historically lethal urea-cycle enzyme defects...
  38. ncbi Estimation of the total number of disease-causing mutations in ornithine transcarbamylase (OTC) deficiency. Value of the OTC structure in predicting a mutation pathogenic potential
    J A Arranz
    Unitat de Metabolopaties, Hospital Materno Infantil Vall d Hebron, Barcelona, Spain
    J Inherit Metab Dis 30:217-26. 2007
    ..The previously reported mSNCs p.Arg26Gln, p.Arg40His, p.Glu52Lys, pLys88Asn, p.Arg129His, p.Asn161Ser, p.Thr178Met, p.His202Tyr, p.Ala208Thr and p.His302Arg, found in our cohort, are also discussed...
  39. ncbi [Hyperammonemia type II as an example of urea cycle disorder]
    Anna M Hawrot-Kawecka
    Z Kliniki Chorób Wewnqtrznych i Metabolicznych Slaskiej Akademii Medycznej, Katowicach
    Wiad Lek 59:512-5. 2006
    ..This article is the recapitulation of published studies and their implication on everyday clinical practice...
  40. ncbi Effects of arginine treatment on nutrition, growth and urea cycle function in seven Japanese boys with late-onset ornithine transcarbamylase deficiency
    Hironori Nagasaka
    Division of Metabolism, Chiba Children s Hospital, Chiba 266 0007, Japan
    Eur J Pediatr 165:618-24. 2006
    ..In addition to height and body weight, blood levels of proteins, lipids, growth hormone (GH), insulin-like growth factor-I (IGF-I) and IGF-binding protein -3 (IGFBP-3) were monitored...
  41. ncbi Ornithine transcarbamylase deficiencies in human males. Kinetic and immunochemical classification
    P Briand
    Biochim Biophys Acta 704:100-6. 1982
    ..Two of them were similar on the basis of their enzymatic properties and cross-reactive material amounts to two mouse ornithine transcarbamylase mutations:sparse-fur (spf) and sparse-fur with abnormal skin and hair (spf-ash)...
  42. ncbi Complete deletion of ornithine transcarbamylase gene confirmed by CGH array of X chromosome
    J A Arranz
    Unitat de Metabolopaties, Hospital Universitari Materno Infantil Vall d Hebron, Passeig de la Vall d Hebron, 119 129, 08035, Barcelona, Spain
    J Inherit Metab Dis 30:813. 2007
    ..The application of high-resolution genetic techniques allows the characterization of causative mutations such as large deletions in order to guide genetic counselling and prenatal diagnosis...
  43. ncbi Living donor liver transplantation for noncirrhotic inheritable metabolic liver diseases: impact of the use of heterozygous donors
    Daisuke Morioka
    Organ Transplant Unit, Kyoto University Hospital, Japan
    Transplantation 80:623-8. 2005
    ..The aim of the present study was to evaluate the outcome of LDLT for noncirrhotic inheritable metabolic liver disease (NCIMLD) to clarify the effects of using a heterozygous carrier as a donor...
  44. ncbi Analysis of mRNA transcripts improves the success rate of molecular genetic testing in OTC deficiency
    Katharina Engel
    Universitatsklinikum Munster, Klinik und Poliklinik für Kinder und Jugendmedizin, Albert Schweitzer Strasse 33, 48149 Munster, Germany
    Mol Genet Metab 94:292-7. 2008
    ..However, in about 20% of the patients with enzymatically confirmed OTC deficiency no mutation can be detected when sequencing of genomic DNA analyzing exons and adjacent intronic segments of the OTC gene is performed...
  45. ncbi Hypocitrullinemia in expanded newborn screening by LC-MS/MS is not a reliable marker for ornithine transcarbamylase deficiency
    C Cavicchi
    Metabolic and Muscular Unit, Clinic of Pediatric Neurology, AOU Meyer, Florence, Italy
    J Pharm Biomed Anal 49:1292-5. 2009
    ....
  46. ncbi Ammonia toxicity and its prevention in inherited defects of the urea cycle
    V Walker
    Department of Clinical Biochemistry, Southampton University Hospitals NHS Trust, Southampton General Hospital, Southampton, UK valerie walker suht swest nhs uk
    Diabetes Obes Metab 11:823-35. 2009
    ..Long-term correction is achieved by liver transplantation. Gene therapy for OTC deficiency is effective in animals, and work is ongoing to improve persistence and safety...
