Buchumschlag

Genetic landscape of pediatric acute liver failure of indeterminate origin

Background and Aims: - Pediatric acute liver failure (PALF) is a life-threatening condition. In Europe, the main causes are viral infections (12%-16%) and inherited metabolic diseases (14%-28%). Yet, in up to 50% of cases the underlying etiology remains elusive, challenging clinical management, in...

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Bibliographische Detailangaben
Hauptverfasser: Lenz, Dominic (VerfasserIn) , Schlieben, Lea D. (VerfasserIn) , Shimura, Masaru (VerfasserIn) , Bianzano, Alyssa (VerfasserIn) , Smirnov, Dmitrii (VerfasserIn) , Kopajtich, Robert (VerfasserIn) , Berutti, Riccardo (VerfasserIn) , Adam, Rüdiger (VerfasserIn) , Aldrian, Denise (VerfasserIn) , Baric, Ivo (VerfasserIn) , Baumann, Ulrich (VerfasserIn) , Bozbulut, Neslihan E. (VerfasserIn) , Brugger, Melanie (VerfasserIn) , Brunet, Theresa (VerfasserIn) , Bufler, Philip (VerfasserIn) , Burnytė, Birutė (VerfasserIn) , Calvo, Pier L. (VerfasserIn) , Crushell, Ellen (VerfasserIn) , Dalgiç, Buket (VerfasserIn) , Das, Anibh M. (VerfasserIn) , Dezsőfi, Antal (VerfasserIn) , Distelmaier, Felix (VerfasserIn) , Fichtner, Alexander (VerfasserIn) , Freisinger, Peter (VerfasserIn) , Garbade, Sven (VerfasserIn) , Gaspar, Harald (VerfasserIn) , Goujon, Louise (VerfasserIn) , Hadzic, Nedim (VerfasserIn) , Hartleif, Steffen (VerfasserIn) , Hegen, Bianca (VerfasserIn) , Hempel, Maja (VerfasserIn) , Henning, Stephan (VerfasserIn) , Hoerning, Andre (VerfasserIn) , Houwen, Roderick (VerfasserIn) , Hughes, Joanne (VerfasserIn) , Iorio, Raffaele (VerfasserIn) , Iwanicka-Pronicka, Katarzyna (VerfasserIn) , Jankofsky, Martin (VerfasserIn) , Junge, Norman (VerfasserIn) , Kanavaki, Ino (VerfasserIn) , Kansu, Aydan (VerfasserIn) , Kaspar, Sonja (VerfasserIn) , Kathemann, Simone (VerfasserIn) , Kelly, Deidre (VerfasserIn) , Kirsaçlioğlu, Ceyda T. (VerfasserIn) , Knoppke, Birgit (VerfasserIn) , Kohl, Martina (VerfasserIn) , Kölbel, Heike (VerfasserIn) , Kölker, Stefan (VerfasserIn) , Konstantopoulou, Vassiliki (VerfasserIn) , Krylova, Tatiana (VerfasserIn) , Kuloğlu, Zarife (VerfasserIn) , Kuster, Alice (VerfasserIn) , Laass, Martin W. (VerfasserIn) , Lainka, Elke (VerfasserIn) , Lurz, Eberhard (VerfasserIn) , Mandel, Hanna (VerfasserIn) , Mayerhanser, Katharina (VerfasserIn) , Mayr, Johannes A. (VerfasserIn) , McKiernan, Patrick (VerfasserIn) , McClean, Patricia (VerfasserIn) , McLin, Valerie (VerfasserIn) , Mention, Karine (VerfasserIn) , Müller, Hanna (VerfasserIn) , Pasquier, Laurent (VerfasserIn) , Pavlov, Martin (VerfasserIn) , Pechatnikova, Natalia (VerfasserIn) , Peters, Bianca (VerfasserIn) , Petković Ramadža, Danijela (VerfasserIn) , Piekutowska-Abramczuk, Dorota (VerfasserIn) , Pilic, Denisa (VerfasserIn) , Rajwal, Sanjay (VerfasserIn) , Rock, Nathalie (VerfasserIn) , Roetig, Agnès (VerfasserIn) , Santer, René (VerfasserIn) , Schenk, Wilfried (VerfasserIn) , Semenova, Natalia (VerfasserIn) , Sokollik, Christiane (VerfasserIn) , Sturm, Ekkehard (VerfasserIn) , Taylor, Robert