Epidemiology and natural history of POLG disease in Norway: a nationwide cohort study

Abstract

Abstract Objective To investigate the prevalence and natural history of POLG disease in the Norwegian population. Methods A national, population‐based, retrospective study using demographic, clinical, and genetic data of patients with genetically confirmed POLG disease. The patients were diagnosed between 2002 and 2022, and were included into the Norwegian POLG Patient Registry. Patients were stratified according to age at disease onset (early <12 years, juvenile to adult 12–40 years, late ≥40 years) and resident region. Results Ninety‐one patients were included. The point prevalence of POLG disease was 1:149,253. Birth prevalence was 1:48,780. Median age at clinical onset was 16 years (range: 2 months to 70 years). Onset occurred early in 35% (32 out of 91), juvenile‐adult in 55% (50 out of 91) and late in 10% (9 out of 91). A distinct seasonal pattern in disease onset was observed, with 57% (52 out of 91) presenting between May and August. Forty‐five patients (49%) had acute exacerbations that required intensive care, and this affected 72% of those in the early‐onset group. The mortality rate was 54% (49 out of 91), with a median time from disease onset to death of 3 years (range: 1 month to 36 years). Interpretation We provide the point prevalence and birth prevalence of POLG disease in the first nationwide study in which epidemiological and clinical data were integrated. Seasonal variations in clinical onset may offer valuable insights into disease mechanisms and modifying factors. The findings from this study are crucial for quantifying the disease burden, and contribute to evidence‐based healthcare planning.