Polysaccharide Storage Myopathy: Blame It on the Genes

A genetic mutation in an enzyme called muscle glycogen synthase might be responsible for polysaccharide storage myopathy (PSSM)--a debilitating and life-threatening disease in horses characterized by abnormally high glycogen (the storage form of glucose) levels in skeletal muscles.

PSSM is currently estimated to affect more than one-third of draft horses and one-tenth of all Quarter Horses. Affected horses commonly have episodes of tying-up and muscle soreness; however, in some cases, muscle atrophy (decrease in muscle size), weakness, and gait abnormalities are present. In severe cases, horses with PSSM might be unable to rise after lying down.

"Over one hundred years ago this disease was called Monday Morning Disease and its cause was unclear," explained Stephanie Valberg, DVM, PhD, Dipl. ACVIM, from the Department of Veterinary Population Medicine at the University of Minnesota. "We are thrilled to have uncovered its genetic cause after 20 years of searching."

Muscle biopsy of a horse with PSSM

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

The discovery was part of Molly McCue's (DVM, MS, PhD, Dipl. ACVIM) PhD dissertation. McCue's research was conducted in the laboratory run by Jim Mickelson MS, PhD, in Minnesota.

In this study, McCue and colleagues analyzed the DNA from 48 Quarter Horses with PSSM and another 48 Quarter Horses that were PSSM-free.

"Our results identified a genetic mutation in the group of horses with PSSM," said McCue. "In the gene for the enzyme called glycogen synthase, a single mutation resulted in an overactive enzyme."

According to McCue, "This research is not only exciting for the equine world, but also for medicine in general. Mutations that result in an increase in enzyme function are rare."

This mutation results in an increase in glycogen synthesis in the muscle tissue of affected horses and a disruption in normal energy metabolism. Research to further understand the exact metabolic steps in PSSM that cause muscle damage and exertional rhabdomyolysis (tying up) are ongoing.

The study, "Glycogen synthase (GYS1) mutation causes a novel skeletal muscle glycogenosis" is scheduled to be published in an upcoming edition of the journal Genome. Contributing authors were McCue; Valberg; Miller; Wade; DiMauro; Akman, and; Mickelson.

For more on PSSM research see New Research on PSSM Prevalence, Heritability in Progress.

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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