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Equine veterinary journal2022; 55(4); 618-631; doi: 10.1111/evj.13876

Type 2 polysaccharide storage myopathy in Quarter Horses is a novel glycogen storage disease causing exertional rhabdomyolysis.

Abstract: Both type 1 (PSSM1) and type 2 polysaccharide storage myopathy (PSSM2) are characterised by aggregates of abnormal polysaccharide in skeletal muscle. Whereas the genetic basis for PSSM1 is known (R309H GYS1), the cause of PSSM2 in Quarter Horses (PSSM2-QH) is unknown and glycogen concentrations not defined. Objective: To characterise the histopathological and biochemical features of PSSM2-QH and determine if an associated monogenic variant exists in genes known to cause glycogenosis. Methods: Retrospective case control. Methods: Sixty-four PSSM2-QH, 30 PSSM1-QH and 185 control-QH were identified from a biopsy repository and clinical data, histopathology scores (0-3), glycogen concentrations and selected glycolytic enzyme activities compared. Coding sequences of 12 genes associated with muscle glycogenoses were identified from whole genome sequences and compared between seven PSSM2-QH and five control-QH. Results: Exertional rhabdomyolysis in PSSM2-QH occurred predominantly in barrel racing and working cow/roping performance types and improved with regular exercise and a low starch/fat-supplemented diet. Histopathological scores, including the amount of amylase-resistant polysaccharide (PSSM2-QH 1.4 ± 0.6, PSSM1-QH 2.1 ± 0.3, control-QH 0 ± 0, p < 0.001), and glycogen concentrations (PSSM2-QH 129 ± 62, PSSM1-QH 175 ± 9, control-QH 80 ± 27 mmol/kg, p < 0.0001) were intermediate in PSSM2-QH with significant differences among groups. In PSSM2-QH, abnormal polysaccharide had a less filamentous ultrastructure than PSSM1-QH and phosphorylase and phosphofructokinase activities were normal. Seventeen of 30 PSSM2-QH with available pedigrees descended from one of three stallions within four generations. Of the 29 predicted high or moderate impact genetic variants identified in candidate genes, none were present in only PSSM2-QH and absent in control-QH. Conclusions: Analyses of PSSM2-QH and PSSM1-QH were performed on shipped samples, controls on frozen samples. Conclusions: PSSM2-QH is a novel glycogen storage disorder that is not the result of a mutation in genes currently known to cause muscle glycogenoses in other species. Unassigned: Ambos os tipos 1 e 2 de miopatia por acúmulo de polissacarídeo (PSSM) são caracterizados por agregados de polissacarídeos anormais no músculo esquelético. Enquanto a base genética do PSSM 1 é conhecida (R309H GYS1), a causa do PSSM2 em cavalos Quarto de Milha (PSSM2-QH) é desconhecida, e a concentração de glicogênio não é definida. Objective: Identificar as características histopatológicas e bioquímicas do PSSM-QH e determinar se há uma variante monogênica em genes conhecidos por causar glicogenose. Unassigned: Caso controlado retrospectivo. Methods: 64 PSSM2-QH, 30 PSSM1-QH e 185 QH controles foram identificados em um arquivo de dados. Informação clínica, achados histológicos (escala 0-3), concentração de glicogênio e atividade enzimática de algumas enzimas glicolíticas foram comparadas. Sequências codificadas de 12 genes associados com glicogenose muscular foram identificados nas sequências genômicas completas, e comparadas entre 7 PSSM2-QH e 5 QH controles. Results: Rabdomiólise por exercício em PSSM2-QH ocorreu predominantemente em cavalos de corrida de tambor e cavalos de team roping/trabalho com gado, e melhorou com exercício regular e uma dieta com baixo amido e alta gordura. A escala histopatológica, incluindo a quantidade de polissacarídeos resistentes à amilase (PSSM2-QH 1.4 ± 0.6, PSSM1-QH 2.1 ± 0.3, controle-QH 0 ± 0, P < 0.001), e concentrações de glicogênio (PSSM2-QH 129 ± 62, PSSM1-QH 175 ± 9, controle-QH 80 ± 27 mmol/kg, P < 0.0001) foram intermediárias em PSSM2-QH com diferença significante entre grupos. Em PSSM2-QH, polissacarídeo anormal teve uma ultraestrutura menos filamentosa do que PSSM1-QH e as atividades de fosforilase e fosfofrutoquinase foram normais. Dezessete dos 30 PSSM2-QH com pedigree disponível descendiam de 1 de 3 garanhões dentro de 4 gerações. Das 29 variações genéticas preditas a terem impacto moderado ou alto como genes candidatos, nenhuma estava presente apenas em PSSM2-QH e ausente no grupo controle-QH. PRINCIPAIS LIMITAÇÕES: As análises feitas nas amostras de PSSM2-QH e PSSM1-QH foram realizadas em amostras enviadas por correio, e as amostras dos animais controles eram amostras congeladas. CONCLUSÕES: PSSM2-QH é uma nova doença por acúmulo de glicogênio que não é o resultado de uma mutação nos genes conhecidos por causarem glicogenose muscular em outras espécies.
© 2022 The Authors. Equine Veterinary Journal published by John Wiley & Sons Ltd on behalf of EVJ Ltd.
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Publication Date: 2022-09-14 PubMed ID: 36102343DOI: 10.1111/evj.13876Google Scholar: Lookup
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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 investigates a specific type of muscle disease, called type 2 polysaccharide storage myopathy (PSSM2), in Quarter Horses. It was found that PSSM2 is a new glycogen storage disorder that is not caused by a mutation in standard glycogenosis causing genes and showed distinct features in comparison to type 1 polysaccharide storage myopathy.

