Cytochrome c oxidase deficiency in Leigh syndrome.

TitleCytochrome c oxidase deficiency in Leigh syndrome.
Publication TypeJournal Article
Year of Publication1987
AuthorsDiMauro, S, Servidei, S, Zeviani, M, Dirocco, M, DeVivo, DC, DiDonato, S, Uziel, G, Berry, K, Hoganson, G, Johnsen, SD
JournalAnn Neurol
Volume22
Issue4
Pagination498-506
Date Published1987 Oct
ISSN0364-5134
KeywordsBrain, Brain Diseases, Metabolic, Child, Preschool, Cytochrome-c Oxidase Deficiency, Female, Humans, Infant, Kidney, Leigh Disease, Liver, Male, Muscles, Myocardium
Abstract

We studied 6 mitochondrial enzymes in crude extracts and isolated mitochondria from 5 children with pathologically proven subacute necrotizing encephalomyelopathy (Leigh syndrome). Samples were taken from brain (5 patients), skeletal muscle (4 patients), liver (4 patients), kidney (4 patients), heart (1 patient), and cultured fibroblasts (3 patients). An isolated defect of cytochrome c oxidase (COX) activity was found in brain (decrease of activity to 15 to 39% of the normal mean), muscle (9 to 20%), kidney (1 to 67%), and in the 1 available heart (4%) from a patient with cardiopathy. COX activity was also decreased in liver of 3 patients (2 to 13% of normal) and in cultured fibroblasts of 2 patients (18 and 27%), but it was normal in both liver and fibroblasts from 1 patient. Immunotitration using polyclonal antibodies against human heart COX showed essentially normal amounts of cross-reacting enzyme protein in various tissues from different patients. Electrophoresis of COX immunoprecipitated from brain mitochondrial extracts showed normal patterns of COX subunits in 2 patients. This study confirms the theory that COX deficiency is an important cause of Leigh syndrome.

DOI10.1002/ana.410220409
Alternate JournalAnn. Neurol.
Citation Key10.1002/ana.410220409
PubMed ID2829705
Grant ListNS 11766 / NS / NINDS NIH HHS / United States