Equis ISSN 2398-2977

Muscle: myopathy - atypical

Synonym(s): Seasonal pasture myopathy, SPM, Hypoglycin-associated myopathy, Atypical myopathy, Rhabdomyolysis, Sycamore poisoning

Contributor(s): Steve Adair, Anna Renier, Stephanie Valberg, Han van der Kolk, David Rendle

Introduction

  • Seasonal pasture myopathy/atypical myopathy is a highly fatal, toxic, non-exertional rhabdomyolysis that causes multiple acyl-CoA dehydrogenase deficiency (MADD).
  • Cause: ingestion of hypoglycin A. 
  • Signs: lethargy, weakness, recumbency, depression, muscle fasciculations, choke, pigmenturia, dyspnea, respiratory failure, sweating.
  • Diagnosis: clinical signs, blood biochemistry, identification of hypoglycin and acylcarnitine profiles in blood, histopathology of Type 1 muscle.
  • Treatment: supportive.
  • Prognosis: poor.
Print off the Owner factsheet on Seasonal pasture myopathy - atypical myopathy to give to your client.

Pathogenesis

Etiology

  • Ingestion of hypoglycin A contained in samaras (fruit), seeds and/or seedlings from the common (European) sycamore maple tree (Acer pseudoplatanus) and box elder (Acer negundo) which results in a lipid storage myopathy. Year old sycamore saplings have also been found to still test positive for hypoglycin A. 
  • Rainwater that has come in contact with sycamore seedlings may also contain hypoglycin A.
  • The toxic dose appears to vary markedly between horses and the concentration of toxin is highly variable between seeds. Estimates of the number of seeds that need to be ingested to cause disease varies from dozens to thousands.
  • One study found that during some periods <20 g of samaras (approximately 50 seedlings) are enough to reach toxic levels. It also suggested that this dose may also be reached by ingesting 150 g of inflorescencs or 2 l of in-contact rainwater.
  • Outbreaks are common and occurrence is seasonal.

Predisposing factors

General

Environmental

  • Presence of seed-bearing trees: factors which determine individual seed toxicity are unknown at this time, but may be related to climate.
  • >90% of cases are seen most commonly in fall/autumn months, although occasional cases occur after first frosts/snow.
  • A smaller rise in cases occurs in the spring in association with the emergence of seedlings.
  • Inclement weather: heavy wind and rain often occur in the week preceding clinical cases; such weather likely increases seed dispersion.
  • Sparse pasture and absence of supplemental forage; presumably because horses are more likely to ingest seeds.
  • Introduction of new horses to a pasture containing these trees, especially during high risk periods: horses that have recently moved to a new farm or pasture may be at increased risk for SPM/AM; may be higher risk in younger animals.

Horse

  • Young horses are more likely to be affected; the disease has not been reported in foals.
  • Pasture turnout >6 h/day.
  • Horses that are not in work are at greater risk, probably because they are more likely to have extended access to pasture.

Pathophysiology

  • Upon ingestion, hypoglycin A is metabolized to methylenecyclopropylacetic acid (MCPA) which is then converted to MCPA-CoA.
  • Short, medium and long-chain acyl-CoA dehydrogenases serve to convert their respective length fatty acyl-CoAs into acetyl-CoA for the citric acid cycle, releasing NADH and FADH2 for the electron transport chain in the process.
  • MCPA-CoA serves as a substrate for and irreversibly inhibits short and medium chain acyl-CoA dehydrogenases essential for ß-oxidation of fatty acids.
  • In addition, through sequestration of CpA and carnitine, MCPA also inhibits the carnitine-acyl-CoA transferase system required for transportation of long chain fatty acids into the mitochondria, impairing mitochondrial ß-oxidation of long chain fatty acids.
  • Amino acid metabolism (isovaleryl-, glutaryl-CoA dehydrogenases) is disrupted by MCPA through modification of the flavin adenine dinucleotide cofactor.
  • In sum, this results in an accumulation of acyl-CoAs that cannot be used for the citric acid cycle. These acyl-CoAs are transported into the blood stream as acylcarnitines, undergo alternate É oxidation and subsequently pass into the urine for elimination as acylglycines and other urine organic acids.
  • The inability of the body to utilize its acyl-CoAs from lipids results in a negative energy balance and lipid storage myopathy that precludes normal myocyte functions, resulting in cell death.
  • This category of metabolic derangements is known as Multiple Acyl-CoA Dehydrogenase Deficiency (MADD), which is also known in humans as glutaric acidemia type II.

