What we know (and still need to learn) about polysaccharide storage myopathy
For the past several hundred years horse owners have struggled to care for charges afflicted with “Monday morning disease,” a crippling condition that affects horses after a day off from work.
“Although owners did recognize the terrible discomfort their horses were in, recall that horses were the primary means of transportation in those days,” says Stephanie Valberg, DVM, PhD, Dipl. ACVIM, ACVSMR. “Time off from tying-up was a major problem, effectively grinding the transportation system to a halt.”
Horse owners didn’t realize the condition’s severity and, so, carried on with their riding and driving as the symptoms cleared. Now, we know Monday morning disease is actually the muscle disorder exertional rhabdomyolysis (ER), more commonly referred to as tying-up, and it must be managed carefully.
If you’ve ever witnessed a horse actively tying-up—sweating, refusing to move, with spasming muscles—the level of discomfort far surpasses that of the usual aches and pains associated with hard work. This is because horses suffering from ER actually have sustained severe muscle damage. In fact, the term exertional rhabdomyolysis is defined as a breakdown or destruction of skeletal muscle cells associated with exercise.
“Tying-up is referred to as a syndrome because it simply describes a collection of clinical signs describing a disease process,” says Valberg. “There are actually many different causes of tying-up, one of which is polysaccharide storage myopathy, or PSSM.”
Valberg, currently the Mary Anne McPhail Dressage Chair in Equine Sports Medicine at Michigan State University, in East Lansing, has dedicated her career to studying equine neuromuscular diseases. Thanks to these efforts and those of other experts worldwide, veterinarians can more rapidly identify specific forms of tying-up, such as PSSM. They can now even differentiate between forms of PSSM—an important distinction when you’re considering treatment.
Perhaps most importantly, research in this field has generated proven exercise- and nutrition-based management strategies for horses affected by the disease. In this article we’ll summarize the steps needed to identify PSSM, distinguish between the types, and offer recommendations for managing affected horses.
You might have heard an owner say, “Oh, my horse tied up this weekend.” But what exactly does that mean, other than an unexpected visit from the veterinarian? And should that owner expect to see more episodes?
“Some horses tie up only sporadically, likely due to factors in the environment,” Valberg says. “For example, horses can tie up when their level of exercise exceeds their training or lack thereof, if they have been overeating, or have a dietary imbalance, such as excesses or deficiencies of certain vitamins or minerals.”
Alternatively, some horses suffer repeated, or chronic, bouts of tying-up. Classic examples, as highlighted in the table below, include malignant hyperthermia (MH) in Quarter Horses and recurrent exertional rhabdomyolysis (RER) in Thoroughbred racehorses.
“PSSM1 and 2 are also classified as chronic causes of tying-up, yet seem to fall into a different category than MH and RER,” says Valberg. “PSSMs appear to have abnormal muscle cell metabolism—the way cells process energy—rather than an abnormality in calcium levels, which are suspected in MH and RER.”
Regardless of the underlying cause, horses suffering from a bout of ER, including PSSM, typically show some or all of the following:
- Excessive sweating;
- Increased heart and respiratory rates;
- Muscle twitching/fasciculations;
- A reluctance or refusal to move; and
- Firm, painful muscles over the back and croup (lumbar and gluteal muscles).
As its name implies, PSSM’s underlying cause is an excessive storage/accumulation of polysaccharides (poly = many, saccharide = sugar)—chains of sugar molecules linked together inside muscle cells.
Cells, including muscle cells, take up these simple sugars such as glucose from the blood after a meal to produce energy. Cells that use a lot of energy store excess glucose for a rainy day in the form of glycogen. Thirty thousand glucose molecules (or more) can bond together to form glycogen inside cells as a backup energy source. While storing a small stash of sugar in muscle cells is a great idea in case of emergencies (the equivalent of your extra coffee pod at work on Monday morning), just a dab will do. Excess glycogen or other polysaccharides can be detrimental, as seen in PSSM-related cases of tying-up.
Currently, we know of two forms of PSSM: The PSSM1 and PSSM2 Valberg mentioned. In both cases veterinarians can take muscle biopsies and apply a special stain to them to examine glycogen in the muscle cells. Horses with abnormally appearing glycogen have PSSM. The next step is to differentiate between types 1 and 2.
Types of Exertional Myopathies Based on Breed
Sporadic exertional rhabdomyolysis due to a horse training or competing beyond its athletic ability, causing muscle damage, electrolyte deficits
Dehydration, electrolyte abnormalities, other
|Thoroughbred, Standardbred||Recurrent exertional rhabdomyolysis thought to be caused by abnormal calcium levels in muscle cells during contraction|
(Hanoverian, Dutch/Swedish/Canadian/Danish Warmblood, Holsteiner, Oldenburg, Trakehner, Rheinlander, others)
Primarily PSSM2; only a small proportion of these breeds appear to suffer from PSSM1
Myofibrillar myopathy, a disruption of the alignment of the contractile proteins called myofibrils in affected horses’ muscle cells.
