A new mitochondria-related disease showing myopathy with episodic hyper-creatine kinase-emia

Authors

  • Yuji Okamoto MD, PhD,

    1. Department of Neurology and Geriatrics, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, Japan
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  • Itsuro Higuchi MD,

    1. Department of Neurology and Geriatrics, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, Japan
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  • Yusuke Sakiyama MD,

    1. Department of Neurology and Geriatrics, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, Japan
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  • Shoko Tokunaga MD,

    1. Department of Neurology and Geriatrics, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, Japan
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  • Osamu Watanabe MD, PhD,

    1. Department of Neurology and Geriatrics, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, Japan
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  • Kimiyoshi Arimura MD,

    1. Okatsu Neurology and Rehabilitation Hospital, Kagoshima, Japan
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  • Masanori Nakagawa MD,

    1. Department of Neurology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan
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  • Hiroshi Takashima MD, PhD

    Corresponding author
    1. Department of Neurology and Geriatrics, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, Japan
    • Professor and Chairman, Department of Neurology and Geriatrics, Kagoshima University, Graduate School of Medical and Dental Sciences, 8-35-1 Sakuragaoka, Kagoshima City, Kagoshima 890-8520, Japan
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Errata

This article is corrected by:

  1. Errata: Errata Volume 72, Issue 5, 825, Article first published online: November 2012

Abstract

Objective:

To elucidate the relationship between mitochondrial DNA (mtDNA) alterations and a mitochondrial disease with a distinct combination of characteristic symptoms, namely episodic hyper-creatine kinase (CK)-emia and mild myopathy.

Methods:

We selected 9 patients with mtDNA np8291 alteration from 586 patients suspected to have a mitochondrial disease, and assessed them clinically, pathologically, and genetically. These 9 patients had undiagnosed mitochondrial myopathy with episodic hyper-CK-emia, all showing similar symptoms and progression.

Results:

Patients had mild muscle weakness and episodic hyper-CK-emia triggered by infections or drugs. Five of 9 patients were initially diagnosed with other conditions, such as myasthenia gravis, polymyositis, viral myositis, and drug-induced myopathy, because these conditions were acute or subacute, and 9 patients showed the same 16 mtDNA alterations, which have been reported to be nonpathological polymorphisms. Muscle biopsy revealed ragged-red fibers, highly expressed succinate dehydrogenase staining fibers, and cytochrome c oxidase–deficient fibers. Because their mitochondrial sequence data was almost the same, and 9 patients live in widely separated cities in Japan, the alterations may have arisen from a single source.

Interpretation:

These findings suggest that mild myopathy with episodic hyper-CK-emia associated with some of the 16 mtDNA alterations or at least with their mitochondria, could be a novel mitochondrial disease. Therefore, we propose that this disease be named as “mitochondrial myopathy with episodic hyper-CK-emia (MIMECK).” These alterations could work concomitantly and probably modify the impact of medications or other environmental factors. We believe these findings provide an insight into a novel aspect of mitochondrial disease pathogenesis. ANN NEUROL 2011;70: 486–492.

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