  47. ncbi Favorable effect of 4-phenylacetate on liver functions attributable to enhanced bile salt export pump expression in ornithine transcarbamylase-deficient children
    Hironori Nagasaka
    Division of Metabolism, Chiba Children s Hospital, Midori ku, Chiba, Japan
    Mol Genet Metab 100:123-8. 2010
    ..These results suggest that 4-PA enhanced liver BSEP/ABCB11 function and thereby improved liver functions in OTC-deficient children. For treatment of liver disorders requiring enhancement of BSEP function, 4-PA might be a candidate...
  48. ncbi An exon 1 deletion in OTC identified using chromosomal microarray analysis in a mother and her two affected deceased newborns: implications for the prenatal diagnosis of ornithine transcarbamylase deficiency
    Fabiola Quintero-Rivera
    Department of Pathology and Laboratory Medicine, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA
    Mol Genet Metab 101:413-6. 2010
    ....
  49. ncbi Late-onset ornithine transcarbamylase deficiency in male patients: prognostic factors and characteristics of plasma amino acid profile
    Eimei Harada
    Department of Pediatrics and Child Health, Kurume University School of Medicine, Asahi machi, Kurume, Japan
    Pediatr Int 48:105-11. 2006
    ..The aim of this study was to determine the prognostic factors that affect the prognosis of life, to explore a basis for therapeutic strategy...
  50. ncbi Rapid determination of orotic acid in urine by liquid chromatography-electrospray tandem mass spectrometry
    Mohamed S Rashed
    Department of Genetics, King Faisal Specialist Hospital and Research Centre, Riyadh 11211, Saudi Arabia
    Clin Chem 49:499-501. 2003
  51. ncbi [Analysis of clinical features, metabolic profiling and gene mutations of patients with ornithine transcarbamylase deficiency]
    Yan Wang
    Center of Clinical Genetics, Affiliated Bayi Children s Hospital, General Hospital of Beijing Military Command, Beijing 100700, P R China
    Zhonghua Yi Xue Yi Chuan Xue Za Zhi 31:148-51. 2014
    ....
  52. ncbi Gene symbol: OTC. Disease: ornithine carbamoyltransferase deficiency
    Wuh Liang Hwu
    Department of Pediatrics and Medical Genetics, National Taiwan University Hospital, Taipei
    Hum Genet 113:367. 2003
  53. ncbi Metabolic and neuropsychological phenotype in women heterozygous for ornithine transcarbamylase deficiency
    Kunsang Gyato
    North Shore Long Island Jewish Health System, Schneider Children s Hospital, Division of Child and Adolescent Psychiatry, New Hyde Park, NY, USA
    Ann Neurol 55:80-6. 2004
    ..The findings support the importance of maintaining meticulous metabolic control in children with urea cycle disorders, because even mildly symptomatic subjects demonstrate cognitive deficits...
  54. ncbi Genetic variation in the urea cycle: a model resource for investigating key candidate genes for common diseases
    Sabrina Mitchell
    Center for Human Genetics Research, Vanderbilt University Medical Center, Nashville, Tennessee 37232, USA
    Hum Mutat 30:56-60. 2009
    ..Screening all the genes in the pathway provides a catalog of variants that can be used in investigating candidate diseases...
  55. ncbi Cerebral atrophy after hyperammonaemic coma in a 23-year-old woman with OTC deficiency
    Francois Maillot
    Service de Medecine interne et nutrition, CHU Bretonneau, 2boulevard Tonnelle, 37044, Tours Cedex 9, France
    J Inherit Metab Dis 29:595-6. 2006
  56. ncbi Genetic approach to prenatal diagnosis in urea cycle defects
    Johannes Haberle
    Universitatsklinikum Munster, Klinik und Poliklinik für Kinderheilkunde, Munster, Germany
    Prenat Diagn 24:378-83. 2004
    ..To demonstrate the feasibility of prenatal diagnosis by molecular genetics in all urea cycle defects in order to improve and standardize the current approaches...
  57. ncbi Analysis of pyrimidine synthesis de novo intermediates in urine during crisis of a patient with ornithine transcarbamylase deficiency
    A B P van Kuilenburg
    Academic Medical Center, University of Amsterdam, Emma Children s Hospital, Laboratory Genetic Metabolic Diseases, Amsterdam, The Netherlands
    Nucleosides Nucleotides Nucleic Acids 25:1251-5. 2006
    ..The level of pyrimidine excretion appeared to be independent of the ammonia levels in blood, which were only mildly increased...
