Polysaccharide Storage Myopathy (PSSM): A Genetic Diagnosis, AAEP 2008

Polysaccharide storage myopathy (PSSM) is a metabolic muscle problem found in at least 20 breeds, including Quarter Horses, Paints, Appaloosas, and drafts. An affected horse suffers bouts of exertional rhabdomyolysis (tying-up), muscle tremors, and/or gait abnormalities. At the 2008 American Association of Equine Practitioners convention, held Dec. 6-10 in San Diego, Calif., Molly E. McCue, DVM, MS PhD, Dipl. ACVIM, an assistant professor in the Department of Veterinary Population Medicine at the University of Minnesota, presented information about genetic testing for one PSSM type.


Dr. Molly McCue discusses research into muscle disorder PSSM.
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Researchers at the university discovered a gene mutation that causes unregulated glycogen formation in the muscles of horses with PSSM. This mutation is a gene called GYS1 on chromosome 10, which encodes the skeletal muscle glycogen synthase enzyme responsible for glycogen formation. Because this enzyme is constantly active in affected horses, they accumulate excess glycogen in the cells.

Did this mutation derive from a single horse? McCue explained that the "signature" of this mutation is like a bar code and can be traced back in time. It is believed to have arisen from a single horse about 144-178 horse generations ago, i.e. about 1,200-1,500 years ago. This corresponds to the "Great Horses" of war--described by medieval writers--that founded modern draft breeds.

While the phenotype (physical attributes) of affected horses varies widely, the extent of the muscle metabolic problem ranges from unrecognized subclinical disease to overt exertional rhabdomyolysis to recumbency that necessitates euthanasia.

McCue reported that approximately 8% of Quarter Horses have this GYS1 mutation. Re-evaluation of horses tested and found to have PSSM (diagnosed by muscle biopsy) indicated that about 75% of PSSM Quarter Horses and 85% of PSSM draft horses had the GYS1 mutation; a small percentage of Quarter Horses have another form of PSSM not due to the GYS1 mutation.

Also, 18 of 35 breeds were negative for the mutation, and there was a low prevalence of the GYS1 mutation in many Warmbloods diagnosed with PSSM by muscle biopsy. Therefore, many PSSM-affected Warmbloods might have another genetic mutation that causes PSSM.

The investigators found that 100% of Arabians, Thoroughbreds, and Standardbreds were affected by something other than the GYS1 mutation that causes tying-up and excessive glycogen storage.

PSSM is categorized into two different types: Type-1 PSSM defines horses with a GYS1 mutation--mostly seen in Quarter Horse, Paint, and Appaloosa purebreds or crosses, draft breeds, Morgans, and Tennessee Walking Horses. Type 2 PSSM is found in a variety of other breeds, and its cause is not yet known.

McCue also described a family of severely affected PSSM horses that do not respond well to treatment and might suffer acute death following an episode of tying-up. All but one of 49 horses in this family had the GYS1 mutation; however 46% of these horses also had another mutation (RYR1) causing malignant hyperthermia. This is a life-threatening condition that can be triggered by anesthesia, among other things; in horses with this gene mutation, excess calcium is released, causing clinical signs that include muscle rigidity, elevated body temperature, profuse sweating, tachycardia (excessively fast heartbeat), brown urine, hypercapnia (excess carbon dioxide in the blood), creatine kinase (a muscle enzyme) increase, electrolyte disorders, tachypnea (rapid, shallow breathing), hypertension, acidosis (a drop in blood pH), and high mortality. In general, this RYR1 mutation occurs only in about 0.5% of all Quarter Horses.

McCue indicated that most PSSM horses respond well to a high-fat and low-starch diet. However, it appears that while horses with both the GYS1 and malignant hyperthermia mutations respond to this diet, they respond less favorably. On a grain-inclusive diet, 73% of horses with both mutations were unable to reach a treadmill exercise target of a specified time and had to be stopped earlier than horses with GYS1-related PSSM alone. Yet, when fed a high-fat and low-starch diet, only 10% of the double-mutation horses were unable to reach target exercise. It was concluded that both diet and genotype affect clinical expression of rhabdomyolysis.

A genetic test for type-1 PSSM (GYS1) is now available. You can test the blood or hair root of breeds with a high incidence of type-1 PSSM for the GYS1 mutation. For Paints or Quarter Horses with recurring or severe PSSM, testing for malignant hyperthermia mutation as well as GYS1 mutation is recommended. If genetic tests are negative, then a diagnosis of type-2 PSSM or other potential muscle disorders can be pursued through muscle biopsy.

About the Author

Nancy S. Loving, DVM

Nancy S. Loving, DVM, owns Loving Equine Clinic in Boulder, Colorado, and has a special interest in managing the care of sport horses. Her book, All Horse Systems Go, is a comprehensive veterinary care and conditioning resource in full color that covers all facets of horse care. She has also authored the books Go the Distance as a resource for endurance horse owners, Conformation and Performance, and First Aid for Horse and Rider in addition to many veterinary articles for both horse owner and professional audiences.

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