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Equine veterinary journal2012; 45(4); 419-426; doi: 10.1111/j.2042-3306.2012.00684.x

Seasonal pasture myopathy/atypical myopathy in North America associated with ingestion of hypoglycin A within seeds of the box elder tree.

Abstract: 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.
Publication Date: 2012-11-20 PubMed ID: 23167695DOI: 10.1111/j.2042-3306.2012.00684.xGoogle Scholar: Lookup
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  • Journal Article
  • Research Support
  • Non-U.S. Gov't

Summary

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The research article presents a study that links the seasonal pasture myopathy (SPM), a horse disease, to the intake of hypoglycin A from the seeds of box elder trees, which becomes abundant during autumn. The toxic action of this amino acid seems to operate via a mechanism known as acquired multiple acyl-CoA dehydrogenase deficiency (MADD).

Objective and Methodology

The researchers aimed to identify a seed-bearing plant common in the autumn pastures of horses showing signs of seasonal pasture myopathy (SPM), which heavily mirrors the symptoms of atypical myopathy (AM). They also sought to confirm whether the SPM condition was the result of consuming the toxic amino acid hypoglycin A found in these plants.

  • Twelve instances of SPM were studied with additional visits to 11 SPM pastures and 23 control farms. The purpose was to find a plant common to all these locations during the autumn season.
  • A widely occurring seed from these visits was tested for its amino acid profile using gas chromatography-mass spectrometry (GC-MS) to check for the presence of hypoglycin A.
  • The serum and urine samples from the horses were also examined, looking for the metabolite of hypoglycin A, specifically in its conjugated form.
  • The researchers also explored the serum acylcarnitines and urine organic acid profiles of SPM-affected horses.

Results

  • The researchers identified seeds from box elder trees (Acer negundo) in all SPM and 61% of control pastures.
  • Hypoglycin A, known to cause MADD disorder, was discovered in box elder seeds. Thus, the ingestion of these seeds by horses potentially linked the cause of SPM and AM to this specific amino acid.
  • The serum acylcarnitines and urine organic acid profiles in SPM horses were found to be typical to instances of MADD, reinforcing the link.
  • The metabolite of hypoglycin A, 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 common conditions such as longer turn-out, overgrazed pastures, and less supplemental feeding compared to control horses.

Conclusions

The research, for the first time, links the condition of SPM to a toxin (hypoglycin A) in box elder seeds abundant in autumn pastures. The findings may serve as a critical ground for future research aimed at determining the lethal dose of hypoglycin A in horses, as well as the factors influencing the annual seed burden and hypoglycin A levels in Acer species across North America and Europe.

Cite This Article

APA
Valberg SJ, Sponseller BT, Hegeman AD, Earing J, Bender JB, Martinson KL, Patterson SE, Sweetman L. (2012). Seasonal pasture myopathy/atypical myopathy in North America associated with ingestion of hypoglycin A within seeds of the box elder tree. Equine Vet J, 45(4), 419-426. https://doi.org/10.1111/j.2042-3306.2012.00684.x

Publication

ISSN: 2042-3306
NlmUniqueID: 0173320
Country: United States
Language: English
Volume: 45
Issue: 4
Pages: 419-426

Researcher Affiliations

Valberg, S J
  • Department of Veterinary Population Medicine, College of Veterinary Medicine, University of Minnesota, St Paul, Minnesota, USA. valbe001@umn.edu
Sponseller, B T
    Hegeman, A D
      Earing, J
        Bender, J B
          Martinson, K L
            Patterson, S E
              Sweetman, L

                MeSH Terms

                • Acer / chemistry
                • Animals
                • Case-Control Studies
                • Cyclopropanes / chemistry
                • Cyclopropanes / urine
                • Data Collection
                • Female
                • Hypoglycins / blood
                • Hypoglycins / toxicity
                • Hypoglycins / urine
                • Iowa / epidemiology
                • Male
                • Minnesota / epidemiology
                • Muscular Diseases / chemically induced
                • Muscular Diseases / veterinary
                • Plant Poisoning / veterinary
                • Seasons
                • Seeds / chemistry
                • Surveys and Questionnaires
                • Wisconsin / epidemiology

