Identifying trajectories of fatigue in patients with primary mitochondrial disease due to the m.3243A > G variant

Severe fatigue is a common complaint in patients with primary mitochondrial disease. However, less is known about the course of fatigue over time. This longitudinal observational cohort study of patients with the mitochondrial DNA 3243 A>G variant explored trajectories of fatigue over 2 years, and characteristics of patients within these fatigue trajectories. Fifty-three adult patients treated at the Radboud University Medical Center Nijmegen were included. The majority of the patients reported consistent, severe fatigue (41%), followed by patients with a mixed pattern of severe and mild fatigue (36%). Then, 23% of patients reported stable mild fatigue levels. Patients with a stable high fatigue trajectory were characterized by higher disease manifestations scores, more clinically relevant mental health symptoms, and lower psychosocial functioning and quality of life compared to patients reporting stable low fatigue levels. Fatigue at baseline and disease manifestation scores predicted fatigue severity at the 2-year assessment (57% explained variance). This study demonstrates that severe fatigue is a common and stable complaint in the majority of patients. Clinicians should be aware of severe fatigue in patients with moderate to severe disease manifestation scores on the Newcastle Mitochondrial Disease Scale, the high prevalence of clinically relevant mental health symptoms and overall impact on quality of life in these patients. Screening of fatigue and psychosocial variables will guide suitable individualized treatment to improve the quality of life.

Automated summary

This study explores the trajectory of fatigue in patients with the mitochondrial DNA 3243 A>G variant over 2 years and finds that severe fatigue is a common and stable symptom in the majority of patients. Patients with a stable high fatigue trajectory show higher disease manifestations, more clinically relevant mental health symptoms, and lower psychosocial functioning and quality of life.