Timecourse

  • A latent period of up to 4 days has been reported.
  • Some affected horses appear to become quiet and lethargic for a few days prior to the onset of more severe clinical signs.
  • Clinical signs tend to progress over a few days.
  • Horses that survive 3-5 days are more likely to recover.
  • Recovery from acute disease is reported to take 10.6 +/- 5.6 days, but in some cases may take considerably longer.
  • Horses that recover make a complete recovery and will return to their previous athletic potential.

Diagnosis

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Treatment

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Prevention

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Outcomes

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Further Reading

Publications

Refereed papers

  • Recent references from PubMed and VetMedResource.
  • Votion D M et al (2019) Potential new sources of hypoglycin A poisoning for equids kept at pasture in spring: a field pilot study. Vet Rec 184 (24), 740 PubMed.
  • Żuraw A, Dietert K, Kühnel S et al (2016) Equine atypical myopathy caused by hypoglycin A intoxication associated with ingestion of sycamore maple tree seeds. Equine Vet J  48 (4), 418-421 PubMed.
  • Baise E et al (2015) Samaras and seedlings of Acer pseudoplatanus are potential sources of hypoglycin A intoxication in atypical myopathy without necessarily inducing clinical signs. Equine Vet J 48 (4), 414-417 PubMed.
  • Bochnia M et al (2015) Hypoglycin a content in blood and urine discriminates horses with atypical myopathy from clinically normal horses grazing on the same pasture. PLoS ONE 10 (9), e0136785 PubMed.
  • Gröndahl G, Berglund A, Skidell J et al (2015) Clinical Research Abstracts of the British Equine Veterinary Association Congress 2015. Equine Vet J 47 Suppl 48, 22 PubMed.
  • Naylor R (2014) Managing muscle disease is horses. In Pract 36 (8), 418-423 BMJ.
  • Unger L et al (2014) Hypoglycin A concentrations in seeds of Acer pseudoplatanus trees growing on atypical myopathy-affected and control pastures. J Vet Intern Med 28 (4), 1289–1293 PubMed.
  • Valberg S J (2013) 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 PubMed.
  • VanGalenG & Votion D M (2013) Management of cases suffering from atypical myopathy: Interpretations of descriptive, epidemiological and pathophysiological findings. Part 2: Muscular, urinary, respiratory and hepatic care, and inflammatory/infectious status. Equine Vet Educ 25 (6), 308-314 VetMedResource.
  • Votion D M et al (2014) Identification of methylenecyclopropyl acetic acid in serum of European horses with atypical myopathy. Equine Vet J 46 (2), 146-149 PubMed.
  • Sponseller B T et al (2012) Equine Multiple Acyl-CoA Dehydrogenase Deficiency (MADD) Associated with Seasonal Pasture Myopathy in the Midwestern United States. J Vet Intern Med 26 (4), 1012-1018 PubMed.
  • Valberg S J et al (2012) Seasonal Pature Myopathy/Atypical Myopathy in North America associated with Ingestion of Hypoglycin A within Seeds of the Box Elder Tree. Equine Vet J [Epud ahead of print] PubMed.
  • Van Galen G et al (2012) European outbreaks of atypical myopathy in grazing equids (2006-2009): Spatiotemporal distribution, history and clinical features. Equine Vet J 44 (5), 614-620 PubMed
  • Van Galen G et al (2012) European outbreaks of atypical myopathy in grazing horses (2006-2009): Determination of indicators for risk and prognostic factors. Equine Vet J 44 (5), 621-625 PubMed.
  • Chen W P, Yang X Y, Hegeman A D et al (2010) Microscale analysis of amino acids using gas chromatography-mass spectrometry after methyl chloroformate derivatization. J Chromatogr B Analyt Technol Biomed Life Sci 878 (24), 2199-2208 PubMed.
  • Unger-Torroledo L et al (2010) Lethal toxin of Clostridium sordelli is associated with fatal equine atypical myopathy. Vet Microbiol 144 (3-4), 487-492 PubMed.
  • Van Galen G et al (2010) European outbreak of atypical myopathy in the autumn 2009. J Vet Emerg Crit Care 20 (5), 528-532 PubMed.
  • Van der Kolk J H et al (2010) Equine acquired multiple acyl-CoA dehydrogenase deficiency (MADD) in 14 horses associated with ingestion of Maple leaves (Acer pseudoplatanus) covered with European tar spot (Rhytisma acerinum). Mol Gen and Metab 101 (2-3), 289-291 PubMed.
  • Van Galen G, Serteyn D, Amory H & Votion D M (2008) Atypical myopathy: New insights into the pathophysiology, prevention and management of the condition. Equine Vet Educ 20 (5), 234-238 VetMedResource.
  • Votion D M & Serteyn D (2008) Equine atypical myopathy: A review. Vet J 178 (2), 185-190 PubMed.
  • Westermann C M et al (2008) Acquired multiple Acyl-CoA dehydrogenase deficiency in 10 horses with atypical myopathy. Neuromuscul Disord 18 (5), 355-364 PubMed.
  • Cassart D et al (2007) Morphological alterations in oxidative muscles and mitochondrial structure associated with equine atypical myopathy. Equine Vet J 39 (1), 26-32 PubMed.
  • Votion D M et al (2007) History and clinical features of atypical myopathy in horses in Belgium (2000-2005). J Vet Intern Med 21 (6), 1380-1391 PubMed.
  • Finno C J, Valberg S J, Wunschmann A & Murphy M J (2006) Seasonal pasture myopathy in horses in the Midwestern United States: 14 cases (1998-2005). JAVMA 229 (7), 1134-1141 PubMed.
  • Joskow R, Belson M, Vesper H et al (2006) Ackee fruit poisoning: an outbreak investigation in Haiti 2000-2001 and review of the literature. Clin Toxicol (Phila) 44 (3), 267-273 PubMed.
  • Salaun J (2000) Cyclopropane derivatives and their diverse biological activities. Topics Current Chem 207, 1-67 Springer.
  • Meda H A et al (1999) Epidemic of fatal encephalopathy in preschool children in Burkina Faso and consumption of unripe ackee (Blighia sapida) fruit. Lancet 353 (9152), 536-540 PubMed.
  • Rashed M S et al (1997)Screening blood spots for inborn errors of metabolism by electrospray tandem mass spectrometry with a microplate batch process and a computer algorithm for automated flagging of abnormal profiles. Clin Chem 43 (7), 1129-1141 PubMed.
  • Ikeda Y & Tanaka K (1990) Selective inactivation of various acyl-CoA dehydrogenases by (methylenecyclopropyl)acetyl-CoA. Biochem Biophys Acta 1038 (2), 216-221 PubMed.
  • Gregersen N (1985) The acyl-CoA dehydrogenation deficiencies. Recent advances in the enzymic characterization and understanding of the metabolic and pathophysiological disturbances in patients with acyl-CoA dehydrogenation deficiencies. Scand J Clin Lab Invest Suppl 174, 1-60 PubMed.
  • Wenz A, Thorpe C & Ghisla S (1981) Inactivation of general acyl-CoA dehydrogenase from pig kidney by a metabolite of hyopglycin A. J Biol Chem 256 (19), 9809-9812 PubMed.
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Other sources of information

