Cytochrome c oxidase deficiency in leigh syndrome

Authors

  • Dr Salvatore DiMauro,

    MD, Corresponding author
    1. H. Houston Merritt Clinical Research Center for Muscular Dystrophy and Related Diseases, and the Division of Pediatric Neurology, Columbia University College of Physicians and Surgeons, New York, NY
    • 4-420, College of Physicians and Surgeons, 630 West 168 St, New York, NY 10032
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  • Serenella Servidei,

    MD
    1. H. Houston Merritt Clinical Research Center for Muscular Dystrophy and Related Diseases, and the Division of Pediatric Neurology, Columbia University College of Physicians and Surgeons, New York, NY
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  • Massimo Zeviani,

    MD
    1. H. Houston Merritt Clinical Research Center for Muscular Dystrophy and Related Diseases, and the Division of Pediatric Neurology, Columbia University College of Physicians and Surgeons, New York, NY
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  • Maja DiRocco,

    MD
    1. H. Houston Merritt Clinical Research Center for Muscular Dystrophy and Related Diseases, and the Division of Pediatric Neurology, Columbia University College of Physicians and Surgeons, New York, NY
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  • Darryl C. DeVivo,

    MD
    1. H. Houston Merritt Clinical Research Center for Muscular Dystrophy and Related Diseases, and the Division of Pediatric Neurology, Columbia University College of Physicians and Surgeons, New York, NY
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  • Stefano DiDonato,

    MD
    1. Istituto Neurologico “C. Besta,” Milan, Italy
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  • Graziella Uziel,

    MD
    1. Istituto Neurologico “C. Besta,” Milan, Italy
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  • Kenneth Berry,

    MD
    1. Vancouver General Hospital, Vancouver, BC, Canada
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  • George Hoganson,

    MD
    1. Clinical Genetics Center, University of Wisconsin, Madison, WI
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  • Stanley D. Johnsen,

    MD
    1. Barrow Neurological Institute, St. Joseph's Hospital and Medical Center, Phoenix, AZ
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  • Peter C. Johnson

    MD
    1. Barrow Neurological Institute, St. Joseph's Hospital and Medical Center, Phoenix, AZ
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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 (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.

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