W. (VerfasserIn) , Tschiedel, Eva (VerfasserIn) , Urbonas, Vaidotas (VerfasserIn) , Urreizti, Roser (VerfasserIn) , Vermehren, Jan (VerfasserIn) , Vockley, Jerry (VerfasserIn) , Vogel, Georg-Friedrich (VerfasserIn) , Wagner, Matias (VerfasserIn) , van der Woerd, Wendy (VerfasserIn) , Wortmann, Saskia B. (VerfasserIn) , Zakharova, Ekaterina (VerfasserIn) , Hoffmann, Georg F. (VerfasserIn) , Meitinger, Thomas (VerfasserIn) , Murayama, Kei (VerfasserIn) , Staufner, Christian (VerfasserIn) , Prokisch, Holger (VerfasserIn)
Dokumenttyp: Article (Journal)
Sprache:Englisch
Veröffentlicht: May 2024
In: Hepatology
Year: 2024, Jahrgang: 79, Heft: 5, Pages: 1075-1087
ISSN:1527-3350
DOI:10.1097/HEP.0000000000000684
Online-Zugang:Verlag, kostenfrei, Volltext: https://doi.org/10.1097/HEP.0000000000000684
Verlag, kostenfrei, Volltext: https://journals.lww.com/hep/fulltext/2024/05000/genetic_landscape_of_pediatric_acute_liver_failure.14.aspx
Volltext
Verfasserangaben:Dominic Lenz, Lea D. Schlieben, Masaru Shimura, Alyssa Bianzano, Dmitrii Smirnov, Robert Kopajtich, Riccardo Berutti, Rüdiger Adam, Denise Aldrian, Ivo Baric, Ulrich Baumann, Neslihan E. Bozbulut, Melanie Brugger, Theresa Brunet, Philip Bufler, Birutė Burnytė, Pier L. Calvo, Ellen Crushell, Buket Dalgiç, Anibh M. Das, Antal Dezsőfi, Felix Distelmaier, Alexander Fichtner, Peter Freisinger, Sven F. Garbade, Harald Gaspar, Louise Goujon, Nedim Hadzic, Steffen Hartleif, Bianca Hegen, Maja Hempel, Stephan Henning, Andre Hoerning, Roderick Houwen, Joanne Hughes, Raffaele Iorio, Katarzyna Iwanicka-Pronicka, Martin Jankofsky, Norman Junge, Ino Kanavaki, Aydan Kansu, Sonja Kaspar, Simone Kathemann, Deidre Kelly, Ceyda T. Kirsaçlioğlu, Birgit Knoppke, Martina Kohl, Heike Kölbel, Stefan Kölker, Vassiliki Konstantopoulou, Tatiana Krylova, Zarife Kuloğlu, Alice Kuster, Martin W. Laass, Elke Lainka, Eberhard Lurz, Hanna Mandel, Katharina Mayerhanser, Johannes A. Mayr, Patrick McKiernan, Patricia McClean, Valerie McLin, Karine Mention, Hanna Müller, Laurent Pasquier, Martin Pavlov, Natalia Pechatnikova, Bianca Peters, Danijela Petković Ramadža, Dorota Piekutowska-Abramczuk, Denisa Pilic, Sanjay Rajwal, Nathalie Rock, Agnès Roetig, René Santer, Wilfried Schenk, Natalia Semenova, Christiane Sokollik, Ekkehard Sturm, Robert W. Taylor, Eva Tschiedel, Vaidotas Urbonas, Roser Urreizti, Jan Vermehren, Jerry Vockley, Georg-Friedrich Vogel, Matias Wagner, Wendy van der Woerd, Saskia B. Wortmann, Ekaterina Zakharova, Georg F. Hoffmann, Thomas Meitinger, Kei Murayama, Christian Staufner, Holger Prokisch

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245 1 0 |a Genetic landscape of pediatric acute liver failure of indeterminate origin  |c Dominic Lenz, Lea D. Schlieben, Masaru Shimura, Alyssa Bianzano, Dmitrii Smirnov, Robert Kopajtich, Riccardo Berutti, Rüdiger Adam, Denise Aldrian, Ivo Baric, Ulrich Baumann, Neslihan E. Bozbulut, Melanie Brugger, Theresa Brunet, Philip Bufler, Birutė Burnytė, Pier L. Calvo, Ellen Crushell, Buket Dalgiç, Anibh M. Das, Antal Dezsőfi, Felix Distelmaier, Alexander Fichtner, Peter Freisinger, Sven