  58. pmc Vector sequences are not detected in tumor tissue from research subjects with ornithine transcarbamylase deficiency who previously received adenovirus gene transfer
    Li Zhong
    Gene Therapy Center, University of Massachusetts Medical School, Worcester, MA 01605, USA
    Hum Gene Ther 24:814-9. 2013
    ..Our results are informative in ruling out the possibility that the adenoviral vector might have contributed to the development of cancer in those two subjects...
  59. ncbi Fatal hyperammonemia resulting from a C-to-T mutation at a MspI site of the ornithine transcarbamylase gene
    D Hentzen
    Unite de Recherches sur les Handicaps Genetiques de l Enfant, INSERM U 12, Hopital des Enfants Malades, Paris, France
    Hum Genet 88:153-6. 1991
    ..8-kb abnormal fragment should be investigated on Southern blots of affected individuals...
  60. ncbi Four newly identified ornithine transcarbamylase (OTC) mutations (D126G, R129H, I172M and W332X) in Japanese male patients with early-onset OTC deficiency
    T Matsuura
    Department of Pediatrics, Kumamoto University School of Medicine, Japan
    Hum Mutat 3:402-6. 1994
  61. ncbi Seven new mutations in the human ornithine transcarbamylase gene
    M Tuchman
    Department of Pediatrics, University of Minnesota Medical School, Minneapolis 55455
    Hum Mutat 4:57-60. 1994
  62. ncbi Liver transplantation in urea cycle disorders
    J M Saudubray
    Department of Paediatrics, Hopital Necker Enfants Malades, 149 rue de Sevres, 75743 Paris, France
    Eur J Pediatr 158:S55-9. 1999
    ..Interestingly, three of these seven were liver-transplanted before the constitution of irreversible neurological damage. These three girls and their family declare their well-being, their feeling to be cured and enjoy their normal life...
  63. ncbi Lymphocyte mRNA analysis of the ornithine transcarbamylase gene in Italian OTCD male patients and manifesting carriers: identification of novel mutations
    M Giorgi
    Department of Pediatrics, University of Florence, Florence 50132, Italy
    Hum Mutat 15:380-1. 2000
    ..Here we show that PBL OTC mRNA analysis is useful to detect genetic lesions in male and female OTCD patients...
  64. ncbi Ornithine transcarbamylase deficiency in spf and spf-ash mice: genes, mRNAs and mRNA precursors
    A Ohtake
    Biochem Biophys Res Commun 146:1064-70. 1987
    ..These results suggest that ornithine transcarbamylase deficiency in the spf-ash results from a mutation, which to some extent affects mRNA processing...
  65. ncbi [Variants of inborn errors of metabolism with late onset but nevertheless life threatening course]
    E Plöchl
    Klinische Genetik, St Johanns Spital, Landeskliniken Salzburg, Germany
    Klin Padiatr 213:261-5. 2001
    ..There is a growing number of inborn errors of metabolism (IEM) with late onset but nevertheless life threatening course...
  66. pmc Identification of RNA splicing errors resulting in human ornithine transcarbamylase deficiency
    R P Carstens
    Department of Human Genetics, Yale University School of Medicine, New Haven, CT 06510
    Am J Hum Genet 48:1105-14. 1991
    ..We speculate that abnormal mRNA splicing may represent a relatively common mechanism in the pathogenesis of this disease...
  67. pmc Improved molecular diagnostics for ornithine transcarbamylase deficiency
    M Grompe
    Institute for Molecular Genetics, Baylor College of Medicine, Houston 77030
    Am J Hum Genet 48:212-22. 1991
    ..Utilization of the appropriate combination of these molecular techniques permitted accurate diagnostic evaluations in 17 of 18 families...
  68. ncbi Importance of ornithine transcarbamylase (OTC) deficiency in small intestine for urinary orotic acid excretion: analysis of OTC-deficient spf-ash mice with OTC transgene
    T Saheki
    Department of Biochemistry, Faculty of Medicine, Kagoshima University, Japan
    Biochim Biophys Acta 1270:87-93. 1995
    ..These results suggest that the level of OTC activity in the small intestine is important for production of orotic acid...
  69. ncbi Breeding experiments to combine the X-linked sparse-fur (spf) mutation with the autosomal recessive BALB/cByJ strain: testing the biochemical phenotype of double-mutant mice as a model for ammonia: fatty acyl CoA synergism
    I A Qureshi
    Service of Medical Genetics, Hopital Sainte Justine, Montreal, Quebec, Canada
    Biochem Biophys Res Commun 191:744-9. 1993
    ..It is postulated that the spf/Y (scad/scad) double-mutant may serve as a useful animal model to study the ammonia: fatty acyl CoA synergism...
  70. ncbi [The dibasic amino acid metabolic disorders]
    H Shimizu
    Department of Pediatrics, Jikei University School of Medicine
    Nihon Rinsho 50:1555-60. 1992
    ..We mainly described the recent knowledge for these disease and introduced the great advancement of the molecular biology in this field which makes us to give an early diagnosis for these disease to have an early treatment...
  71. ncbi Identification of 'private' mutations in patients with ornithine transcarbamylase deficiency
    M Tuchman
    Department of Pediatrics, Medical School University of Minnesota Hospitals, Minneapolis 55455, USA
    J Inherit Metab Dis 20:525-7. 1997
    ..As part of a continuing study of ornithine transcarbamylase deficiency, we now report an additional thirty novel mutations in the ornithine transcarbamylase gene, together with a brief summary of their clinical presentations...
  72. ncbi Characteristics of NO cycle coupling with urea cycle in non-hyperammonemic carriers of ornithine transcarbamylase deficiency
    Hironori Nagasaka
    Department of Pediatrics, Takarazuka City Hospital, 4 5 1 Kohama Cho, Takarazuka 665 0827, Japan
    Mol Genet Metab 109:251-4. 2013
    ..In two of those three, the occurrence of headaches was decreased. These results suggest that NO cycle coupling with the urea cycle is altered substantially even in non-hyperammonemic OTCD carriers, predisposing them to headaches...
  73. pmc 1H MRS allows brain phenotype differentiation in sisters with late onset ornithine transcarbamylase deficiency (OTCD) and discordant clinical presentations
    Andrea L Gropman
    Department of Neurology, Children s National Medical Center, 111 Michigan Avenue, NW, Washington, DC 20010, USA
    Mol Genet Metab 94:52-60. 2008
    ..The concentration of mI seen on (1)H MRS in PWM and FWM in this family could be used to deduce clinical symptomatology and may serve as a non-invasive marker of brain liability in OTCD...
  74. ncbi Acute extrapyramidal syndrome in mild ornithine transcarbamylase deficiency: metabolic stroke involving the caudate and putamen without metabolic decompensation
    C E Keegan
    Department of Pediatrics and Communicable Diseases, Division of Pediatric Genetics, University of Michigan School of Medicine, 3570 MSRB II, P O Box 0688, Ann Arbor, MI 48109 0688, USA
    Eur J Pediatr 162:259-63. 2003
    ..This case is novel in that the neurological insult affected the neostriatum of the basal ganglia and the episode occurred in the absence of an apparent metabolic abnormality, unique observations in a patient with OTC deficiency...
  75. ncbi Ornithine transcarbamylase deficiency presenting as recurrent abdominal pain in childhood
    Aizeddin A Mhanni
    Department of Pediatrics and Child Health, University of Manitoba, Winnipeg, Manitoba, Canada
    Pediatr Emerg Care 27:850-3. 2011
    ..Unnecessary invasive investigations of recurrent abdominal pain in childhood can be avoided by considering inborn errors of metabolism earlier in the differential diagnosis...
  76. ncbi Eight years after Jesse 's death, are human research subjects any safer?
    Paul Gelsinger
    Hastings Cent Rep 38:25-7. 2008
  77. ncbi Ornithine transcarbamylase deficiency: characterization of gene mutations and polymorphisms
    E O Oppliger Leibundgut
    Department of Clinical Chemistry, Inselspital, Berne, Switzerland
    Hum Mutat 8:333-9. 1996
    ..The K46R polymorphism in exon 2 and the Q27OR polymorphism in exon 8 were found in 36% and 4% of screened alleles, respectively. Two questionable polymorphisms in exon 4, F101L and L111P, were not present in any of the screened alleles...
  78. pmc Significant hepatic involvement in patients with ornithine transcarbamylase deficiency
    Renata C Gallagher
    Section of Clinical Genetics and Metabolism, Department of Pediatrics, University of Colorado School of Medicine and Children s Hospital Colorado, Aurora, CO Electronic address
    J Pediatr 164:720-725.e6. 2014
    ..To determine the frequency of significant liver injury and acute liver failure (ALF) in patients with ornithine transcarbamylase deficiency (OTCD), the most common urea cycle defect...
