Mitochondrial Myopathy

Mitochondrial myopathies are disorders of oxidative phosphorylation due to mitochondrial or nuclear DNA mutations, affecting skeletal muscle with or without other organs.

• Prevalence about 1 in 5,000.

• Syndromes: chronic progressive external ophthalmoplegia (CPEO, single deletion), Kearns-Sayre syndrome, MELAS (m.3243A>G), MERRF (m.8344A>G), Leigh syndrome, mitochondrial neurogastrointestinal encephalomyopathy (TYMP).

• Maternal inheritance (mtDNA point mutations) or sporadic (deletions); heteroplasmy modifies severity.

• Exercise intolerance, myalgia, proximal weakness, ptosis, ophthalmoplegia (no diplopia).

• Multisystem: sensorineural hearing loss, diabetes, cardiomyopathy, conduction block, short stature, migraine, seizures, stroke like episodes, lactic acidosis.

• Retinitis pigmentosa, optic atrophy, gastrointestinal dysmotility.

• Elevated resting or post exercise lactate, CK variable; CSF lactate.

• Muscle biopsy: ragged red fibres (Gomori trichrome), COX negative fibres, SDH hyperreactivity.

• Genetic testing: mtDNA sequencing and deletion analysis from blood, urine or muscle; nuclear gene panels (POLG, TK2).

• Cardiac, endocrine, audiology, ophthalmology evaluation; brain MRI.

• Exclude other metabolic myopathies (Pompe, McArdle, carnitine).

• No curative therapy; multidisciplinary care.

• Supplements (limited evidence): coenzyme Q10 200 to 400 mg/day, riboflavin 100 mg, L-carnitine 1 to 2 g/day, creatine; arginine (0.5 g/kg IV for acute stroke like episodes in MELAS, 150 to 300 mg/kg/day orally for prevention).

• Avoid valproate, aminoglycosides, linezolid, metformin cautiously, propofol prolonged infusions.

• Exercise: supervised aerobic training improves function.

• Cardiology: pacemaker for conduction block (Kearns-Sayre), heart failure therapy; diabetes (insulin), hearing aids or cochlear implants, ptosis surgery (crutches).

• Seizures: levetiracetam; avoid valproate.

• Genetic counselling, mitochondrial donation options.