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Neuromuscular disorders : NMD2008; 18(5); 355-364; doi: 10.1016/j.nmd.2008.02.007

Acquired multiple Acyl-CoA dehydrogenase deficiency in 10 horses with atypical myopathy.

Abstract: The aim of the current study was to assess lipid metabolism in horses with atypical myopathy. Urine samples from 10 cases were subjected to analysis of organic acids, glycine conjugates, and acylcarnitines revealing increased mean excretion of lactic acid, ethylmalonic acid, 2-methylsuccinic acid, butyrylglycine, (iso)valerylglycine, hexanoylglycine, free carnitine, C2-, C3-, C4-, C5-, C6-, C8-, C8:1-, C10:1-, and C10:2-carnitine as compared with 15 control horses (12 healthy and three with acute myopathy due to other causes). Analysis of plasma revealed similar results for these predominantly short-chain acylcarnitines. Furthermore, measurement of dehydrogenase activities in lateral vastus muscle from one horse with atypical myopathy indeed showed deficiencies of short-chain acyl-CoA dehydrogenase (0.66 as compared with 2.27 and 2.48 in two controls), medium-chain acyl-CoA dehydrogenase (0.36 as compared with 4.31 and 4.82 in two controls) and isovaleryl-CoA dehydrogenase (0.74 as compared with 1.43 and 1.61 nmol min(-1) mg(-1) in two controls). A deficiency of several mitochondrial dehydrogenases that utilize flavin adenine dinucleotide as cofactor including the acyl-CoA dehydrogenases of fatty acid beta-oxidation, and enzymes that degrade the CoA-esters of glutaric acid, isovaleric acid, 2-methylbutyric acid, isobutyric acid, and sarcosine was suspected in 10 out of 10 cases as the possible etiology for a highly fatal and prevalent toxic equine muscle disease similar to the combined metabolic derangements seen in human multiple acyl-CoA dehydrogenase deficiency also known as glutaric acidemia type II.
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Publication Date: 2008-04-11 PubMed ID: 18406615DOI: 10.1016/j.nmd.2008.02.007Google Scholar: Lookup
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  • Journal Article

Summary

This research summary has been generated with artificial intelligence and may contain errors and omissions. Refer to the original study to confirm details provided. Submit correction.

This study explored lipid metabolism in horses afflicted with atypical myopathy, a severe muscle disease. The researchers found high excretion levels of various acids and glycines in the urine and plasma of the affected horses, pointing to a potential deficiency in mitochondrial dehydrogenases – a characteristic also observed in a similar human disease called glutaric acidemia type II.

Methods

  • This research involved examination of urine samples from 10 horses suffering from atypical myopathy. These were measured for levels of various organic acids, glycine conjugates, and acylcarnitines.
  • The horses’ results were compared with those of 15 control horses, 12 of which were healthy and three of which suffered from acute myopathy due to other causes.
  • The team also tested the plasma of the affected horses for similar markers.
  • Dehydrogenase activities in the lateral vastus muscle from one horse with atypical myopathy was measured and compared with two healthy horses.

Results

  • The affected horses demonstrated increased excretion of substances like lactic acid, ethylmalonic acid, 2-methylsuccinic acid, and various glycines and carnitines when compared to the control horses.
  • Similar results were seen in the plasma analysis for these predominantly short-chain acylcarnitines.
  • The muscle analysis revealed deficiencies in short-chain acyl-CoA dehydrogenase, medium-chain acyl-CoA dehydrogenase, and isovaleryl-CoA dehydrogenase in the affected horse versus the controls.

Conclusion

  • The team suspected that there was a deficiency in a number of mitochondrial dehydrogenases in all 10 cases studied. These are important enzymes that help to break down various acids and sarcosine. This kind of deficiency is also seen in a severe human disorder called glutaric acidemia type II.
  • The researchers propose that these metabolic irregularities could explain the high fatality rate and prevalence of atypical myopathy, a toxic equine muscle disease.

This study therefore represents an important piece of research into understanding the metabolic mechanisms behind atypical myopathy in horses, which could guide future therapeutic strategies.

Cite This Article

APA
Westermann CM, Dorland L, Votion DM, de Sain-van der Velden MG, Wijnberg ID, Wanders RJ, Spliet WG, Testerink N, Berger R, Ruiter JP, van der Kolk JH. (2008). Acquired multiple Acyl-CoA dehydrogenase deficiency in 10 horses with atypical myopathy. Neuromuscul Disord, 18(5), 355-364. https://doi.org/10.1016/j.nmd.2008.02.007

Publication

Neuromuscular disorders : NMD
ISSN: 0960-8966
NlmUniqueID: 9111470
Country: England
Language: English
Volume: 18
Issue: 5
Pages: 355-364

Researcher Affiliations

Westermann, C M
  • Department of Equine Sciences, Medicine Section, Faculty of Veterinary Medicine, Utrecht University, Yalelaan 114, 3508 TD Utrecht, The Netherlands.
Dorland, L
    Votion, D M
      de Sain-van der Velden, M G M
        Wijnberg, I D
          Wanders, R J A
            Spliet, W G M
              Testerink, N
                Berger, R
                  Ruiter, J P N
                    van der Kolk, J H

                      MeSH Terms

                      • Acyl-CoA Dehydrogenase / deficiency
                      • Acyl-CoA Dehydrogenase / metabolism
                      • Acyl-CoA Dehydrogenases / deficiency
                      • Acyl-CoA Dehydrogenases / metabolism
                      • Animals
                      • Butyric Acid / blood
                      • Butyric Acid / urine
                      • Butyryl-CoA Dehydrogenase / deficiency
                      • Butyryl-CoA Dehydrogenase / metabolism
                      • Carnitine / analogs & derivatives
                      • Carnitine / blood
                      • Carnitine / urine
                      • Chromatography, High Pressure Liquid
                      • Female
                      • Gas Chromatography-Mass Spectrometry
                      • Glutarates / blood
                      • Glutarates / urine
                      • Horse Diseases / enzymology
                      • Horse Diseases / metabolism
                      • Horse Diseases / pathology
                      • Horses
                      • Isovaleryl-CoA Dehydrogenase / deficiency
                      • Isovaleryl-CoA Dehydrogenase / metabolism
                      • Lactic Acid / blood
                      • Lactic Acid / urine
                      • Male
                      • Microscopy, Electron
                      • Microscopy, Fluorescence
                      • Muscles / pathology
                      • Muscles / ultrastructure
                      • Muscular Diseases / enzymology
                      • Muscular Diseases / metabolism
                      • Muscular Diseases / pathology
                      • Riboflavin / blood

                      Citations

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