Acquired multiple Acyl-CoA dehydrogenase deficiency in 10 horses with atypical myopathy.
The aim of the current study was to assess lipid metabolism in horses with atypical myopathy. Urine samples from 10 cases were subjected to analysis of organic acids, glycine conjugates, and acylcarnitines revealing increased mean excretion of lactic acid, ethylmalonic acid, 2-methylsuccinic acid, butyrylglycine, (iso)valerylglycine, hexanoylglycine, free carnitine, C2-, C3-, C4-, C5-, C6-, C8-, C8:1-, C10:1-, and C10:2-carnitine as compared with 15 control horses (12 healthy and three with acute myopathy due to other causes). Analysis of plasma revealed similar results for these predominantly short-chain acylcarnitines. Furthermore, measurement of dehydrogenase activities in lateral vastus muscle from one horse with atypical myopathy indeed showed deficiencies of short-chain acyl-CoA dehydrogenase (0.66 as compared with 2.27 and 2.48 in two controls), medium-chain acyl-CoA dehydrogenase (0.36 as compared with 4.31 and 4.82 in two controls) and isovaleryl-CoA dehydrogenase (0.74 as compared with 1.43 and 1.61 nmol min(-1) mg(-1) in two controls). A deficiency of several mitochondrial dehydrogenases that utilize flavin adenine dinucleotide as cofactor including the acyl-CoA dehydrogenases of fatty acid beta-oxidation, and enzymes that degrade the CoA-esters of glutaric acid, isovaleric acid, 2-methylbutyric acid, isobutyric acid, and sarcosine was suspected in 10 out of 10 cases as the possible etiology for a highly fatal and prevalent toxic equine muscle disease similar to the combined metabolic derangements seen in human multiple acyl-CoA dehydrogenase deficiency also known as glutaric acidemia type II.
Westermann
C M
CM
Department of Equine Sciences, Medicine Section, Faculty of Veterinary Medicine, Utrecht University, Yalelaan 114, 3508 TD Utrecht, The Netherlands.
Dorland
L
L
Votion
D M
DM
de Sain-van der Velden
M G M
MG
Wijnberg
I D
ID
Wanders
R J A
RJ
Spliet
W G M
WG
Testerink
N
N
Berger
R
R
Ruiter
J P N
JP
van der Kolk
J H
JH
D042964:Acyl-CoA Dehydrogenase / Q000172:deficiency / Q000378:metabolism; D044944:Acyl-CoA Dehydrogenases / Q000172:deficiency* / Q000378:metabolism; D000818:Animals; D020148:Butyric Acid / Q000097:blood / Q000652:urine; D044926:Butyryl-CoA Dehydrogenase / Q000172:deficiency / Q000378:metabolism; D002331:Carnitine / Q000031:analogs & derivatives / Q000097:blood / Q000652:urine; D002851:Chromatography, High Pressure Liquid; D005260:Female; D008401:Gas Chromatography-Mass Spectrometry; D005977:Glutarates / Q000097:blood / Q000652:urine; D006734:Horse Diseases / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology; D006736:Horses; D050769:Isovaleryl-CoA Dehydrogenase / Q000172:deficiency / Q000378:metabolism; D019344:Lactic Acid / Q000097:blood / Q000652:urine; D008297:Male; D008854:Microscopy, Electron; D008856:Microscopy, Fluorescence; D009132:Muscles / Q000473:pathology / Q000648:ultrastructure; D009135:Muscular Diseases / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology; D012256:Riboflavin / Q000097:blood
D005977:Glutarates; C116917:acylcarnitine; D020148:Butyric Acid; D019344:Lactic Acid; D044944:Acyl-CoA Dehydrogenases; D044926:Butyryl-CoA Dehydrogenase; D050769:Isovaleryl-CoA Dehydrogenase; D042964:Acyl-CoA Dehydrogenase; C035736:glutaric acid; D002331:Carnitine; D012256:Riboflavin