                Citations

                This article has been cited 35 times.
                1. François AC, Taminiau B, Renaud B, Gonza-Quito IE, Massey C, Hyde C, Piercy RJ, Douny C, Scippo ML, Daube G, Gustin P, Delcenserie V, Votion DM. In Vitro Investigation of Equine Gut Microbiota Alterations During Hypoglycin A Exposure. Animals (Basel) 2025 Nov 19;15(22).
                  doi: 10.3390/ani15223343pubmed: 41302050google scholar: lookup
                2. Bauquier J, Takahashi C, Rosales C, Pitt J. Suspected marsh mallow (Malva parviflora) toxicosis in ponies-Case cluster including an asymptomatic survivor. Aust Vet J 2025 Oct;103(10):688-692.
                  doi: 10.1111/avj.13455pubmed: 40506390google scholar: lookup
                3. François AC, Cesarini C, Taminiau B, Renaud B, Kruse CJ, Boemer F, van Loon G, Palmers K, Daube G, Wouters CP, Lecoq L, Gustin P, Votion DM. Unravelling Faecal Microbiota Variations in Equine Atypical Myopathy: Correlation with Blood Markers and Contribution of Microbiome. Animals (Basel) 2025 Jan 26;15(3).
                  doi: 10.3390/ani15030354pubmed: 39943124google scholar: lookup
                4. González-Medina S, Hyde C, Chang YM, Piercy RJ. Assessment of tree-associated atypical myopathy risk factors in Acer pseudoplatanus (sycamore) seeds and leaves. Equine Vet J 2025 Nov;57(6):1656-1665.
                  doi: 10.1111/evj.14475pubmed: 39865342google scholar: lookup
                5. Wouters CP, Klein B, Price N, Boemer F, Voz ML, Votion DM. A Zebrafish Embryo Model to Screen Potential Therapeutic Compounds in Sapindaceae Poisoning. Molecules 2024 Oct 19;29(20).
                  doi: 10.3390/molecules29204954pubmed: 39459322google scholar: lookup
                6. Kruse CJ, Dieu M, Renaud B, François AC, Stern D, Demazy C, Burteau S, Boemer F, Art T, Renard P, Votion DM. New Pathophysiological Insights from Serum Proteome Profiling in Equine Atypical Myopathy. ACS Omega 2024 Feb 13;9(6):6505-6526.
                  doi: 10.1021/acsomega.3c06647pubmed: 38371826google scholar: lookup
                7. Aboling S. Do Poisonous Plants in Pastures Communicate Their Toxicity? Meta-Study and Evaluation of Poisoning Cases in Central Europe. Animals (Basel) 2023 Dec 8;13(24).
                  doi: 10.3390/ani13243795pubmed: 38136831google scholar: lookup
                8. Engel AM, El-Khatib AH, Klevenhusen F, Weiss M, Aboling S, Sachse B, Schäfer B, Weigel S, Pieper R, Fischer-Tenhagen C. Detection of Hypoglycin A and MCPrG Metabolites in the Milk and Urine of Pasture Dairy Cows after Intake of Sycamore Seedlings. J Agric Food Chem 2023 Jul 19;71(28):10751-10760.
                  doi: 10.1021/acs.jafc.3c01248pubmed: 37419492google scholar: lookup
                9. El-Khatib AH, Lamp J, Weigel S. A sensitive LC-MS/MS method for the quantification of the plant toxins hypoglycin A and methylenecyclopropylglycine and their metabolites in cow's milk and urine and application to farm milk samples from Germany. Anal Bioanal Chem 2023 Apr;415(10):1933-1942.
                  doi: 10.1007/s00216-023-04607-9pubmed: 36877265google scholar: lookup
                10. El-Khatib AH, Engel AM, Weigel S. Co-Occurrence of Hypoglycin A and Hypoglycin B in Sycamore and Box Elder Maple Proved by LC-MS/MS and LC-HR-MS. Toxins (Basel) 2022 Sep 1;14(9).
                  doi: 10.3390/toxins14090608pubmed: 36136546google scholar: lookup
                11. Jahn P, Dobešová D, Brumarová R, Tóthová K, Kopecká A, Friedecký D. Dynamics of acylcarnitines, hypoglycin A, méthylènecyclopropylglycine and their metabolites in a Kladruber stallion with atypical myopathy. Vet Q 2022 Dec;42(1):183-191.
                  doi: 10.1080/01652176.2022.2126537pubmed: 36114619google scholar: lookup
