Progressive External Ophthalmoplegia

Abstract

Muscle biopsies from four patients with chronic progressive external ophthalmoplegia and pigmentary retinopathy with symptoms and signs from other organs 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. Blood levels of lactate and pyruvate were measured and abnormal values of these metabolites were found in the three patients with the most pronounced ultrastructural changes. On the basis of these findings it is suggested that there is a biochemical defect in pyruvate-lactate metabolism which could be responsible for the marked proliferation of the abnormal mitochondria.

Mitochondrial Chronic Progressive External Ophthalmoplegia

“…POLG consists of one catalytic subunit and two subunits encoded from POLG2. (5) The removal of RNA primers and flap intermediates is then achieved via ribonuclease H1 (RNase H1), DNA helicase/ nuclease 2 (DNA2), and mitochondrial genome maintenance exonuclease 1 (MGME1). ( 6) Mitochondrial fusion is mediated by the proteins optic atrophy 1 (OPA1), F-box and leucine-rich repeat 4 (FBXL4), mitofusin 1 and 2 (MFN 1 and 2).…”

“…Von Graefe, in 1868, originally described CPEO, and later, in 1958, Kearns and Sayre first described their triad of CPEO, retinal degeneration, and heart block (Kearns-Sayre syndrome) [2]. Microscopical findings of pathological mitochondria in 1967 and ragged red fibers in 1972 [3,4], as well as increased venous pyruvate and lactate in 1976 [5], were significant in understanding the disease's path. More recently, singular and multiple mitochondrial DNA (mtDNA) deletions were detected in 1988 and 1989 [6,7].…”

“…Mitochondrial DNA synthesis (4) requires the enzymes TWINKLE, a helicase, and the synthesis initiator, DNA polymerase gamma (POLG), which needs an RNA primer that is supplied by mitochondrial transcription factor A (TFAM). POLG consists of one catalytic subunit and two subunits encoded from POLG2 (5). The removal of RNA primers and flap intermediates is then achieved via ribonuclease H1 (RNase H1), DNA helicase/ nuclease 2 (DNA2), and mitochondrial genome maintenance exonuclease 1 (MGME1).…”