Liver Involvement in POLG Disease—a Multicentre Cohort Study of 202 Patients
Year: 2025
Type: article
Study design: Observational Study
Abstract: Liver involvement in POLG disease is common and associated with high morbidity and mortality. Detailed, large-scale, systematic studies of liver involvement are lacking. This study aims to describe the onset, clinical course and prognostic implications of liver involvement in POLG disease. We conducted a multinational, retrospective study including clinical, genetic and biochemical data from patients with confirmed POLG disease. Patients were stratified according to age of disease onset: early-onset (< 12 years), juvenile/adult-onset (12-40 years), and late-onset (> 40 years). Of the 202 patients, 110 (54%) had liver involvement. This could present at any time during the lifespan, but occurred more frequently in patients with early-onset disease (76/98, 78%). Median onset age for liver involvement in females was 7 years (range: 1 month to 50 years), and 21 months in males (birth to 71 years). Infection-triggered disease onset carried a significantly higher risk of liver involvement than spontaneous or other disease triggers. Eighty-five percent of those with liver involvement also had epilepsy. Liver involvement was an indicator of poor prognosis and was significantly associated with worse survival. This study provides a comprehensive description of liver involvement in a large cohort of POLG disease patients. Liver involvement is common in this disease and associated with significantly worse survival. POLG disease should be considered in children presenting with liver involvement, and rapid genetic testing may guide management decisions. Our findings emphasize the need for early vigilance in monitoring liver involvement in all patients with confirmed POLG disease, particularly those with early-onset disease and during intercurrent infection.
DOI: 10.1002/jimd.70112
Authors: Erle Kristensen, Karin Naess, Martin Engvall, Claus Klingenberg, Magnhild Rasmussen, Eylert Brodtkorb, Elsebet Ostergaard, Irenaeus de Coo, Leticia Pias‐Peleteiro, Pirjo Isohanni, Johanna Uusimaa, Kari Majamaa, Mikko Kärppä, Mika H. Martikainen, Juan Dario Ortigoza‐Escobar, Trine Tangeraas, Siren Berland, Carolyn M. Sue, Judith Sylvia Walker, Emma Harrison, Heather Biggs, Rita Horvath, Niklas Darin, Shamima Rahman, Omar Hikmat
Institutions: Oslo University Hospital, University of Bergen, Karolinska University Hospital, Karolinska Institutet, University Hospital of North Norway, UiT The Arctic University of Norway, Norwegian University of Science and Technology, St Olav's University Hospital, University of Copenhagen, Copenhagen University Hospital, Rigshospitalet, Maastricht University, Hospital Sant Joan de Déu Barcelona, University of Helsinki, Helsinki University Hospital, Helsinki Children's Hospital, Oulu University Hospital, University of Oulu, University of Turku, Turku University Hospital, Institut de Recerca Sant Joan de Déu, Haukeland University Hospital, UNSW Sydney, Prince of Wales Hospital, South Eastern Sydney Local Health District, Neuroscience Research Australia, University of Cambridge, Sahlgrenska University Hospital, University of Gothenburg, Great Ormond Street Hospital for Children NHS Foundation Trust, University College London
Language: English
Subfield: Clinical Biochemistry
Domain: Life Sciences
Open Access status: green
Funders: Wellcome Trust, Muscular Dystrophy UK, Action for A-T, UK Research and Innovation, National Institute for Health and Care Research, Ataxia UK, Rosetrees Trust, Great Ormond Street Hospital Charity, Helse Vest, Lily Foundation, Medical Research Council, NIHR Cambridge Biomedical Research Centre, Oslo universitetssykehus HF
OpenAlex ID: W4416238615