Abstract
Multiple acyl-CoA dehydrogenation deficiency (MADD; also known as glutaric aciduria type II) is a human autosomal recessive disease classified as one of the mitochondrial fatty-acid oxidation disorders. MADD is caused by a defect in the electron transfer flavoprotein (ETF) or ETF dehydrogenase (ETFDH) molecule, but as yet, inherited MADD has not been reported in animals. Here we present the first report of MADD in a cat. The affected animal presented with symptoms characteristic of MADD including hypoglycemia, hyperammonemia, vomiting, diagnostic organic aciduria, and accumulation of medium- and long-chain fatty acids in plasma. Treatment with riboflavin and l-carnitine ameliorated the symptoms. To detect the gene mutation responsible for MADD in this case, we determined the complete cDNA sequences of feline ETFα, ETFβ, and ETFDH. Finally, we identified the feline patient-specific mutation, c.692T>G (p.F231C) in ETFDH. The affected animal only carries mutant alleles of ETFDH. p.F231 in feline ETFDH is completely conserved in eukaryotes, and is located on the apical surface of ETFDH, receiving electrons from ETF. This study thus identified the mutation strongly suspected to have been the cause of MADD in this cat.
Competing interests: None declared
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Acknowledgments
The authors sincerely thank the owners of the studied cats for their participation. We are grateful to MILS INTERNATIONAL for GC-MS analysis of urine organic acids. This study was supported by a Grant-in-Aid from University of Miyazaki (3901020300: to KN) and a Grant-in-Aid from the Japan Society for the Promotion of Science (KAKENHI-B 25292187: to KN).
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Communicated by: Jerry Vockley, M.D., Ph.D.
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Synopsis
We discovered the first case of MADD in a cat.
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Shoichi Wakitani, Shidow Torisu, Taiki Yoshino, Kazuhisa Hattanda, Osamu Yamato, Ryuji Tasaki, Haruo Fujita, and Koichiro Nishino declare that they have no conflicts of interest. This article does not contain any studies with human subjects performed by the any of the authors. All institutional and national guidelines for the care and use of laboratory animals were followed. The work presented here was carried out in collaboration between all authors. SW and KN conceived and designed this experiment, analyzed a gene mutation, and wrote this article. ST and KH diagnosed the cat. TY conducted DNA sequencing; OY, RT, and HF conducted LC-MS/MS analysis.
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Wakitani, S. et al. (2013). Multiple Acyl-CoA Dehydrogenation Deficiency (Glutaric Aciduria Type II) with a Novel Mutation of Electron Transfer Flavoprotein-Dehydrogenase in a Cat. In: Zschocke, J., Gibson, K., Brown, G., Morava, E., Peters, V. (eds) JIMD Reports - Case and Research Reports, Volume 13. JIMD Reports, vol 13. Springer, Berlin, Heidelberg. https://doi.org/10.1007/8904_2013_268
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DOI: https://doi.org/10.1007/8904_2013_268
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