title: Multiple Acyl-CoA Dehydrogenation Deficiency (Glutaric Aciduria Type II) with a Novel Mutation of Electron Transfer Flavoprotein-Dehydrogenase in a Cat.
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.
authors.affiliation: Laboratory of Veterinary Biochemistry and Molecular Biology, Faculty of Agriculture, University of Miyazaki, Miyazaki, Japan.
authors.forename: Shoichi
authors.initials: S
authors.lastname: Wakitani
authors.forename: Shidow
authors.initials: S
authors.lastname: Torisu
authors.forename: Taiki
authors.initials: T
authors.lastname: Yoshino
authors.forename: Kazuhisa
authors.initials: K
authors.lastname: Hattanda
authors.forename: Osamu
authors.initials: O
authors.lastname: Yamato
authors.forename: Ryuji
authors.initials: R
authors.lastname: Tasaki
authors.forename: Haruo
authors.initials: H
authors.lastname: Fujita
authors.forename: Koichiro
authors.initials: K
authors.lastname: Nishino