F. Garbade, Harald Gaspar, Louise Goujon, Nedim Hadzic, Steffen Hartleif, Bianca Hegen, Maja Hempel, Stephan Henning, Andre Hoerning, Roderick Houwen, Joanne Hughes, Raffaele Iorio, Katarzyna Iwanicka-Pronicka, Martin Jankofsky, Norman Junge, Ino Kanavaki, Aydan Kansu, Sonja Kaspar, Simone Kathemann, Deidre Kelly, Ceyda T. Kirsaçlioğlu, Birgit Knoppke, Martina Kohl, Heike Kölbel, Stefan Kölker, Vassiliki Konstantopoulou, Tatiana Krylova, Zarife Kuloğlu, Alice Kuster, Martin W. Laass, Elke Lainka, Eberhard Lurz, Hanna Mandel, Katharina Mayerhanser, Johannes A. Mayr, Patrick McKiernan, Patricia McClean, Valerie McLin, Karine Mention, Hanna Müller, Laurent Pasquier, Martin Pavlov, Natalia Pechatnikova, Bianca Peters, Danijela Petković Ramadža, Dorota Piekutowska-Abramczuk, Denisa Pilic, Sanjay Rajwal, Nathalie Rock, Agnès Roetig, René Santer, Wilfried Schenk, Natalia Semenova, Christiane Sokollik, Ekkehard Sturm, Robert W. Taylor, Eva Tschiedel, Vaidotas Urbonas, Roser Urreizti, Jan Vermehren, Jerry Vockley, Georg-Friedrich Vogel, Matias Wagner, Wendy van der Woerd, Saskia B. Wortmann, Ekaterina Zakharova, Georg F. Hoffmann, Thomas Meitinger, Kei Murayama, Christian Staufner, Holger Prokisch 
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520 |a Background and Aims: - Pediatric acute liver failure (PALF) is a life-threatening condition. In Europe, the main causes are viral infections (12%-16%) and inherited metabolic diseases (14%-28%). Yet, in up to 50% of cases the underlying etiology remains elusive, challenging clinical management, including liver transplantation. We systematically studied indeterminate PALF cases referred for genetic evaluation by whole-exome sequencing (WES), and analyzed phenotypic and biochemical markers, and the diagnostic yield of WES in this condition. - Approach and Results: - With this international, multicenter observational study, patients (0-18 y) with indeterminate PALF were analyzed by WES. Data on the clinical and biochemical phenotype were retrieved and systematically analyzed. - Results: - In total, 260 indeterminate PALF patients from 19 countries were recruited between 2011 and 2022, of whom 59 had recurrent PALF. WES established a genetic diagnosis in 37% of cases (97/260). Diagnostic yield was highest in children with PALF in the first year of life (41%), and in children with recurrent acute liver failure (64%). Thirty-six distinct disease genes were identified. Defects in NBAS (n=20), MPV17 (n=8), and DGUOK (n=7) were the most frequent findings. When categorizing, the most frequent were mitochondrial diseases (45%), disorders of vesicular trafficking (28%), and cytosolic aminoacyl-tRNA synthetase deficiencies (10%). One-third of patients had a fatal outcome. Fifty-six patients received liver transplantation. - Conclusions: - This study elucidates a large contribution of genetic causes in PALF of indeterminate origin with an increasing spectrum of disease entities. The high proportion of diagnosed cases and potential treatment implications argue for exome or in future rapid genome sequencing in PALF diagnostics. 
