Progressive external ophthalmoplegia. Evidence for a generalized mitochondrial disease with a defect in pyruvate metabolism

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Surv Ophthalmol

22 (6) May-June

CURRRNTOPHTHALMOLOGY

1978

Progressive External Ophthalmoplegia. Evidence for a Generalized Mitochondrial Disease with a Defect in Pyruvate Metabolism, by E. Reske-Nielsen, H.C. Lou and M. Lowes. Acta Ophthalmol 54:553-513, 1976 Chronic progressive external ophthalmoplegia (CPEO) associated with signs of systemic involvement is a well-recognized clinical entity. There has been much discussion as to whether the ophthalmoplegia represents a myopathy or a neuropathy. Muscle biopsies from four such patients were studied by means of light and electron microscopy. Examination revealed a marked proliferation of abnormal mitochondria with a degeneration of both muscle and nerve tissue. Large and bizarre mitochondria with complicated inclusions were found in muscle cells, Iibroblasts and blood vessel endothelial cells, indicating that the abnormality is universal. The organs involved - striated muscles (in particular, extraocular muscles), myocardium, retina (pigment epithelium), central nervous system, and the endocrine organs - characteristically have a high rate of energy consumption in which pyruvate metabolism plays a key role. Pyruvate metabolism was therefore studied and the blood levels of pyruvate and lactate were measured. Increased levels of these metabolites were found in the three patients who had the most pronounced ultrastructural alterations in the biopsies. The findings suggest a defect in pyruvate metabolism. The enzyme systems involved are located in the mitochondrial cristae, and it is considered that the proposed defect in pyruvate metabolism could be the primary factor responsible for the proliferation of the abnormal mitochondria. (Abstract by E. Reske-Nielsen)

Comment This study presents further evidence indicating that chronic progressive external ophthalmoplegia (CPEO) is a disease involving many organ systems. The authors have once again demonstrated the existence of abnormal mitochondria in affected patients and compared their findings with normal “controls” from an earlier study. Furthermore, they have made a new and perhaps important observation that patients with CPEO have increased blood levels of pyruvate and lactate. Since the enzymes responsible for the metabolism of these substances are located within mitochondria they have proposed that a biochemical defect within the Krebs cycle is responsible for the abnormal mitochondria. Several questions arise: Are the mitochondrial abnormalities specifically related to CPEO or are they an aging change? What effect does age have on blood levels of pyruvate and lactate? These questions could be answered in part if blood pyruvate levels and muscle biopsies for electron microscopy were performed on age-matched controls and CPEO patients. THOMASWEINGEIST