  79. ncbi [Molecular diagnosis of OTC gene mutation in a Chinese family with ornithine transcarbamylase deficiency]
    Lu lu Meng
    The Fourth Clinical Medicine College of Nanjing Medical University, Jiangsu 210029, P R China
    Zhonghua Yi Xue Yi Chuan Xue Za Zhi 30:195-8. 2013
    ..To detect potential mutations of OTC gene in a male infant affected with ornithine transcarbamylase deficiency...
  80. pmc Preclinical evaluation of a clinical candidate AAV8 vector for ornithine transcarbamylase (OTC) deficiency reveals functional enzyme from each persisting vector genome
    Lili Wang
    Gene Therapy Program, Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA
    Mol Genet Metab 105:203-11. 2012
    ..We suggest that the clinical candidate vector we have developed has the potential to achieve therapeutic effects in OTCD patients...
  81. ncbi Urea cycle disorders in Thai infants: a report of 5 cases
    Pornswan Wasant
    Department of Pediatrics, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand
    J Med Assoc Thai 85:S720-31. 2002
    ..Significant elevations of citrulline and L-glutamine were demonstrated. She was discharged in excellent condition to her home in Dubai, the United Arab Emirates...
  82. ncbi A novel arginine (245) to glutamine change in exon 8 of the ornithine carbamoyl transferase gene in two unrelated children presenting with late onset deficiency and showing the same enzymatic pattern
    B Gilbert-Dussardier
    Unite de Recherches sur les Handicaps Genetiques de l Enfant, INSERM U 393 Hôpital des Enfants Malades, Paris, France
    Hum Mol Genet 3:831-2. 1994
  83. ncbi A 3-base pair in-frame deletion in exon 8 (delGlu272/273) of the ornithine transcarbamylase gene in late-onset hyperammonemic coma
    B Segues
    Unité de Recherches sur les Handicaps Génétiques de l Enfant INSERM U 393, Departement de Pediatrie, Hopital des Enfants Malades, Paris
    Hum Mutat 8:373-4. 1996
  84. ncbi Recurrent pancreatitis in ornithine transcarbamylase deficiency
    Carlos E Prada
    Division of Human Genetics, Cincinnati Children s Hospital Medical Center, University of Cincinnati College of Medicine, Cincinnati, USA
    Mol Genet Metab 106:482-4. 2012
    ..The pathogenesis of acute pancreatitis in this patient population requires further elucidation. Pancreatitis significantly affected dietary/metabolic management and increased frequency of hospitalizations...
  85. ncbi [Analysis of clinical features, biochemical analysis and gene mutations in one Chinese pedigree with neonatal-onset ornithine transcarbamylase deficiency]
    Wei hua Sun
    Pediatrics Institute, Children s Hospital of Fudan University, Shanghai 201102, China
    Zhonghua Er Ke Za Zhi 49:356-60. 2011
    ....
  86. ncbi In vitro demonstration of intra-locus compensation using the ornithine transcarbamylase protein as model
    Gianpaolo Suriano
    Institute of Molecular Pathology and Immunology, University of Porto, Portugal
    Hum Mol Genet 16:2209-14. 2007
    ..We concluded that the presence of a threonine at position 135 in chimps rescues the deleterious effect of the methionine at position 125, in a mechanism of intra-locus compensation...
  87. pmc Induction and prevention of severe hyperammonemia in the spfash mouse model of ornithine transcarbamylase deficiency using shRNA and rAAV-mediated gene delivery
    Sharon C Cunningham
    Gene Therapy Research Unit, Children s Medical Research Institute and The Children s Hospital at Westmead, Wentworthville, New South Wales, Australia
    Mol Ther 19:854-9. 2011
    ..This result is favorable for clinical translation as it indicates that the threshold for therapeutic benefit is likely to be lower than indicated by earlier studies...
  88. pmc Phenylbutyrate improves nitrogen disposal via an alternative pathway without eliciting an increase in protein breakdown and catabolism in control and ornithine transcarbamylase-deficient patients
    Juan C Marini
    US Department of Agriculture Agricultural Research Service Children s Nutrition Research Center, Departments of Pediatrics and Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, USA
    Am J Clin Nutr 93:1248-54. 2011
    ....
