Liver Involvement in <scp>POLG</scp> Disease—a Multicentre Cohort Study of 202 Patients

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.

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Publication Details

Journal
Journal of Inherited Metabolic Disease
Published
2025-11-01
DOI
https://doi.org/10.1002/jimd.70112
Primary Topic
Glycogen Storage Diseases and Myoclonus
Type
article
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article

Liver Involvement in POLG Disease—a Multicentre Cohort Study of 202 Patients

Heather Biggs, Omar Hikmat, Pirjo Isohanni, Magnhild Rasmussen et al.
Journal of Inherited Metabolic Disease
Glycogen Storage Diseases and Myoclonus
article

Liver Involvement in POLG Disease—a Multicentre Cohort Study of 202 Patients

Heather Biggs, Omar Hikmat, Pirjo Isohanni, Magnhild Rasmussen, Leticia Pías‐Peleteiro, Emma Harrison, Rita Horváth, Carolyn M. Sue, Martin Engvall, Shamima Rahman, K Naess, Johanna Uusimaa, Siren Berland, Mika Henrik Martikainen, Mikko Kärppä, Niklas Darín, Erle Kristensen, Elsebet Østergaard, Juan Darío Ortigoza‐Escobar, Kari Majamaa, Eylert Brodtkorb, Claus Klingenberg, Trine Tangeraas, Judith S. Walker, I.F.M. de Coo
article en

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.

Journal of Inherited Metabolic DiseaseVol. 48(6)
University of Copenhagen (DK), Oslo University Hospital (NO), University Hospital of North Norway (NO), Hospital Sant Joan de Déu Barcelona (ES), Karolinska University Hospital (SE), University of Helsinki (FI), Norwegian University of Science and Technology (NO), University of Cambridge (GB), Oulu University Hospital (FI), Great Ormond Street Hospital for Children NHS Foundation Trust (GB), Helsinki University Hospital (FI), Haukeland University Hospital (NO), Sahlgrenska University Hospital (SE), Turku University Hospital (FI), Copenhagen University Hospital (DK), Rigshospitalet (DK), Karolinska Institutet (SE), Maastricht University (NL), Helsinki Children's Hospital (FI), St Olav's University Hospital (NO), Sant Joan de Déu Research Foundation (ES), South Eastern Sydney Local Health District (AU), University of Bergen (NO), University College London (GB), UiT The Arctic University of Norway (NO), Neuroscience Research Australia (AU), University of Oulu (FI)
Openalex Percentile: Top 51%
Glycogen Storage Diseases and Myoclonus
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