caa a22 4500 475787021 CHVBK 20180406123701.0 cr unu---uuuuu 170329e20001201xx s 000 0 eng 10.1007/PL00014402 doi (NATIONALLICENCE)springer-10.1007/PL00014402 The molecular basis of ornithine transcarbamylase deficiency [Elektronische Daten] [Mendel Tuchman, Beth A. McCullough, Marc Yudkoff] The ornithine transcarbamylase (OTC) gene is located on the short arm of the X-chromosome and encodes the second enzyme of the urea cycle. OTC deficiency is an X-linked disorder that causes hyperammonemia leading to brain damage, mental retardation and death. The clinical and biochemical phenotype is extremely variable and can only partially be explained by the genotype. We identified mutations in the OTC gene of more than 150 patients with OTC deficiency. The "neonatal onset” group of patients has mutations that abolish enzyme activity, whereas the "late onset group” shows partial enzyme deficiency to variable degree. Of the mutations, 60% are associated exclusively with acute neonatal hyperammonemic coma while the remaining cause "late onset” disease. Several symptomatic and asymptomatic adults have now been identified to have deleterious mutations in the OTC gene leading to predisposition to hyperammonemia. Conclusion The enlarging clinical, biochemical and molecular spectrum observed in patients with ornithine transcarbamylase deficiency suggests that this disorder behaves like a single gene disorder at one end of the spectrum and as a multi-factorial disease at the other. Springer-Verlag Berlin Heidelberg, 2000 Key words Germinal mutation nationallicence Hyperammonemia nationallicence Inborn error of metabolism nationallicence Ornithine transcarbamylase nationallicence Urea cycle nationallicence Tuchman Mendel Children's Research Institute, Children's National Medical Center, 111 Michigan Avenue NW, Washington DC 20010-2970, USA e-mail: mtuchman@cnmc.org Tel.: +1-202-8842549; Fax: +1-202-8846014, US aut McCullough Beth A. Departments of Molecular and Cellular Engineering, Medicine and Surgery, Institute for Human Gene Therapy and Wistar Institute, University of Pennsylvania, Philadelphia, USA, US aut Yudkoff Marc Department of Pediatrics, Children's Seashore house, Children's Hospital of Philadelphia University of Pennsylvania, Philadelphia, USA, US aut https://doi.org/10.1007/PL00014402 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/PL00014402 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Tuchman Mendel Children's Research Institute, Children's National Medical Center, 111 Michigan Avenue NW, Washington DC 20010-2970, USA e-mail: mtuchman@cnmc.org Tel.: +1-202-8842549; Fax: +1-202-8846014, US aut NATIONALLICENCE 700 1- McCullough Beth A. Departments of Molecular and Cellular Engineering, Medicine and Surgery, Institute for Human Gene Therapy and Wistar Institute, University of Pennsylvania, Philadelphia, USA, US aut NATIONALLICENCE 700 1- Yudkoff Marc Department of Pediatrics, Children's Seashore house, Children's Hospital of Philadelphia University of Pennsylvania, Philadelphia, USA, US aut Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer