Diagnosis of atypical myopathy based on organic acid and acylcarnitine profiles and evolution of biomarkers in surviving horses.
Abstract: Atypical myopathy (AM), an acquired multiple acyl-CoA dehydrogenase deficiency (MADD) in horses, induce changes in mitochondrial metabolism. Only few veterinary laboratories offer diagnostic testing for this disease. Inborn and acquired MADD exist in humans, therefore determination of organic acids (OA) in urine and acylcarnitines (AC) in blood by assays available in medical laboratories can serve as AM diagnostics. The evolution of OA and AC profiles in surviving horses is unreported. Methods: AC profiles using electrospray ionization tandem mass spectrometry (ESI-MS/MS) and OA in urine using gas chromatography mass spectrometry (GC-MS) were determined in dried blot spots (DBS, n = 7) and urine samples (n = 5) of horses with AM (n = 7) at disease presentation and in longitudinal samples from 3/4 survivors and compared to DBS (n = 16) and urine samples (n = 7) from control horses using the Wilcoxon test. Results: All short- (C2-C5) and medium-chain (C6-C12) AC in blood differed significantly (p < 0.008) between horses with AM and controls, except for C5:1 (p = 0.45) and C5OH + C4DC (p = 0.06). In AM survivors the AC concentrations decreased over time but were still partially elevated after 7 days. 14/62 (23%) of OA differed significantly between horses with AM and control horses. Concentrations of ethylmalonic acid, 2-hydroxyglutaric acid and the acylglycines (butyryl-, valeryl-, and hexanoylglycine) were highly elevated in the urine of all horses with AM at the day of disease presentation. In AM survivors, concentrations of those metabolites were initially lower and decreased during remission to approach normalization after 7 days. Conclusions: OA and AC profiling by specialized human medical laboratories was used to diagnose AM in horses. Elevation of specific metabolites were still evident several days after disease presentation, allowing diagnosis via analysis of samples from convalescent animals.
© 2021 Published by Elsevier Inc.
Publication Date: 2021-11-25 PubMed ID: 34900597PubMed Central: PMC8639802DOI: 10.1016/j.ymgmr.2021.100827Google Scholar: Lookup
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- Journal Article
Summary
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The paper explores diagnosing Atypical myopathy (AM), a mitochondrial metabolic disorder seen in horses, by assessing organic acids in urine and acylcarnitines in blood. It also investigates how these markers change over time in horses that survive the disease.
Context and Objectives
- Atypical myopathy (AM) is a condition seen in horses that results in changes in mitochondrial metabolism. It is similar to both inborn and acquired multiple acyl-CoA dehydrogenase deficiency (MADD) in humans.
- Few veterinary laboratories offer specific testing for this disease. As such, medical laboratory tests developed for human MADD for organic acids (OA) in urine and acylcarnitines (AC) in blood could serve as diagnostic tools.
- This study seeks to explore the efficacy of using these diagnostic tests for horses suffering from AM and to understand how the profile of these biomarkers evolves in horses which survive the disease.
Methods
- Blood and urine samples were taken from horses with AM and compared to samples from healthy control horses.
- Organic acid profiles in urine were tested by gas chromatography mass spectrometry (GC-MS) and acylcarnitines profiles in blood were determined using electrospray ionization tandem mass spectrometry (ESI-MS/MS).
- These samples were taken at the time of disease presentation and then regularly afterward from surviving horses to study the changes over time.
Results
- All short-chain and medium-chain acylcarnitines in blood were significantly different in horses suffering from AM compared to healthy horses, except for two specific types.
- In comparison, 23% of organic acids showed significant differences between affected and healthy horses.
- At the time of disease presentation, several specific metabolites (ethylmalonic acid, 2-hydroxyglutaric acid, butyryl-, valeryl-, and hexanoylglycine) were found to be elevated in the urine of horses with AM.
- For AM survivors, these elevated concentrations decreased during the period of recovery, approaching regular levels after roughly seven days.
Conclusion
- The organic acid and acylcarnitine profiling tests traditionally used by human medical laboratories could be used to diagnose atypical myopathy in horses.
- Certain metabolite elevations were evident for several days after disease onset, allowing for disease diagnosis from samples collected from recovering animals.
Cite This Article
APA
Mathis D, Sass JO, Graubner C, Schoster A.
(2021).
Diagnosis of atypical myopathy based on organic acid and acylcarnitine profiles and evolution of biomarkers in surviving horses.
Mol Genet Metab Rep, 29, 100827.
https://doi.org/10.1016/j.ymgmr.2021.100827 Publication
Researcher Affiliations
- University Institute of Clinical Chemistry, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland.
- Department of Clinical Chemistry and Biochemistry, University Children's Hospital Zurich, Zurich, Switzerland.
- Department of Natural Sciences & Institute for Functional Gene Analytics (IFGA), Bonn-Rhein-Sieg University of Applied Sciences, Rheinbach, Germany.
- Institut Suisse de Médecine Equine, Vetsuisse Faculty, University of Berne, Länggassstrasse 124, 3012 Berne, Switzerland.
- Clinic for Equine Internal Medicine, Equine Department, Vetsuisse Faculty, University of Zurich, Winterthurerstrasse 260, 8057 Zurich, Switzerland.
Conflict of Interest Statement
The authors have no competing interest to declare.
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