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.
Funding source: Japan Agency for Medical Research and Development
Award Identifier / Grant number: 18ek0109273
Award Identifier / Grant number: 18ek0109177
Award Identifier / Grant number: 17ek0109088h00
Funding source: Ministry of Education, Culture, Sports, Science and Technology
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.
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.
Employment or leadership: None declared.
Honorarium: None declared.
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).
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