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Vogel, G.F.* ; Mozer-Glassberg, Y.* ; Landau, Y.E.* ; Schlieben, L.D. ; Prokisch, H. ; Feichtinger, R.G.* ; Mayr, J.A.* ; Brennenstuhl, H.* ; Schröter, J.* ; Pechlaner, A.* ; Alkuraya, F.S.* ; Baker, J.J.* ; Barcia, G.* ; Baric, I.* ; Braverman, N.* ; Burnyte, B.* ; Christodoulou, J.* ; Ciara, E.* ; Coman, D.* ; Das, A.M.* ; Darin, N.* ; Della Marina, A.* ; Distelmaier, F.* ; Eklund, E.A.* ; Ersoy, M.* ; Fang, W.* ; Gaignard, P.* ; Ganetzky, R.D.* ; Gonzales, E.* ; Howard, C.R.* ; Hughes, J.* ; Konstantopoulou, V.* ; Kose, M.* ; Kerr, M.* ; Khan, A.* ; Lenz, D.* ; McFarland, R.* ; Margolis, M.G.* ; Morrison, K.* ; Müller, T.* ; Murayama, K.* ; Nicastro, E.* ; Pennisi, A.* ; Peters, H.* ; Piekutowska-Abramczuk, D.* ; Rötig, A.* ; Santer, R.* ; Scaglia, F.* ; Schiff, M.* ; Shagrani, M.* ; Sharrard, M.* ; Soler-Alfonso, C.* ; Staufner, C.* ; Storey, I.* ; Stormon, M.* ; Taylor, R.W.* ; Thorburn, D.R.* ; Teles, E.L.* ; Wang, J.S.* ; Weghuber, D.* ; Wortmann, S.*

Genotypic and phenotypic spectrum of infantile liver failure due to pathogenic TRMU variants.

Genet. Med. 25:100314 (2022)
Verlagsversion DOI PMC
Open Access Gold (Paid Option)
Creative Commons Lizenzvertrag
Purpose: The study aimed to define the genotypic and phenotypic spectrum of reversible acute liver failure (ALF) of infancy resulting from biallelic pathogenic TRMU variants and to determine the role of cysteine supplementation in its treatment. Methods: Individuals with biallelic (likely) pathogenic variants in TRMU were studied through an international retrospective collection of de-identified patient data. Results: In 62 individuals, including 30 previously unreported cases, we described 48 (likely) pathogenic TRMU variants, of which, 18 were novel. Of these 62 individuals, 42 were alive at a median age of 6.8 (0.6-22) years after a median follow up of 3.6 (0.1-22) years. The most frequent finding, occurring in all but 2 individuals, was liver involvement. ALF occurred only in the first year of life and was reported in 43 of 62 individuals, 11 of whom received liver transplantation. Loss-of-function TRMU variants were associated with poor survival. Supplementation with at least 1 cysteine source, typically N-acetylcysteine, improved survival significantly. Neurodevelopmental delay was observed in 11 individuals and persisted in 4 of the survivors, but we were unable to determine whether this was a primary or a secondary consequence of TRMU deficiency. Conclusion: In most patients, TRMU-associated ALF is a transient, reversible disease and cysteine supplementation improved survival.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Korrespondenzautor
Schlagwörter Acute Liver Failure ; Cysteine ; Liver Transplantation ; Mitochondrial Disease ; Treatment; Mitochondrial; Deficiency; Diagnosis; Disease
ISSN (print) / ISBN 1530-0366
e-ISSN 1098-3600
Zeitschrift Genetics in Medicine
Quellenangaben Band: 25, Heft: 6, Seiten: , Artikelnummer: 100314 Supplement: ,
Verlag Lippincott Williams & Wilkins
Verlagsort Baltimore, Md.
Nichtpatentliteratur Publikationen
Begutachtungsstatus Peer reviewed
Institut(e) Institute of Neurogenomics (ING)
Förderungen UK NIHR Biomedical Research Centre for Ageing and Age-related Disease award
Lily Foundation
Medical Research Council
Medical Research Council International Centre for Genomic Medicine in Neuromuscular Disease
Mitochondrial Disease Patient Cohort (United Kingdom)
Wellcome Trust Centre for Mitochondrial Research
Saol Therapeutics
Optimizing diagnostics and treatment for patients with mitochondrial diseases FWF
PTC Therapeutics
Courage for a Cure Foundation
Mervar Foundation
Frontiers of Congenital Disorders of Glycosylation Consortia (FCDGC)
North American Mitochondrial Disease Consortia
National Institutes of Health
European Reference Network for Hereditary Metabolic Disorders (MetabERN)
MitoCanada
Astellas Pharma Inc.
UK NHS Highly Specialised Service for Rare Mitochondrial Disorders of Adults and Children
King Salman Center for Disability Research
Bavarian State Ministry of Health and Care
BMBF (German Federal Ministry of Education and Research)
Victorian Government's Operational Infrastructure Support program
National Health and Medical Research Council (NHMRC)
New South Wales Office of Health and Medical Research Council Sydney Genomics Collaborative grant
Pathological Society