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5% in blood Sporadic Myopathy Mechanism Reduced Assembly of COX enzyme Reduced Anchoring of COX II in mitochondrial membrane G7970T mutation (E129X) Myopathy Many COX- fibers Severe reduction in COX activity (10% to 20% residual) Lipid in type I fibers Fiber size: Mild variation Cataracts Hearing loss: Sensory-neural Ataxia Cardiac arrhythmia Depression Short stature Lactic acidosis G8009A: Somatic mutation found in colorectal cancer Biochemistry Lactate: Mildly increased in serum or CSF Oxidative enzymes: Selective reduction in COX activity Muscle pathology COX deficiency in 97% of muscle fibers: All COX subunits reduced Mitochondrial proliferation: Increased SDH stain, mild to moderate Myopathy, Deafness & CNS disorders 41 Mitochondrial tRNA Ser(UCN) (MTTS1)

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95% CI, 0.520.90), despite significant heterogeneity among studies ( I 2 = 88%)