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Licensed Unlicensed Requires Authentication Published by De Gruyter September 2, 2019

Successful treatment of infantile-onset ACAD9-related cardiomyopathy with a combination of sodium pyruvate, beta-blocker, and coenzyme Q10

  • Takumi Kadoya , Azumi Sakakibara , Kana Kitayama , Yuki Yamada , Shinji Higuchi , Rie Kawakita , Yuki Kawasaki , Mitsuhiro Fujino , Yosuke Murakami , Masaru Shimura , Kei Murayama , Akira Ohtake , Yasushi Okazaki , Yasutoshi Koga and Tohru Yorifuji EMAIL logo

Abstract

Mitochondrial acyl-CoA dehydrogenase 9 (ACAD9) deficiency is one of the common causes of respiratory chain complex I deficiency, which is characterized by cardiomyopathy, lactic acidemia, and muscle weakness. Infantile cardiomyopathy is the most common phenotype and is usually lethal by the age of 5 years. Riboflavin treatment is known to be effective in ~65% of the patients; however, the remaining are unresponsive to riboflavin and are in need of additional treatment measures. In this report, we describe a patient with ACAD9 deficiency who developed progressive cardiomyopathy at 8 months of age. As the patient’s left ventricular ejection fraction (LVEF) kept decreasing to 45.4% at 1 year 8 months, sodium pyruvate treatment was introduced together with a beta-blocker and coenzyme Q10. This resulted in a steady improvement, with full and sustained normalization of cardiac function without riboflavin. The therapy, therefore, might be a useful addition for the treatment of ACAD9 deficiency.


Corresponding author: Tohru Yorifuji, MD, PhD, Division of Pediatric Endocrinology and Metabolism, Children’s Medical Center, Osaka City General Hospital, 2-13-22 Miyakojima-hondori, Miyakojima, Osaka 534-0021, Japan; and Department of Genetic Medicine, Osaka City General Hospital, Osaka, Japan, Phone: +81-6-6929-1221, Fax: +81-6-6929-1090

Award Identifier / Grant number: 18ek0109273

Award Identifier / Grant number: 18ek0109177

Award Identifier / Grant number: 17ek0109088h00

Award Identifier / Grant number: 18k07895

Award Identifier / Grant number: 25461571

Funding statement: This work was supported by grants from the Japan Agency for Medical Research and Development (AMED) to K.M., A.O., Y.O. (18ek0109273, 18ek0109177, Funder Id: http://dx.doi.org/10.13039/100009619), and Y.K. (17ek0109088h00, Funder Id: http://dx.doi.org/10.13039/100009619); and from the Ministry of Education, Culture, Sports, Science and Technology (MEXT) to T.Y. (18k07895) and Y.K. (25461571). Y.O. and A.O. were also supported by grants from the Strategic Research Center in Private Universities from MEXT. The authors confirm independence from the sponsors; the content of the article has not been influenced by the sponsors.

Acknowledgments

We thank the patient and her family for their participation in the study.

  1. Author contributions: T.K. assembled the data and wrote the manuscript. A.S., K.K., Y.Y., S.H., and R.K. were involved in the sodium pyruvate treatment and collected clinical data. Y.K., M.F., and Y.M. collected and analyzed the data pertaining to cardiomyopathy. M.S., K.M., and A.O. performed biochemical analysis of fibroblasts and Y.O. performed exome sequencing. Y.K. reviewed the sodium pyruvate treatment. T.Y. formulated the whole project and wrote part of the manuscript.

  2. Employment or leadership: None declared.

  3. Honorarium: None declared.

  4. Competing interest statement: The authors have no competing interests to disclose.

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Supplementary Material

The online version of this article offers supplementary material (https://doi.org/10.1515/jpem-2019-0205).


Received: 2019-05-07
Accepted: 2019-07-16
Published Online: 2019-09-02
Published in Print: 2019-10-25

©2019 Walter de Gruyter GmbH, Berlin/Boston

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