Myoclonic epilepsy and ragged-red fibers with cytochrome oxidase deficiency: neuropathology, biochemistry, and molecular genetics.

TitleMyoclonic epilepsy and ragged-red fibers with cytochrome oxidase deficiency: neuropathology, biochemistry, and molecular genetics.
Publication TypeJournal Article
Year of Publication1989
AuthorsLombès, A, Mendell, JR, Nakase, H, Barohn, RJ, Bonilla, E, Zeviani, M, Yates, AJ, Omerza, J, Gales, TL, Nakahara, K
JournalAnn Neurol
Volume26
Issue1
Pagination20-33
Date Published1989 Jul
ISSN0364-5134
KeywordsAdolescent, Adult, Ataxia, Child, Cytochrome-c Oxidase Deficiency, Epilepsies, Myoclonic, Female, Humans, Male, Middle Aged, Mitochondria, Muscular Diseases, Pedigree
Abstract

A 36-year-old man with myoclonic epilepsy and ragged-red fibers (MERRF) died after more than 18 years of follow-up study. He was 1 of 3 affected siblings and the offspring of an affected mother, suggesting maternal transmission. At autopsy, there was neuronal loss and gliosis in the dentate nucleus of the cerebellum and in the inferior olivary nucleus. Skeletal muscle showed ragged-red fibers, and paracrystalline inclusions in mitochondria by electron microscopy. Biochemical analysis showed a generalized partial defect of cytochrome c oxidase (COX) in mitochondria isolated from all tissues, including brain, heart, skeletal muscle, kidney, and liver. The Michaelis constant (Km) for cytochrome c was abnormally low, suggesting a defect of the mitochondrially encoded subunit II of COX. Immunological studies (enzyme-linked immunosorbent assay, dot-blot, Western blot, and immunohistochemistry) showed that the holoenzyme was decreased but subunit II was decreased more than the holocomplex or the nuclearly encoded subunit IV. However, Northern and Southern blots showed that the gene for subunit II, as well as the genes for subunits I, III, IV, and VIII, were of normal size and were normally transcribed. A point mutation or a small deletion of mitochondrial DNA, probably affecting the COX-II gene, may be responsible for the COX deficiency in this case of MERRF.

DOI10.1002/ana.410260104
Alternate JournalAnn. Neurol.
Citation Key10.1002/ana.410260104
PubMed ID2549843
Grant ListNS 11766 / NS / NINDS NIH HHS / United States