                12. Renaud B, Kruse CJ, François AC, Grund L, Bunert C, Brisson L, Boemer F, Gault G, Ghislain B, Petitjean T, Gustin P, Votion DM. Acer pseudoplatanus: A Potential Risk of Poisoning for Several Herbivore Species. Toxins (Basel) 2022 Jul 26;14(8).
                  doi: 10.3390/toxins14080512pubmed: 35893754google scholar: lookup
                13. Mathis D, Sass JO, Graubner C, Schoster A. Diagnosis of atypical myopathy based on organic acid and acylcarnitine profiles and evolution of biomarkers in surviving horses. Mol Genet Metab Rep 2021 Dec;29:100827.
                  doi: 10.1016/j.ymgmr.2021.100827pubmed: 34900597google scholar: lookup
                14. Kruse CJ, Stern D, Mouithys-Mickalad A, Niesten A, Art T, Lemieux H, Votion DM. In Vitro Assays for the Assessment of Impaired Mitochondrial Bioenergetics in Equine Atypical Myopathy. Life (Basel) 2021 Jul 20;11(7).
                  doi: 10.3390/life11070719pubmed: 34357091google scholar: lookup
                15. Bochnia M, Ziegler J, Glatter M, Zeyner A. Hypoglycin A in Cow's Milk-A Pilot Study. Toxins (Basel) 2021 May 26;13(6).
                  doi: 10.3390/toxins13060381pubmed: 34073628google scholar: lookup
                16. González-Medina S, Bevin W, Alzola-Domingo R, Chang YM, Piercy RJ. Hypoglycin A absorption in sheep without concurrent clinical or biochemical evidence of disease. J Vet Intern Med 2021 Mar;35(2):1170-1176.
                  doi: 10.1111/jvim.16077pubmed: 33675130google scholar: lookup
                17. Renaud B, François AC, Boemer F, Kruse C, Stern D, Piot A, Petitjean T, Gustin P, Votion DM. Grazing Mares on Pasture with Sycamore Maples: A Potential Threat to Suckling Foals and Food Safety through Milk Contamination. Animals (Basel) 2021 Jan 5;11(1).
                  doi: 10.3390/ani11010087pubmed: 33466424google scholar: lookup
                18. Bochnia M, Ziemssen E, Sander J, Stief B, Zeyner A. Methylenecyclopropylglycine and hypoglycin A intoxication in three Pére David's Deers (Elaphurus davidianus) with atypical myopathy. Vet Med Sci 2021 May;7(3):998-1005.
                  doi: 10.1002/vms3.406pubmed: 33314647google scholar: lookup
                19. Votion DM, François AC, Kruse C, Renaud B, Farinelle A, Bouquieaux MC, Marcillaud-Pitel C, Gustin P. Answers to the Frequently Asked Questions Regarding Horse Feeding and Management Practices to Reduce the Risk of Atypical Myopathy. Animals (Basel) 2020 Feb 24;10(2).
                  doi: 10.3390/ani10020365pubmed: 32102384google scholar: lookup
                20. Sander J, Terhardt M, Sander S, Aboling S, Janzen N. A new method for quantifying causative and diagnostic markers of methylenecyclopropylglycine poisoning. Toxicol Rep 2019;6:803-808.
                  doi: 10.1016/j.toxrep.2019.08.002pubmed: 31440457google scholar: lookup
                21. Bochnia M, Sander J, Ziegler J, Terhardt M, Sander S, Janzen N, Cavalleri JV, Zuraw A, Wensch-Dorendorf M, Zeyner A. Detection of MCPG metabolites in horses with atypical myopathy. PLoS One 2019;14(2):e0211698.
                  doi: 10.1371/journal.pone.0211698pubmed: 30721263google scholar: lookup
                22. Karlíková R, Široká J, Mech M, Friedecký D, Janečková H, Mádrová L, Hrdinová F, Drábková Z, Dobešová O, Adam T, Jahn P. Newborn foal with atypical myopathy. J Vet Intern Med 2018 Sep;32(5):1768-1772.
                  doi: 10.1111/jvim.15236pubmed: 30216546google scholar: lookup
                23. Sanford AA, Isenberg SL, Carter MD, Mojica MA, Mathews TP, Laughlin S, Thomas JD, Pirkle JL, Johnson RC. Quantification of hypoglycin A and methylenecyclopropylglycine in human plasma by HPLC-MS/MS. J Chromatogr B Analyt Technol Biomed Life Sci 2018 Sep 15;1095:112-118.
                  doi: 10.1016/j.jchromb.2018.07.017pubmed: 30056267google scholar: lookup
