PSSM Genetic Mutation Reported in Some UK Horse Breeds

Collaborative efforts between researchers on both sides of the Atlantic have identified that a genetic mutation in enzyme glycogen synthase 1 (GYS1) is an important cause of polysaccharide storage myopathy (PSSM, a form of exertional rhabdomyolysis) in a variety of UK horse breeds including the Cob and Connemara-cross.

Muscle biopsy of a horse with PSSM

Muscle biopsy of a horse with PSSM, showing an accumulation of abnormal polysaccharide (purple stains).

"In the United States, a gain of function mutation in GYS1 was identified in various breeds of horses that results in an increased glycogen synthase activity in skeletal muscle," explained Molly McCue, DVM, MS, PhD, Dipl. ACVIM, assistant professor at the University of Minnesota. "In turn, the GYS1 mutation results in the accumulation of an abnormal type and amount of polysaccharide (a type of carbohydrate) inclusions."

To determine the international importance of PSSM, researchers also evaluated the prevalence of the GYS1 mutation in horses from the United Kingdom. DNA (genetic material) was isolated from 47 blood or muscle biopsy samples collected from horses with microscopic evidence of grade 1 or grade 2 PSSM, and horses with a history of exertional rhabdomyolysis or poor performance. They subsequently analyzed the genetic material to determine the proportion of horses with the GYS1 mutation.

"Our study found that 21% of the 47 horses with a history of exertional rhabdomyolysis or poor performance possessed the GYS1 mutation," summarized Richard Piercy, MA, VetMB, PhD, Dipl. ACVIM, MRCVS, from the Royal Veterinary College in the UK.

"In addition, the mutation was only identified in horses with microscopic evidence of grade 2 PSSM. That is, the group of horses with microscopic evidence of myopathy in combination with an abnormal type of polysaccharide in the muscle tissues," Piercy said.

The GYS1 mutation was found in 24/37 (65%) of the horses diagnosed with grade 2 PSSM.

A variety of horses were found to carry the GYS1 mutation including Quarter Horses, Appaloosas, Warmbloods, polo ponies, Thoroughbred-crosses, Connemara-crosses, and cobs.


Dr. Molly McCue discusses research into muscle disorder PSSM.
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"The GYS1 mutation is an important cause of exertional rhabdomyolysis in certain UK breeds, but is not the underlying cause in all cases of PSSM or exertional rhabdomyolysis," said Piercy. "Nonetheless, we do recommend routine genotyping in horses with exertional rhabdomyolysis in combination with muscle biopsy, particularly in certain breeds."

The study, "A glycogen synthase 1 mutation associated with equine polysaccharide storage myopathy and exertional rhabdomyolysis occurs in a variety of UK breeds," is scheduled to be published in an upcoming edition of the Equine Veterinary Journal.

Read more about previous GYS1 research.

About the Author

Stacey Oke, DVM, MSc

Stacey Oke, MSc, DVM, is a practicing veterinarian and freelance medical writer and editor. She is interested in both large and small animals, as well as complementary and alternative medicine. Since 2005, she's worked as a research consultant for nutritional supplement companies, assisted physicians and veterinarians in publishing research articles and textbooks, and written for a number of educational magazines and websites.

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