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Mitochondrial diseases are a clinically diverse group of genetic disorders that often present to neurologists. Health related quality of life (HRQOL) is increasingly recognised as a fundamental patient based outcome measure in both clinical intervention and research. Generic outcome measures have been extensively validated to assess HRQOL across populations and different disease states. However, due to their inclusive construct, it is acknowledged that not all relevant aspects of a specific illness may be captured. Hence there is a need to develop disease specific HRQOL measures that centre on symptoms characteristic of a specific disease or condition and their impact. This study presents the initial conceptualisation, development and preliminary psychometric assessment (validity and reliability) of a mitochondrial disease specific HRQOL measure (Newcastle Mitochondrial Quality of life measure (NMQ)). NMQ is a valuable assessment tool and consists of 63 items within 16 unidimensional domains, each demonstrating good internal reliability (Cronbach’s α⩾0.83) and construct validity.

Purpose Mitochondrial disease is the most common neuromuscular disease and has a profound impact upon daily life, disease and longevity. Exercise therapy has been shown to improve mitochondrial function in patients with mitochondrial disease. However, no information exists about the level of habitual physical activity of people with mitochondrial disease and its relationship with clinical phenotype. Methods Habitual physical activity, genotype and clinical presentations were assessed in 100 patients with mitochondrial disease. Comparisons were made with a control group individually matched by age, gender and BMI. Results Patients with mitochondrial disease had significantly lower levels of physical activity in comparison to matched people without mitochondrial disease (steps/day; 6883±3944 vs. 9924±4088, p = 0.001). 78% of the mitochondrial disease cohort did not achieve 10,000 steps per day and 48%were classified as overweight or obese. Mitochondrial disease was associated with less breaks in sedentary activity (Sedentary to Active Transitions, % per day; 13±0.03 vs. 14±0.03, p = 0.001) and an increase in sedentary bout duration (bout lengths / fraction of total sedentary time; 0.206±0.044 vs. 0.187±0.026, p = 0.001). After adjusting for covariates, higher physical activity was moderately associated with lower clinical disease burden (steps / day; rs = −0.49; 95% CI −0.33, −0.63, P

Purpose: Single large-scale mitochondrial DNA deletions account for a quarter of mitochondrial disease cases and occur sporadically with unknown risk factors. Mitochondrial DNA deletions accumulate with age in many tissues. Primordial germ cells, the precursors of oocytes are made by our grandmothers, therefore we wanted to determine whether age of maternal grandmother is a risk factor for sporadic mitochondrial DNA deletions. Methods: Twenty-nine patients with sporadic single mitochondrial DNA deletions from the Newcastle UK cohort provided dates of birth for mothers and maternal grandmothers plus father and paternal grandmother (healthy controls). Results: Mean age for grandmothers at birth of a mother of an affected patient was 28.5 years (SD ± 6.9) for single mitochondrial DNA deletions maternal grandmothers and 28.2 years (SD ± 6.1) for healthy control paternal grandmothers. Conclusion: Maternal grandmother age is not a risk factor for sporadic mitochondrial DNA deletions, an important observation in a population where many women are delaying reproduction.

Introduction Rapid progress has been made in relation to our understanding of the molecular and genetic basis of many mitochondrial disorders. Yet despite this, avenues for therapeutic intervention are limited. Low levels of habitual physical activity have been recognised to have a strong negative relationship with muscle mitochondrial capacity, disease development and mortality. The aims of this study were to systematically assess habitual physical activity in a cohort of mitochondrial patients. Methods One hundred patients were enrolled in the study. Habitual physical activity was measured by a multisensor array and by completion of a self-report questionnaire. Disease severity was assessed using the Newcastle Mitochondrial Disability Adult Scale (NMDAS). Results Low levels of habitual physical activity were common. Seventy-eight per cent of the patients achieved less than nationally advised levels of physical activity (10 000 steps per day) and almost half had an average daily energy expenditure of less than 1.4 METS. Higher physical activity was associated with lower BMI and lower clinical disease burden. Conclusion Low levels of physical activity are prominent and constitute a significant and important modifiable risk factor in mitochondrial disease. These findings advocate the promotion of increased physical activity irrespective of genotype.

Introduction Mitochondrial diseases are a clinically multifarous group of genetic disorders with extensive phenotypic and disease burden variability. Health related quality of life (HRQoL) is increasingly recognised as a fundamental patient-based outcome measure in both clinical intervention and research. Generic HRQoL outcome measures have been extensively validated across populations and different disease states. Due to their inclusive construct not all relevant aspects of a specific illness may be captured. It is acknowledged that there is a need to develop disease-specific HRQoL measures that centre on symptoms characteristic of a specific disease or condition. This study presents the conceptualisation, development and assessment of a disease-specific HRQoL measure (Mito-QoL) for patients with mitochondrial cytopathies. Methods Domain and item content for the Mito-QoL was derived from semi-structured key-informant interviews and modified following piloting of the questionnaire by post. Items were eliminated with the use of standard psychometric criteria. Construct validity was assessed by comparing domain scores with similar Short Form 36 domains. Results Mito-QoL consists of 63 items within 16 unidimensional domains demonstrating excellent internal reliability (Cronbach9s α>0.74) and construct validity. Conclusion Mito-QoL is a valid and reliable disease-specific HRQoL measure which may be of use in clinical practice and research.