PuSH - Publication Server of Helmholtz Zentrum München

Lenz, D.* ; Schlieben, L.D. ; Shimura, M. ; Bianzano, A.* ; Smirnov, D. ; Kopajtich, R. ; Berutti, R. ; Adam, R.* ; Aldrian, D.* ; Baric, I.* ; Baumann, U.* ; Bozbulut, N.E.* ; Brugger, M.* ; Brunet, T.* ; Bufler, P.* ; Burnyte, B.* ; Calvo, P.L.* ; Crushell, E.* ; Dalgıç, B.* ; Das, A.M.* ; Dezsőfi, A.* ; Distelmaier, F.* ; Fichtner, A.* ; Freisinger, P.* ; Garbade, S.F.* ; Gaspar, H.* ; Goujon, L.* ; Hadzic, N.* ; Hartleif, S.* ; Hegen, B.* ; Hempel, M.* ; Henning, S.* ; Hoerning, A.* ; Houwen, R.* ; Hughes, J.* ; Iorio, R.* ; Iwanicka-Pronicka, K.* ; Jankofsky, M.* ; Junge, N.* ; Kanavaki, I.* ; Kansu, A.* ; Kaspar, S.* ; Kathemann, S.* ; Kelly, D.* ; Kırsaçlıoğlu, C.T.* ; Knoppke, B.* ; Kohl, M.* ; Kölbel, H.* ; Kolker, S.* ; Konstantopoulou, V.* ; Krylova, T.* ; Kuloglu, Z.* ; Kuster, A.* ; Laass, M.W.* ; Lainka, E.* ; Lurz, E.* ; Mandel, H.* ; Mayerhanser, K.* ; Mayr, J.A.* ; McKiernan, P.* ; McLean, P.* ; McLin, V.* ; Mention, K.* ; Müller, H.* ; Pasquier, L.* ; Pavlov, M. ; Pechatnikova, N.* ; Peters, B.* ; Petkovic Ramadža, D.* ; Piekutowska-Abramczuk, D.* ; Pilic, D.* ; Rajwal, S.* ; Rock, N.* ; Roetig, A.* ; Santer, R.* ; Schenk, W.* ; Semenova, N.* ; Sokollik, C.* ; Sturm, E.* ; Taylor, R.W.* ; Tschiedel, E.* ; Urbonas, V.* ; Urreizti, R.* ; Vermehren, J.* ; Vockley, J.* ; Vogel, G.F.* ; Wagner, M.* ; van der Woerd, W.* ; Wortmann, S.* ; Zakharova, E.* ; Hoffmann, G.F.* ; Meitinger, T.* ; Murayama, K.* ; Staufner, C.* ; Prokisch, H.

Genetic landscape of pediatric acute liver failure of indeterminate origin.

Hepatology 79, 1075-1087 (2023)
Publ. Version/Full Text DOI PMC
Open Access Gold (Paid Option)
BACKGROUND AIMS: Pediatric acute liver failure (PALF) is a life-threatening condition. In Europe, 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. METHODS: 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 (RALF). 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 (46%), and in children with RALF (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, 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 transplants. CONCLUSION: 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.
Altmetric
Additional Metrics?
[➜Log in]
Edit extra informations Login
Publication type Article: Journal article
Document type Scientific Article
Corresponding Author
ISSN (print) / ISBN 0270-9139
e-ISSN 1527-3350
Journal Hepatology
Quellenangaben Volume: 79, Issue: 5, Pages: 1075-1087 Article Number: , Supplement: ,
Publisher Wiley
Publishing Place Hoboken, NJ
Non-patent literature Publications
Reviewing status Peer reviewed
Institute(s) Institute of Neurogenomics (ING)