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Cytochrome c oxidase deficiency in leigh syndrome
Author(s) -
DiMauro Salvatore,
Servidei Serenella,
Zeviani Massimo,
DiRocco Maja,
DeVivo Darryl C.,
DiDonato Stefano,
Uziel Graziella,
Berry Kenneth,
Hoganson George,
Johnsen Stanley D.,
Johnson Peter C.
Publication year - 1987
Publication title -
annals of neurology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.764
H-Index - 296
eISSN - 1531-8249
pISSN - 0364-5134
DOI - 10.1002/ana.410220409
Subject(s) - cytochrome c oxidase , kidney , mitochondrion , pathology , polyclonal antibodies , medicine , endocrinology , leigh disease , enzyme , biology , antibody , biochemistry , immunology , mitochondrial dna , gene
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 (Decemberrease 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 Decemberreased 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.