  • Medrzycki P (2011) NOBANIS Invasive Alien species Fact Sheet Acer negundo. In: Online Database of the European Network on Invasive Alien Species. Website: www.nobanis.org. Last accessed 11th February 2013.
  • Barceloux D G (2008) Ed. Ackee fruit and Jamaican Vomiting Sickness (Blighia sapida KÖenig). In: Medical Toxicology of Natural Substances:  Foods, Fungi, Medicinal Herbs, Toxic Plants, and Venomous Animals. John Wiley & Sons, NJ. pp 34-38.
  • Frerman F E & Goodman S I (2001) Defects of Electron Transfer Flavoprotein and Electron Transfer Flavoprotein Ubiquinone Oxidoreductase: Glutaric Acidemia Type II. In: The Metabolic and Molecular Bases of Inherited diseases. Eds: Scriver C R, Beaudet A L, Sly W S & Valle D. McGraw-Hill, USA. pp 2357-2365.
  • Sweetman L (1991) Organic Acid Analysis. In: Techniques in Diagnostic Human Biochemical Genetics: A Laboratory Manual. Ed: Hommes F A. WileyLiss Inc, USA. pp 143-176.
  • Kean E R (1989) Hypoglycin. In: Toxicants of Plant Origin. Ed: Cheeke P R. CRC Press, Boca Raton, USA. pp 229-262.
  • Seasonal Pature Myopathy. Breakthrough Discovery Affecting Pastured Horses. University of Minnesota Equine Center. Website: www.cvm.umn.edu/umec/SPM/home.html. Last accessed 11th February 2013.


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