Development of a Mitochondrial Myopathy?Composite Assessment Tool

Background ‘Mitochondrial Myopathy’ (MM) refers to genetically-confirmed Primary Mitochondrial Disease (PMD) that predominantly impairs skeletal muscle function. Validated outcome measures encompassing core MM domains of weakness, fatigue, imbalance, impaired dexterity, and exercise intolerance do not exist. The goal this study was validate clinically-meaningful, quantitative specific MM. Methods This a single centre study. Objective evaluated included hand-held dynamometry, balance assessments, Nine Hole Peg Test (9HPT), Functional Dexterity (FDT), 30 second Sit Stand (30s STS), 6-minute walk test (6MWT). Results were assessed as z-scores, with < ?2 standard deviations considered abnormal. Performance relative the North Star Ambulatory Assessment (NSAA) functional mobility by Pearson's correlation. In participants [n = 59, mean age 21.6 ± 13.9 (range 7 – 64.6 years), 44.1% male], nuclear gene aetiologies, n 18/59, or mitochondrial (mtDNA) 41/59, dynamometry measurements demonstrated both proximal [dominant elbow flexion (?2.6 2.1, z-score deviation, SD), hip (?2.5 2.3), knee (?2.8 1.3)] distal weakness [wrist extension (?3.4 1.7), palmar pinch 2.8), ankle dorsiflexion (?2.4 2.5)]. Balance [Tandem Stance (TS) Eyes Open (?3.2 8.8, 53) TS Closed 2.7, 52)] dexterity [FDT (?5.9 6.0, 44) 9HPT (?8.3 11.2, 53)] assessments also revealed impairment. Exercise confirmed strength-based 30s STS (?2.0 0.8, 38) mobility-based 6MWT (?2.9 1.3, 46) significant decline in minute distances (slope ?0.9, p 0.03, 46). Muscle fatigue quantified repetitions strength decrement noted between first sixth at dominant flexors (?14.7 2.2%, error, SEM, 21). All incorporated MM-Composite Tool (MM-COAST). MM-COAST composite score for 1.3 0.1 (n higher indicating greater disease severity, correlated NSAA (r ?0.64, 0.0001, 52) indicate clinical meaning. Test–retest reliability an subset 14) intraclass correlation coefficient (ICC) 0.81 (95% confidence interval: 0.59–0.92) good reliability. Conclusions We have developed successfully validated MM-specific Composite quantify key MM, shown be abnormal Definite cohort. may hold particular utility meaningful measure future intervention trials.