title: Seasonal pasture myopathy/atypical myopathy in North America associated with ingestion of hypoglycin A within seeds of the box elder tree.
abstract: BACKGROUND
  We hypothesised that seasonal pasture myopathy (SPM), which closely resembles atypical myopathy (AM), was caused by ingestion of a seed-bearing plant abundant in autumn pastures.
  
  
  OBJECTIVE
  To identify a common seed-bearing plant among autumn pastures of horses with SPM, and to determine whether the toxic amino acid hypoglycin A was present in the seeds and whether hypoglycin metabolites were present in SPM horse serum or urine.
  
  
  METHODS
  Twelve SPM cases, 11 SPM pastures and 23 control farms were visited to identify a plant common to all SPM farms in autumn. A common seed was analysed for amino acid composition (n = 7/7) by GC-MS and its toxic metabolite (n = 4/4) identified in conjugated form in serum [tandem mass spectrometry (MS/MS)] and urine [gas chromatography (GC) MS]. Serum acylcarnitines and urine organic acid profiles (n = 7) were determined for SPM horses.
  
  
  RESULTS
  Seeds from box elder trees (Acer negundo) were present on all SPM and 61% of control pastures. Hypoglycin A, known to cause acquired multiple acyl-CoA dehydrogenase deficiency (MADD), was found in box elder seeds. Serum acylcarnitines and urine organic acid profiles in SPM horses were typical for MADD. The hypoglycin A metabolite methylenecyclopropylacetic acid (MCPA), known to be toxic in other species, was found in conjugated form in SPM horse serum and urine. Horses with SPM had longer turn-out, more overgrazed pastures, and less supplemental feeding than control horses.
  
  
  CONCLUSIONS
  For the first time, SPM has been linked to a toxin in seeds abundant on autumn pastures whose identified metabolite, MCPA, is known to cause acquired MADD, the pathological mechanism behind SPM and AM. Further research is required to determine the lethal dose of hypoglycin A in horses, as well as factors that affect annual seed burden and hypoglycin A content in Acer species in North America and Europe.
authors.affiliation: Department of Veterinary Population Medicine, College of Veterinary Medicine, University of Minnesota, St Paul, Minnesota, USA. valbe001@umn.edu
authors.forename: S J
authors.initials: SJ
authors.lastname: Valberg
authors.forename: B T
authors.initials: BT
authors.lastname: Sponseller
authors.forename: A D
authors.initials: AD
authors.lastname: Hegeman
authors.forename: J
authors.initials: J
authors.lastname: Earing
authors.forename: J B
authors.initials: JB
authors.lastname: Bender
authors.forename: K L
authors.initials: KL
authors.lastname: Martinson
authors.forename: S E
authors.initials: SE
authors.lastname: Patterson
authors.forename: L
authors.initials: L
authors.lastname: Sweetman
mesh_terms: D031002:Acer / Q000737:chemistry*; D000818:Animals; D016022:Case-Control Studies; D003521:Cyclopropanes / Q000737:chemistry / Q000652:urine; D003625:Data Collection; D005260:Female; D007005:Hypoglycins / Q000097:blood / Q000633:toxicity* / Q000652:urine; D007484:Iowa / Q000453:epidemiology; D008297:Male; D008910:Minnesota / Q000453:epidemiology; D009135:Muscular Diseases / Q000139:chemically induced / Q000662:veterinary*; D010939:Plant Poisoning / Q000662:veterinary*; D012621:Seasons; D012639:Seeds / Q000737:chemistry*; D011795:Surveys and Questionnaires; D014922:Wisconsin / Q000453:epidemiology
chemical_list: D003521:Cyclopropanes; D007005:Hypoglycins; C041757:hypoglycin; C013122:methylenecyclopropylacetic acid