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Original research
Advanced pathological study for definite diagnosis of mitochondrial cardiomyopathy
  1. Atsuhito Takeda1,
  2. Kei Murayama2,
  3. Yasushi Okazaki3,
  4. Atsuko Imai-Okazaki3,
  5. Akira Ohtake4,5,
  6. Emi Takakuwa6,
  7. Hirokuni Yamazawa1,
  8. Gaku Izumi1,
  9. Jiro Abe1,
  10. Ayako Nagai1,
  11. Kota Taniguchi1,
  12. Daisuke Sasaki1,
  13. Takao Tsujioka1,
  14. John M Basgen7
  1. 1 Department of Pediatrics, Faculty of Medicine and Graduate School of Medicine, Hokkaido University, Sapporo, Japan
  2. 2 Department of Metabolism, Chiba Children’s Hospital, Chiba, Japan
  3. 3 Diagnostics and Therapeutics of Intractable Diseases, Intractable Disease Research Center, Juntendo University School of Medicine Graduate School of Medicine, Bunkyo-ku, Tokyo, Japan
  4. 4 Department of Pediatrics & Clinical Genomics, Saitama Medical University Faculty of Medicine, Saitama, Japan
  5. 5 Center for Intractable Diseases, Saitama Medical University, Saitama, Japan
  6. 6 Department of Surgical Pathology, Hokkaido University Hospital, Sapporo, Japan
  7. 7 Department of Research, Charles R Drew University of Medicine and Science, Los Angeles, California, USA
  1. Correspondence to Dr Atsuhito Takeda, Pediatrics, Hokkaido University, Sapporo, Japan; a-takeda{at}med.hokudai.ac.jp

Abstract

Aims Mitochondrial cardiomyopathy (MCM) is difficult to make a definite diagnosis because of various cardiovascular phenotypes and no diagnostic criteria in the pathology examination. We aim to add myocardial pathology to the diagnostic criteria for mitochondrial respiratory chain disorders.

Methods Quantitative analysis of mitochondria using electron microscopy and immunohistopathological analysis with respiratory chain enzyme antibodies were performed in 11 patients with hypertrophic or restrictive cardiomyopathy who underwent endomyocardial biopsy for possible MCM . Respiratory chain enzymatic assay in biopsied myocardium and genetic studies were also performed in all the subjects to define MCM.

Results Four patients were diagnosed with MCM according to the recent criteria of mitochondrial respiratory chain disorders. Using electron microscopy with quantitative analysis, the volume density of mitochondria within cardiac muscle cells was significantly increased in the MCM group compared with the non-MCM group (p=0.007). Immunohistopathological results were compatible with the result of the respiratory chain enzymatic assay.

Conclusions Pathological diagnosis of MCM could be confirmed by a quantitative study of electron microscopy and immunohistopathological analysis using the mitochondrial respiratory chain enzyme subunit antibody.

  • cardiovascular diseases
  • microscopy, electron
  • morphological and microscopic findings
  • immunohistochemistry

Data availability statement

Data are available in a public, open access repository. The data that support the findings of this study are available from the corresponding author on reasonable request.

https://doi.org/10.1136/jclinpath-2020-206801

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    Data availability statement

    Data are available in a public, open access repository. The data that support the findings of this study are available from the corresponding author on reasonable request.

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    Footnotes

    • Handling editor Runjan Chetty.

    • Contributors AT designed the study, performed the analysis and interpretation of data, and wrote the initial draft of the manuscript. JMB supervised the morphometric analysis and helped to revise the manuscript. KM, YO, AI-O and AO contributed to the biochemical and the genetic diagnosis of mitochondrial respiratory chain disorder. ET provided the immunohistopathological image. HY, GI, JA, AN, KT, DS and TT substantially contributed to clinical data acquisition. All authors edited the manuscript and approved the final version.

    • Funding This research was partially supported by the Practical Research Project (19ek0109273, 20ek0109468) for Rare/Intractable Diseases from the Japan Agency for Medical Research and Development, AMED to AT and KM.

    • Competing interests None declared.

    • Provenance and peer review Not commissioned; externally peer reviewed.