  89. ncbi [Molecular basis of urea cycle disorders]
    I Matsuda
    Department of Pediatrics, Kumamoto University School of Medicine
    Nihon Rinsho 51:520-4. 1993
    ..Alleles are extremely heterogeneous in all enzyme deficiencies, in sharp difference from other inborn errors of metabolism, such as cystic fibrosis and hemoglobinopathies...
  90. ncbi An OTC deficiency 'phenocopy' in association with Klinefelter syndrome
    L Swarts
    Division of Chemical Pathology, University of Cape Town and NHLS, Cape Town, South Africa
    J Inherit Metab Dis 30:101. 2007
    ..We report on the novel association of OTC deficiency and Klinefelter syndrome with the additional interest of a probable unusual genetic defect underlying the OTC abnormality...
  91. pmc The molecular basis of ornithine transcarbamylase deficiency: modelling the human enzyme and the effects of mutations
    M Tuchman
    Department of Pediatrics, Medical School, University of Minnesota, Minneapolis 55455, USA
    J Med Genet 32:680-8. 1995
    ..The predicted effects of all known missense mutations and in frame deletions in the ornithine transcarbamylase gene on the structure and function of the mature enzyme are described...
  92. pmc Phenotypic variability in male patients carrying the mutant ornithine transcarbamylase (OTC) allele, Arg40His, ranging from a child with an unfavourable prognosis to an asymptomatic older adult
    I Matsuda
    Department of Paediatrics, School of Medicine, Kumamoto University, Japan
    J Med Genet 33:645-8. 1996
    ..We consider that the amount of protein ingested by these subjects may be one predisposing factor leading to the manifestation of this disease...
  93. pmc In vivo nitrogen metabolism in ornithine transcarbamylase deficiency
    M Yudkoff
    Division of Child Development, Children s Hospital of Philadelphia, Pennsylvania 19104, USA
    J Clin Invest 98:2167-73. 1996
    ..g., liver transplantation and gene therapy...
  94. ncbi Considerations in the difficult-to-manage urea cycle disorder patient
    Brendan Lee
    Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, USA
    Crit Care Clin 21:S19-25. 2005
    ....
  95. ncbi Ornithine transcarbamylase deficiency presenting as hepatitis
    Paul L Aronson
    Division of Emergency Medicine, The Children s Hospital of Philadelphia, Philadelphia, PA 19104, USA
    Pediatr Emerg Care 27:527-9. 2011
    ..Recognition of late presentations of this disease is important for survival and neurological outcome...
  96. ncbi Ornithine restores ureagenesis capacity and mitigates hyperammonemia in Otc(spf-ash) mice
    Juan C Marini
    Molecular and Human Genetics and Howard Hughes Medical Institute, Baylor College of Medicine, Houston, TX 77030, USA
    J Nutr 136:1834-8. 2006
    ..These data strongly suggest that ornithine has the potential for the biochemical correction of OTCD in Otc(spf-ash) mice...
  97. ncbi Public trust and research a decade later: what have we learned since Jesse Gelsinger's death?
    Mark Yarborough
    Center for Bioethics and Humanities, University of Colorado Denver, Mail Stop B 137, 13120 E 19th Avenue, Aurora, CO 80045, USA
    Mol Genet Metab 97:4-5. 2009
    ..Gelsinger's death and the authors note the need for greater emphasis on building public trust than has occurred to date in the broader biomedical research community...
  98. ncbi First example of hepatocyte transplantation to alleviate ornithine transcarbamylase deficiency, monitored by NMR-based metabonomics
    Cristina Legido-Quigley
    Department of Biomolecular Medicine, Faculty of Medicine, Sir Alexander Fleming Building, Imperial College, London, UK
    Bioanalysis 1:1527-35. 2009
    ....
  99. pmc Contrasting features of urea cycle disorders in human patients and knockout mouse models
    Joshua L Deignan
    Department of Pathology and Laboratory Medicine, David Geffen School of Medicine, University of California Los Angeles, CA 90095 1732, USA
    Mol Genet Metab 93:7-14. 2008
    ..Consequently, all of the current mouse models are highly useful for future research into novel pharmacological and dietary treatments and gene therapy protocols for the management of urea cycle disorders...