                24. González Medina S, Hyde C, Lovera I, Piercy RJ. Detection of equine atypical myopathy-associated hypoglycin A in plant material: Optimisation and validation of a novel LC-MS based method without derivatisation. PLoS One 2018;13(7):e0199521.
                  doi: 10.1371/journal.pone.0199521pubmed: 29969503google scholar: lookup
                25. Pinn TL, Divers TJ, Southard T, De Bernardis NP, Wakshlag JJ, Valberg S. Persistent hypoglycemia associated with lipid storage myopathy in a paint foal. J Vet Intern Med 2018 Jul;32(4):1442-1446.
                  doi: 10.1111/jvim.15218pubmed: 29957835google scholar: lookup
                26. Bunert C, Langer S, Votion DM, Boemer F, Müller A, Ternes K, Liesegang A. Atypical myopathy in Père David's deer (Elaphurus davidianus) associated with ingestion of hypoglycin A. J Anim Sci 2018 Jul 28;96(8):3537-3547.
                  doi: 10.1093/jas/sky200pubmed: 29762728google scholar: lookup
                27. Isenberg SL, Carter MD, Hayes SR, Graham LA, Johnson D, Mathews TP, Harden LA, Takeoka GR, Thomas JD, Pirkle JL, Johnson RC. Quantification of Toxins in Soapberry (Sapindaceae) Arils: Hypoglycin A and Methylenecyclopropylglycine. J Agric Food Chem 2016 Jul 13;64(27):5607-13.
                  doi: 10.1021/acs.jafc.6b02478pubmed: 27367968google scholar: lookup
                28. Westermann CM, van Leeuwen R, van Raamsdonk LW, Mol HG. Hypoglycin A Concentrations in Maple Tree Species in the Netherlands and the Occurrence of Atypical Myopathy in Horses. J Vet Intern Med 2016 May;30(3):880-4.
                  doi: 10.1111/jvim.13927pubmed: 26995161google scholar: lookup
                29. Gomez DE, Valberg SJ, Magdesian KG, Hanna PE, Lofstedt J. Acquired multiple acyl-CoA dehydrogenase deficiency and marked selenium deficiency causing severe rhabdomyolysis in a horse. Can Vet J 2015 Nov;56(11):1166-71.
                  pubmed: 26538673
                30. Bochnia M, Ziegler J, Sander J, Uhlig A, Schaefer S, Vollstedt S, Glatter M, Abel S, Recknagel S, Schusser GF, Wensch-Dorendorf M, Zeyner A. Hypoglycin A Content in Blood and Urine Discriminates Horses with Atypical Myopathy from Clinically Normal Horses Grazing on the Same Pasture. PLoS One 2015;10(9):e0136785.
                  doi: 10.1371/journal.pone.0136785pubmed: 26378918google scholar: lookup
                31. Isenberg SL, Carter MD, Graham LA, Mathews TP, Johnson D, Thomas JD, Pirkle JL, Johnson RC. Quantification of metabolites for assessing human exposure to soapberry toxins hypoglycin A and methylenecyclopropylglycine. Chem Res Toxicol 2015 Sep 21;28(9):1753-9.
                32. Ryan RO. Metabolic annotation of 2-ethylhydracrylic acid. Clin Chim Acta 2015 Aug 25;448:91-7.
                  doi: 10.1016/j.cca.2015.06.012pubmed: 26115894google scholar: lookup
                33. Unger L, Nicholson A, Jewitt EM, Gerber V, Hegeman A, Sweetman L, Valberg S. Hypoglycin A concentrations in seeds of Acer pseudoplatanus trees growing on atypical myopathy-affected and control pastures. J Vet Intern Med 2014 Jul-Aug;28(4):1289-93.
                  doi: 10.1111/jvim.12367pubmed: 24863395google scholar: lookup
                34. Wakitani S, Torisu S, Yoshino T, Hattanda K, Yamato O, Tasaki R, Fujita H, Nishino K. Multiple Acyl-CoA Dehydrogenation Deficiency (Glutaric Aciduria Type II) with a Novel Mutation of Electron Transfer Flavoprotein-Dehydrogenase in a Cat. JIMD Rep 2014;13:43-51.
                  doi: 10.1007/8904_2013_268pubmed: 24142280google scholar: lookup
                35. Votion DM. The story of equine atypical myopathy: a review from the beginning to a possible end. ISRN Vet Sci 2012;2012:281018.
                  doi: 10.5402/2012/281018pubmed: 23762581google scholar: lookup