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The veterinary quarterly2022; 42(1); 183-191; doi: 10.1080/01652176.2022.2126537

Dynamics of acylcarnitines, hypoglycin A, méthylènecyclopropylglycine and their metabolites in a Kladruber stallion with atypical myopathy.

Abstract: Equine atypical myopathy (AM also referred to as multiple acyl-CoA dehydrogenases deficiency [MADD]) is thought to be caused by toxins metabolized from hypoglycin A (HGA) and méthylènecyclopropylglycine (MCPrG). HGA is contained in the seeds and seedlings of the sycamore tree (Acer pseudoplatanus); MCPrG has so far only been confirmed in seeds. Among other things, these substances can disrupt the fatty acids β-oxidation pathway with the subsequent accumulation of certain acylcarnitines. The tentative diagnosis is based on anamnesis and clinical signs and can be verified by the detection of elevated creatine kinase activity, specific profile of acylcarnitines and the presence of HGA, MCPrG conjugates and/or their metabolites in peripheral blood and/or urine. Dry blood spots were collected for 15 days from a 3.5-year-old stallion which had been affected by AM and, as a control group, from twelve healthy horses. Two mass spectrometry methods were used for the analysis of 31 acylcarnitines, carnitine, HGA, MCPrG and their metabolites. HGA and six increased acylcarnitines were detected in the patient's blood throughout the monitoring period. Nine acylcarnitines were strongly correlated with HGA. Multivariate statistical analysis showed a clear separation of samples from the AM horse, where the metabolic profile tended to normalization in the later days after intoxication. Due to the longer persistence in the blood, the detection of HGA and elevated acylcarnitines profile appear to be an appropriate tool to confirm the diagnosis of AM, compared to metabolic products of HGA and MCPrG even in advanced cases.
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Publication Date: 2022-09-18 PubMed ID: 36114619PubMed Central: PMC9518284DOI: 10.1080/01652176.2022.2126537Google Scholar: Lookup
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  • Journal Article

Summary

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The research investigates the features of Atypical Myopathy (AM) in a Kladruber stallion thought to be caused by the toxins produced from hypoglycin A (HGA) and méthylènecyclopropylglycine (MCPrG). Biomarkers within blood and urine such as acylcarnitines, HGA, MCPrG, and their metabolic products were observed. The results show that these biomarkers can be used for detection and confirmation of AM.

Overview of the Research

  • The focus of the research is on equine atypical myopathy (AM), a disorder believed to be caused by toxins metabolized from two specific substances, hypoglycin A (HGA) and méthylènecyclopropylglycine (MCPrG).
  • These toxins are known to disrupt the fatty acids β-oxidation pathway, leading to accumulation of certain acylcarnitines. This disruption and irregularity serve as potential indicators of the disorder.
  • The examination was carried out on blood samples from a 3.5-year-old stallion diagnosed with AM, over a period of 15 days. In addition, twelve samples from healthy horses were used as control.

Methodology

  • Two mass spectrometry methods were employed to analyze a total of 31 acylcarnitines, carnitine, HGA, MCPrG, and their corresponding metabolic byproducts.
  • The presence of HGA and six increased acylcarnitines were monitored and verified in the patient’s blood for the duration of the testing period.
  • Statistical analysis revealed a strong correlation between nine acylcarnitines and HGA. These samples were distinct compared to those from the healthy horses, indicating clear differences in metabolic profiles.

Findings and Conclusion

  • The researchers found that the metabolic profile of the AM-affected horse trended towards normalization in the later days post-intoxication, separating its sample from the unaffected horses.
  • The lasting presence of HGA and elevated acylcarnitines in the blood suggests that these discriminant features could be used to confirm the diagnosis of AM.
  • The research suggests that this approach could be useful even in more progressed cases, offering a more reliable diagnostic tool compared to traditional methods that rely mainly on metabolic products of HGA and MCPrG.

Cite This Article

APA
Jahn P, Dobešová D, Brumarová R, Tóthová K, Kopecká A, Friedecký D. (2022). Dynamics of acylcarnitines, hypoglycin A, méthylènecyclopropylglycine and their metabolites in a Kladruber stallion with atypical myopathy. Vet Q, 42(1), 183-191. https://doi.org/10.1080/01652176.2022.2126537

Publication

The veterinary quarterly
ISSN: 1875-5941
NlmUniqueID: 7909485
Country: England
Language: English
Volume: 42
Issue: 1
Pages: 183-191

Researcher Affiliations

Jahn, Petr
  • Equine Clinic, Faculty of Veterinary Medicine, University of Veterinary Sciences, Brno, Czech Republic.
Dobešová, Dana
  • Laboratory for Inherited Metabolic Disorders, Department of Clinical Biochemistry, University Hospital Olomouc and Faculty of Medicine and Dentistry, Palacký University Olomouc, Olomouc, Czech Republic.
Brumarová, Radana
  • Laboratory for Inherited Metabolic Disorders, Department of Clinical Biochemistry, University Hospital Olomouc and Faculty of Medicine and Dentistry, Palacký University Olomouc, Olomouc, Czech Republic.
Tóthová, Katarína
  • Equine Clinic, Faculty of Veterinary Medicine, University of Veterinary Sciences, Brno, Czech Republic.
Kopecká, Andrea
  • Equine Clinic, Faculty of Veterinary Medicine, University of Veterinary Sciences, Brno, Czech Republic.
Friedecký, David
  • Laboratory for Inherited Metabolic Disorders, Department of Clinical Biochemistry, University Hospital Olomouc and Faculty of Medicine and Dentistry, Palacký University Olomouc, Olomouc, Czech Republic.

MeSH Terms

  • Acyl-CoA Dehydrogenases
  • Animals
  • Carnitine / analogs & derivatives
  • Creatine Kinase
  • Cyclopropanes
  • Fatty Acids
  • Glycine / analogs & derivatives
  • Horse Diseases / diagnosis
  • Horses
  • Hypoglycins
  • Male
  • Muscular Diseases / diagnosis
  • Muscular Diseases / veterinary

Conflict of Interest Statement

No potential conflict of interest was reported by the authors.

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