  100. ncbi [Ornithine transcarbamylase deficiency in adolescence and adulthood: first manifestation with life-threatening decompensation]
    M Burle
    Klinik fur Anasthesiologie, Intensivmedizin, Schmerztherapie und Notfallmedizin, Klinikum Ludwigsburg, Posilipostr 4, 71640, Ludwigsburg, Deutschland
    Anaesthesist 58:594-601. 2009
    ..Measurement of plasma ammonia levels is a simple yet important screening test for patients with unexpected stupor or delirium...
  101. pmc Diagnosis, symptoms, frequency and mortality of 260 patients with urea cycle disorders from a 21-year, multicentre study of acute hyperammonaemic episodes
    Marshall L Summar
    Vanderbilt University Medical Center, Nashville, TN, USA
    Acta Paediatr 97:1420-5. 2008
    ..A large longitudinal interventional study of patients with a urea cycle disorder (UCD) in hyperammonaemic crisis was undertaken to amass a significant body of data on their presenting symptoms and survival...

Research Grants16

  1. Satellite Symposium to the ASGT Annual Meeting
    James Wilson; Fiscal Year: 2006
    ..This application to[unreadable] the National Institute of Diabetes and Digestive and Kidney Diseases is for support of the[unreadable] AAV and Lentivirus Vectors: Integration and Insertional Mutagenesis Symposia. ..
  2. The molecular bases of inherited urea cycle disorders and ureagenesis regulation
    Mendel Tuchman; Fiscal Year: 2010
    ....
  3. COMMON POLYMORPHISM EFFECTS ON UREA CYCLE FUNCTION
    Marshall Summar; Fiscal Year: 2001
    ..Positive results in this study will lead to further study of other conditions involving the derangement of waste nitrogen disposal. ..
  4. Newborn screening for PKU and BH4 responsiveness
    Steven Dobrowolski; Fiscal Year: 2008
    ..High resolution melt profiling will play a role to identify BH4 responsive PKU patients. ..
  5. FilmArray-A Closed System for Multi-Pathogen Screening
    Steven Dobrowolski; Fiscal Year: 2005
    ..Pouches are designed to assay for candidate infectious agents consistent with clinical presentation. ..
  6. GENETIC & ENVIRONMENTAL DETERMINANTS OF CRANIOFACIAL DIS
    Brendan Lee; Fiscal Year: 2005
    ..Together, these studies will identify genes important in pathogenesis of human malformation and elucidate their modes of action in both cell autonomous and cell non-autonomous models mechanisms of development. ..
  7. Dysregulation of 3-prolyl-hydroxylation in Human Skeletal Dysplasias
    BRENDAN HL LEE; Fiscal Year: 2010
    ..e., the in vivo phenotypic and biochemical consequences of dysregulation of the 3-prolyl-hydroxylation machinery. ..
  8. Transcriptional Regulation of Craniofacial Skeletogenesis
    Brendan Lee; Fiscal Year: 2009
    ....
  9. TRANSCRIPTIONAL REGULATORS IN CHONDROGENESIS
    Brendan Lee; Fiscal Year: 2002
    ....
  10. The Role of Mitochondrial DNA Alterations in Cancer
    Lee Jun Wong; Fiscal Year: 2008
    ..Results from this research project will help us understand the functional role of mitochondrial DNA alterations in cancer and identify potential novel targets for more effective therapeutic development. ..
  11. In vivo function and tolerance to Factor VIII variants
    BRENDAN HL LEE; Fiscal Year: 2011
    ..abstract_text> ..
  12. Genotype Analysis for Diagnosis of Urea Cycle Disorders
    Steven Dobrowolski; Fiscal Year: 2007
    ..The proposed assay panels provide a means to readily assess gene that are well established to contribute to hyperammonemia. [unreadable] [unreadable] [unreadable]..
  13. ENTERAL PRECURSORS FOR UREA SYNTHESIS IN HUMANS
    Brendan Lee; Fiscal Year: 2006
    ..In addition it is anticipated that the results will benef it other individuals who have compromised protein metabolism. ..
  14. Analysis of ATP7B in Screening for Wilson Disease
    Steven Dobrowolski; Fiscal Year: 2004
    ..Prospective screening for WD improves efficacy of treatment and quality of life for affected patients. Genotyping is the best option to confirm results based upon ceruloplasmin analysis in asymptomatic patients. ..
  15. Adenoviral hepatocyte gene therapy in Citrullinemia
    Brendan Lee; Fiscal Year: 2005
    ..The data from these studies would be widely applicable to gene replacement therapy in a host of intrinsic disorders of liver metabolism as well as deficiencies of secretory proteins. ..