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700 1 |a Das, Anibh M.  |e VerfasserIn  |4 aut 
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SER |a journal 
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Schlieben, Masaru Shimura, Alyssa Bianzano, Dmitrii Smirnov, Robert Kopajtich, Riccardo Berutti, Rüdiger Adam, Denise Aldrian, Ivo Baric, Ulrich Baumann, Neslihan E. Bozbulut, Melanie Brugger, Theresa Brunet, Philip Bufler, Birutė Burnytė, Pier L. Calvo, Ellen Crushell, Buket Dalgiç, Anibh M. Das, Antal Dezsőfi, Felix Distelmaier, Alexander Fichtner, Peter Freisinger, Sven F. Garbade, Harald Gaspar, Louise Goujon, Nedim Hadzic, Steffen Hartleif, Bianca Hegen, Maja Hempel, Stephan Henning, Andre Hoerning, Roderick Houwen, Joanne Hughes, Raffaele Iorio, Katarzyna Iwanicka-Pronicka, Martin Jankofsky, Norman Junge, Ino Kanavaki, Aydan Kansu, Sonja Kaspar, Simone Kathemann, Deidre Kelly, Ceyda T. Kirsaçlioğlu, Birgit Knoppke, Martina Kohl, Heike Kölbel, Stefan Kölker, Vassiliki Konstantopoulou, Tatiana Krylova, Zarife Kuloğlu, Alice Kuster, Martin W. Laass, Elke Lainka, Eberhard Lurz, Hanna Mandel, Katharina Mayerhanser, Johannes A. Mayr, Patrick McKiernan, Patricia McClean, Valerie McLin, Karine Mention, Hanna Müller, Laurent Pasquier, Martin Pavlov, Natalia Pechatnikova, Bianca Peters, Danijela Petković Ramadža, Dorota Piekutowska-Abramczuk, Denisa Pilic, Sanjay Rajwal, Nathalie Rock, Agnès Roetig, René Santer, Wilfried Schenk, Natalia Semenova, Christiane Sokollik, Ekkehard Sturm, Robert W. Taylor, Eva Tschiedel, Vaidotas Urbonas, Roser Urreizti, Jan Vermehren, Jerry Vockley, Georg-Friedrich Vogel, Matias Wagner, Wendy van der Woerd, Saskia B. Wortmann, Ekaterina Zakharova, Georg F. Hoffmann, Thomas Meitinger, Kei Murayama, Christian Staufner, Holger Prokisch"]},"language":["eng"],"note":["Gesehen am 07.08.2024"],"recId":"1898053626","person":[{"role":"aut","family":"Lenz","given":"Dominic","display":"Lenz, Dominic"},{"given":"Lea D.","display":"Schlieben, Lea D.","family":"Schlieben","role":"aut"},{"display":"Shimura, Masaru","given":"Masaru","role":"aut","family":"Shimura"},{"role":"aut","family":"Bianzano","given":"Alyssa","display":"Bianzano, Alyssa"},{"given":"Dmitrii","display":"Smirnov, Dmitrii","role":"aut","family":"Smirnov"},{"family":"Kopajtich","role":"aut","display":"Kopajtich, Robert","given":"Robert"},{"display":"Berutti, Riccardo","given":"Riccardo","family":"Berutti","role":"aut"},{"display":"Adam, Rüdiger","given":"Rüdiger","role":"aut","family":"Adam"},{"display":"Aldrian, Denise","given":"Denise","role":"aut","family":"Aldrian"},{"display":"Baric, Ivo","given":"Ivo","family":"Baric","role":"aut"},{"display":"Baumann, 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JSO |a René","display":"Santer, René","role":"aut","family":"Santer"},{"given":"Wilfried","display":"Schenk, Wilfried","family":"Schenk","role":"aut"},{"role":"aut","family":"Semenova","display":"Semenova, Natalia","given":"Natalia"},{"family":"Sokollik","role":"aut","display":"Sokollik, Christiane","given":"Christiane"},{"family":"Sturm","role":"aut","display":"Sturm, Ekkehard","given":"Ekkehard"},{"given":"Robert W.","display":"Taylor, Robert W.","family":"Taylor","role":"aut"},{"role":"aut","family":"Tschiedel","display":"Tschiedel, Eva","given":"Eva"},{"family":"Urbonas","role":"aut","given":"Vaidotas","display":"Urbonas, Vaidotas"},{"given":"Roser","display":"Urreizti, Roser","role":"aut","family":"Urreizti"},{"family":"Vermehren","role":"aut","display":"Vermehren, Jan","given":"Jan"},{"display":"Vockley, Jerry","given":"Jerry","family":"Vockley","role":"aut"},{"family":"Vogel","role":"aut","given":"Georg-Friedrich","display":"Vogel, Georg-Friedrich"},{"family":"Wagner","role":"aut","given":"Matias","display":"Wagner, Matias"},{"role":"aut","family":"van der Woerd","given":"Wendy","display":"van der Woerd, Wendy"},{"given":"Saskia B.","display":"Wortmann, Saskia B.","role":"aut","family":"Wortmann"},{"family":"Zakharova","role":"aut","display":"Zakharova, Ekaterina","given":"Ekaterina"},{"family":"Hoffmann","role":"aut","display":"Hoffmann, Georg F.","given":"Georg F."},{"role":"aut","family":"Meitinger","given":"Thomas","display":"Meitinger, Thomas"},{"display":"Murayama, Kei","given":"Kei","role":"aut","family":"Murayama"},{"display":"Staufner, Christian","given":"Christian","role":"aut","family":"Staufner"},{"given":"Holger","display":"Prokisch, Holger","role":"aut","family":"Prokisch"}]} 
SRT |a LENZDOMINIGENETICLAN2024 

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