The diagnosis of
mitochondrial myopathy depends upon a constellation of findings, family history, type of muscle involvement, specific laboratory abnormalities, and the results of histological, pathobiochemical and genetic analysis. In the present paper, the authors describe the diagnostic approach to
mitochondrial myopathies manifesting as extraocular muscle disease. The most common ocular manifestation of
mitochondrial myopathy is
progressive external ophthalmoplegia (PEO). To exclude
myasthenia gravis, ocular myositis, thyroid associated orbitopathy,
oculopharyngeal muscular dystrophy, and
congenital fibrosis of the extraocular muscles in patients with an early onset or long-lasting very slowly progressive ptosis and
external ophthalmoplegia, almost without any
diplopia, and normal to mildly elevated serum
creatine kinase and
lactate, electromyography, nerve conduction studies and MRI of the orbits should be performed. A PEO phenotype forces one to look comprehensively for other multisystemic mitochondrial features (e.g., exercise induced weakness,
encephalopathy,
polyneuropathy, diabetes,
heart disease). Thereafter, and presently even in familiar PEO, a diagnostic muscle biopsy should be taken. Histological and ultrastructural hallmarks are mitochondrial proliferations and structural abnormalities,
lipid storage, ragged-red fibers, or
cytochrome-C negative myofibers. In addition, Southern blotting may reveal the common deletion, or molecular analysis may verify specific mutations of distinct mitochondrial or nuclear genes.