Severe Inhibition of Long-Chain Acyl-CoA Enoylhydratase (EC 4.2.1.74) in a Newborn Foal Suffering From Atypical Myopathy.
Authors: Sander Johannes, Terhardt Michael, Janzen Nils
Journal: Frontiers in veterinary science
Summary
# Editorial Summary Atypical myopathy in horses typically results from exposure to hypoglycin A and methylenecyclopropylglycine—toxins produced by sycamore and maple species—yet most foals exposed in utero or through colostrum remain clinically healthy, suggesting an additional genetic or metabolic predisposition is required for disease manifestation. Johannes and colleagues investigated a symptomatic newborn foal using advanced tandem mass spectrometry to quantify maple toxins, their metabolites, and the full spectrum of acylcarnitines, comparing findings against both affected horses and unmedicated controls. Whilst the foal's serum contained only low concentrations of hypoglycin A and toxin metabolites well below those documented in clinically affected animals, the researchers identified a striking accumulation of long-chain acylcarnitines (tetradecenoylcarnitine and hexadecenoylcarnitine), indicating specific inhibition of long-chain enoyl-CoA hydratase (EC 4.2.1.74)—a critical enzyme in fatty acid β-oxidation not previously reported as isolated dysfunctional in any species. This finding reveals that vertical transmission of maple toxins alone is insufficient to cause disease; rather, an underlying genetic susceptibility affecting long-chain fatty acid metabolism appears necessary, fundamentally altering how we should consider the interplay between toxin exposure and individual metabolic vulnerability in neonatal atypical myopathy. Practitioners should recognise that genetic screening and family histories may become clinically relevant for identifying at-risk foals in affected yards, whilst further research is urgently needed to characterise this previously undescribed enzymatic defect.
Read the full abstract on PubMed
Practical Takeaways
- •Not all foals exposed to maple toxins in utero or via colostrum will develop atypical myopathy; individual genetic factors and specific enzyme sensitivities determine clinical outcome—genetic screening may help identify at-risk animals.
- •If a newborn foal shows atypical myopathy signs with atypical biochemical markers despite known dam exposure to maple species, consider investigating for rare metabolic enzyme defects beyond standard toxin quantification.
- •This case highlights that vertical transmission of environmental toxins combined with specific genetic predispositions can create rare but severe clinical presentations; thorough investigation of unusual cases may reveal previously unrecognized genetic diseases.
Key Findings
- •A newborn foal developed atypical myopathy despite low serum hypoglycin A levels and toxin metabolites <3.5% of clinically affected horses, suggesting genetic predisposition was necessary for disease manifestation.
- •Markedly elevated tetradecenoylcarnitine and hexadecenoylcarnitine in foal serum indicated specific blockade of long-chain enoyl-CoA hydratase (EC 4.2.1.74), an enzyme dysfunction not previously reported in any species.
- •Vertical transmission of maple toxins from dam to foal via placenta/colostrum combined with a specific genetic reactivity to toxins was sufficient to induce clinical disease in this case.
- •Long-chain acylcarnitine abnormalities, rather than short/medium-chain patterns typical of uncomplicated acer poisoning, were the distinguishing biochemical feature of this case.