Research Methods

  • A case control approach was utilized, involving 64 PSSM2-QH, 30 PSSM1-QH, and 185 control-QH horses.
  • Clinical information, histopathology scores, glycogen concentrations, and particular glycolytic enzyme activities were compared across the groups.
  • The genetic sequences of 12 genes associated with muscle glycogenoses were identified from whole genome sequences and compared between seven PSSM2-QH and five control-QH.

Results

  • Exertional rhabdomyolysis, a condition characterized by muscle breakdown, was primarily observed in PSSM2-QH horses active in barrel racing and working cow/roping performance activities. This condition seemed to improve with regular exercise and a diet low in starch and supplemented with fats.
  • Both PSSM2-QH and PSSM1-QH had higher histological scores and glycogen concentrations than control-QH, indicating the presence of abnormal polysaccharides. The genetic variance of these traits was distinct between PSSM2-QH and PSSM1-QH, indicating distinct genetic factors influencing each.
  • In PSSM2-QH horses, the microscopic structure of abnormal polysaccharide was less thread-like than in PSSM1-QH horses, and activity of the enzymes phosphorylase and phosphofructokinase were normal.

Genetic Connections

  • It was observed that 17 out of 30 PSSM2-QH horses with known pedigrees descended from one of three stallions within four generations. This suggests a potential genetic predisposition for PSSM2-QH.
  • However, out of 29 high or moderate impact genetic variants identified in muscle glycogenosis associated genes, none were exclusive to PSSM2-QH horses.
  • This outcome indicates that PSSM2-QH is likely not a result of a mutation in any of the genes currently known to cause muscle glycogenoses in other species.

Limitations and Conclusion

  • The major limitation of the study was that the samples from PSSM2-QH and PSSM1-QH were shipped in while control samples were frozen. This could potentially bring bias in results.
  • The study concludes that type 2 polysaccharide storage myopathy in Quarter Horses is a new glycogen storage disorder that does not result from a mutation in genes known to cause similar disorders in other species.

Cite This Article

APA
Valberg SJ, Williams ZJ, Finno CJ, Schultz A, Velez-Irizarry D, Henry ML, Gardner K, Petersen JL. (2022). Type 2 polysaccharide storage myopathy in Quarter Horses is a novel glycogen storage disease causing exertional rhabdomyolysis. Equine Vet J, 55(4), 618-631. https://doi.org/10.1111/evj.13876

Publication

Equine veterinary journal
ISSN: 2042-3306
NlmUniqueID: 0173320
Country: United States
Language: English
Volume: 55
Issue: 4
Pages: 618-631

Researcher Affiliations

Valberg, Stephanie J
  • Large Animal Clinical Sciences, College of Veterinary Medicine, Michigan State University, East Lansing, Michigan, USA.
Williams, Zoë J
  • Large Animal Clinical Sciences, College of Veterinary Medicine, Michigan State University, East Lansing, Michigan, USA.
Finno, Carrie J
  • Department of Population Health and Reproduction, School of Veterinary Medicine, University of California-Davis, Davis, California, USA.
Schultz, Abigail
  • Large Animal Clinical Sciences, College of Veterinary Medicine, Michigan State University, East Lansing, Michigan, USA.
Velez-Irizarry, Deborah
  • Large Animal Clinical Sciences, College of Veterinary Medicine, Michigan State University, East Lansing, Michigan, USA.
Henry, Marisa L
  • Large Animal Clinical Sciences, College of Veterinary Medicine, Michigan State University, East Lansing, Michigan, USA.
Gardner, Keri
  • Large Animal Clinical Sciences, College of Veterinary Medicine, Michigan State University, East Lansing, Michigan, USA.
Petersen, Jessica L
  • Department of Animal Science, University of Nebraska-Lincoln, Lincoln, Nebraska, USA.

MeSH Terms

  • Female
  • Cattle
  • Horses
  • Animals
  • Male
  • Retrospective Studies
  • Glycogen Storage Disease / complications
  • Glycogen Storage Disease / genetics
  • Glycogen Storage Disease / veterinary
  • Muscular Diseases / genetics
  • Muscular Diseases / veterinary
  • Muscular Diseases / pathology
  • Rhabdomyolysis / genetics
  • Rhabdomyolysis / veterinary
  • Muscle, Skeletal / pathology
  • Polysaccharides
  • Glycogen
  • Horse Diseases / genetics
  • Horse Diseases / pathology
  • Cattle Diseases / pathology

Grant Funding

  • L40 TR001136 / NCATS NIH HHS
  • L40 TR001136 / NCATS NIH HHS

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Citations

This article has been cited 1 times.
  1. Batt MC, Venzor LG, Gardner K, Reith RR, Roberts KA, Herrera NJ, Fuller AM, Sullivan GA, Mulliniks JT, Spangler ML, Valberg SJ, Steffen DJ, Petersen JL. An autosomal recessive variant in PYGM causes myophosphorylase deficiency in Red Angus composite cattle. BMC Genomics 2024 Apr 27;25(1):417.
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