title: Equine biochemical multiple acyl-CoA dehydrogenase deficiency (MADD) as a cause of rhabdomyolysis.
abstract: Two horses (a 7-year-old Groninger warmblood gelding and a six-month-old Trakehner mare) with pathologically confirmed rhabdomyolysis were diagnosed as suffering from multiple acyl-CoA dehydrogenase deficiency (MADD). This disorder has not been recognised in animals before. Clinical signs of both horses were a stiff, insecure gait, myoglobinuria, and finally recumbency. Urine, plasma, and muscle tissues were investigated. Analysis of plasma showed hyperglycemia, lactic acidemia, increased activity of muscle enzymes (ASAT, LDH, CK), and impaired kidney function (increased urea and creatinine). The most remarkable findings of organic acids in urine of both horses were increased lactic acid, ethylmalonic acid (EMA), 2-methylsuccinic acid, butyrylglycine (iso)valerylglycine, and hexanoylglycine. EMA was also increased in plasma of both animals. Furthermore, the profile of acylcarnitines in plasma from both animals showed a substantial elevation of C4-, C5-, C6-, C8-, and C5-DC-carnitine. Concentrations of acylcarnitines in urine of both animals revealed increased excretions of C2-, C3-, C4-, C5-, C6-, C5-OH-, C8-, C10:1-, C10-, and C5-DC-carnitine. In addition, concentrations of free carnitine were also increased. Quantitative biochemical measurement of enzyme activities in muscle tissue showed deficiencies of short-chain acyl-CoA dehydrogenase (SCAD), medium-chain acyl-CoA dehydrogenase (MCAD), and isovaleryl-CoA dehydrogenase (IVD) also indicating MADD. Histology revealed extensive rhabdomyolysis with microvesicular lipidosis predominantly in type 1 muscle fibers and mitochondrial damage. However, the ETF and ETF-QO activities were within normal limits indicating the metabolic disorder to be acquired rather than inherited. To our knowledge, these are the first cases of biochemical MADD reported in equine medicine.
authors.affiliation: Department of Equine Sciences, Medicine Section, Faculty of Veterinary Medicine, Utrecht University, Yalelaan 112, P.O. Box 80.152, 3508 TD Utrecht, The Netherlands.
authors.forename: C M
authors.initials: CM
authors.lastname: Westermann
authors.forename: M G M
authors.initials: MG
authors.lastname: de Sain-van der Velden
authors.forename: J H
authors.initials: JH
authors.lastname: van der Kolk
authors.forename: R
authors.initials: R
authors.lastname: Berger
authors.forename: I D
authors.initials: ID
authors.lastname: Wijnberg
authors.forename: J P
authors.initials: JP
authors.lastname: Koeman
authors.forename: R J A
authors.initials: RJ
authors.lastname: Wanders
authors.forename: J A
authors.initials: JA
authors.lastname: Lenstra
authors.forename: N
authors.initials: N
authors.lastname: Testerink
authors.forename: A B
authors.initials: AB
authors.lastname: Vaandrager
authors.forename: C
authors.initials: C
authors.lastname: Vianey-Saban
authors.forename: C
authors.initials: C
authors.lastname: Acquaviva-Bourdain
authors.forename: L
authors.initials: L
authors.lastname: Dorland
mesh_terms: D042964:Acyl-CoA Dehydrogenase / Q000172:deficiency* / Q000235:genetics; D000818:Animals; D005260:Female; D006734:Horse Diseases / Q000201:enzymology* / Q000473:pathology; D006736:Horses; D008297:Male; D012206:Rhabdomyolysis / Q000201:enzymology / Q000473:pathology / Q000662:veterinary*
chemical_list: D042964:Acyl-CoA Dehydrogenase