Clarifying the role of maples in atypical myopathy

Abstract

Recently, Stephanie Valberg and colleagues identified ingestion of Acer negundo (box elder) seeds as a probable cause of seasonal pasture myopathy in the USA [1]. Other recent work by Votion, Valberg and colleagues [2] and included in this issue of Equine Veterinary Journal has demonstrated that atypical myopathy in Europe is likely to have the same causal factor.The chemical in maple seeds suspected to cause these myopathies, known as hypoglycin A (2S-2-amino-3-(2-methylidenecyclopropyl)-propanoic acid), is a nonproteinogenic amino acid, which, following ingestion and metabolic activation, becomes a potent inhibitor of acyl-CoA dehydrogenase, a key enzyme active in fatty acid metabolism.At present it is not entirely clear what the risk factors for the occurrence of either form of myopathy are, as they pertain to the presence of different maple species in areas where horses reside. There are many more questions than there are answers. This editorial aims to summarise the current state of knowledge regarding plants that may play a role in this disease and suggest areas that need further study.Maples are classified within the family Sapindaceae, known as the soapberry family, along with a number of other plants, such as horse chestnut (Aesculus species) and lychee (Litchi chinensis). Ackee (Blighia sapida), the national fruit of Jamaica, is a member of this family that contains hypoglycin A in its fruit. Hypoglycin A varies in concentration in ackee fruits based on maturity, with unripe fruits containing a larger quantity of this toxin and ripe fruits a much smaller concentration [3]. When unripe fruit is ingested by humans, it may result in a disease known as Jamaican vomiting sickness, which in severe cases leads to death.Jordan and Burrows [4] were the first to report a water-soluble toxin in the seeds and pods of ackee fruit. In 1954, this toxin was isolated and 2 amino acids identified by Hassall et al. [5], who named them hypoglycin A and hypoglycin B because of their hypoglycaemic activity. In 1958, Feng and Patrick [6] described the effect of hypoglycin A on animals, noting that it caused 'drowsiness progressing to coma, and when large doses were given the animals died'. Besides ackee fruit, and now maple seed, we are not aware of any literature implicating any other plants contributing to hypoglycin A poisoning in mammals, though related compounds have been observed in other genera of Sapindaceae (including 2-amino-4-methylhex-4-enoic acid in Aesculus californica [California buckeye], and hypoglycin B, the γ-glutamyl dipeptide of hypoglycin A, in Billia hippocastanum).Currently, there is very little information on the concentration of hypoglycin A in the seeds of various maples. One of the authors of this article (A.D.H.) has quantified hypoglycin A in 2 maple species, namely Acer negundo (box elder) and Acer pseudoplatanus (sycamore maple; A. D. Hegeman, unpublished results). This is consistent with work by Fowden and Pratt [7], who provided a qualitative description of a strong hypoglycin A response in ...

Hypoglycin A Concentrations in Maple Tree Species in the Netherlands and the Occurrence of Atypical Myopathy in Horses

“…However, whether horses eat seeds or sprouts is to a large extent determined by the availability of other feedstuff . In general, Spring pasture contains more and better grass than Autumn pasture, and thus horses may have less reason to eat other feedstuff …”

“…Owners should be advised to mow areas of pasture with Maple sprouts and to remove the mown material. A factor that needs further investigation is tree stress . Tree stress or abiotic stress may increase the hypoglycin A concentration in seeds.…”

“…Because sprouts are more common in Spring and seeds are more common in Autumn, it would appear that horses eat more seeds than sprouts either because more seeds are available or because they prefer seeds to sprouts. However, whether horses eat seeds or sprouts is to a large extent determined by the availability of other feedstuff . In general, Spring pasture contains more and better grass than Autumn pasture, and thus horses may have less reason to eat other feedstuff …”

Intoxication of the immature fruit of the ackee (Blighia sapida Koenig): Summary and development

“…At liver biopsy, central lobular necrosis is observed [23]. A typical equine myopathy, a relatively rare disease touching horses consuming the seeds or seedlings of some maples, is known to be caused by hypoglycin A [21].…”

“…The correction of hypoglycemia is the first emergency of this therapy. It is done by the infusion of glucose serum (SG): 1cc/kg of SG 30% or 3 to 5cc/kg of SG 10% [7,21,[24][25][26][27][28]. Glucagon can be used from 0.5 to 1 mg intramuscularly or subcutaneously.…”