69% of Percherons and 39% of Belgians in North America and more than 75% of European Belgian horses have the PSSM1 genetic mutation
Clydesdales and Shires rarely have PSSM1
|Quarter Horses and related breeds
Primarily PSSM1, also PSSM2
Malignant hyperthermia caused by a genetic mutation in the ryanodine receptor 1 (RYR1) gene
|Arabians and Arabian-crosses||PSSM2 and myofibrillar myopathy|
|Morgans||PSSM1 or PSSM2|
Polysaccharide storage myopathy was recognized as a distinct disease in 1992. But it wasn’t until 2008 that Molly McCue, DVM, MS, PhD, Dipl. ACVIM, Valberg, and colleagues at the University of Minnesota (U of M) identified an underlying cause: a genetic defect in Quarter Horses.
“Horses with type 1 PSSM have an excess of the polysaccharide glycogen within muscle tissue associated with an autosomal dominant gain-of-function mutation in the GYS1 gene,” says McCue, director of U of M’s Leatherdale Equine Center, in St. Paul.
Let’s break that information down: DNA contains genes that provide the framework for creating proteins, including enzymes such as glycogen synthase that helps make glycogen in muscle cells. Mutations in the DNA can produce faulty proteins. Sometimes those deviant proteins do not function, whereas other times, proteins like glycogen synthase become more active, going above and beyond the call of duty.
The term autosomal means the defective gene occurs on any chromosome except the X and Y “sex” chromosomes. In this case, the GYS1 gene is on ECA10 (equine chromosome 10).
Dominant means only one copy of the gene is needed to cause production of the defective enzyme. Recall that all living organisms have two copies of each gene, one coming from the sire and one from the dam.
Therefore, the GYS1 mutation doesn’t occur on a sex chromosome, requires only one of the two potential copies of the mutation to be effective, and results in excess accumulation of polysaccharides—specifically, glycogen—in muscle cells.
“One of our latest research projects found that horses diagnosed with PSSM1 had the same ‘amount’ of enzyme produced by the GYS1 gene, but that the mutant glycogen synthase enzyme was far more active than the normal enzyme, thereby producing excess glycogen,” says McCue.
Not all horses with the GYS1 mutation for PSSM, however, fully develop PSSM1. Research shows that about 69% of Percherons in America have the GYS1 mutation; however, 69% of those horses do not tie up.
“Multiple factors can influence the development of PSSM1, not just the genetic mutation,” McCue says. “Diet, exercise, other genes for tying-up, such as MH, biological variation, the environment, and a multitude of other genes, can all influence whether PSSM1 actually manifests clinically in a horse.”
This also explains why, as you will find out, rushing straight for a genetic test isn’t necessarily the best place to start if you suspect your horse has PSSM.
Once researchers identified the genetic mutation for PSSM1, they could test all horses with signs of tying-up and confirmed abnormal glycogen for that mutation. In performing this research, Valberg and colleagues realized some cases with abnormal polysaccharides did not have PSSM1. These cases were termed type 2 PSSM. The cause—or more likely causes—for this type of myopathy remains elusive and is the subject of current research.
“We can’t consider PSSM2 one specific disease as yet because we have not identified one or more specific causes,” says Valberg. “PSSM2 actually appears to be caused by different things, depending on breed.”
In other words, just like any horse with PSSM, horses with PSSM2 have abnormal muscle biopsies. The distinguishing feature is they lack the GYS1 mutation.
Of horses diagnosed with PSSM by muscle biopsy, says Valberg, about 28% of Quarter Horses have PSSM2, whereas 90% of Warmbloods and almost 100% of Arabians have PSSM2. Further, Quarter Horses with PSSM2 commonly experience tying-up and have elevated circulating creatine kinase (CK, an enzyme indicating muscle damage). Warmbloods with PSSM2, on the other hand, predominantly exhibit an abnormal gait; reluctance to collect; a mild, shifting lameness; and a less-consistent increase in CK.
Points to Ponder When Diagnosing PSSM
Genetic testing via blood or hair roots for PSSM1 is relatively inexpensive, painless, and very specifically identifies PSSM1. In horses with chronic tying-up that are among breeds known to carry the PSSM1 mutation, genetic testing is a good place to start, says Valberg.
That said, many indicators of PSSM2—poor performance, subtle lameness, topline atrophy (loss of muscling over the back), difficulties changing leads and performing trot/canter transitions, changes in behavior toward work, and sensitivity to grooming—are common complaints that could be caused by a variety of conditions.
“Owners are encouraged to work with their veterinarian to rule out more common causes for these clinical issues before considering muscle biopsies to evaluate horses for PSSM2,” Valberg says.
Only after a complete diagnostic workup has exhausted more common explanations for the presenting complaints (e.g., lameness, neurologic conditions) should owners pursue testing.
To further reinforce this, muscle biopsy results are, like many other diagnostic tests in veterinary medicine, subjective.
“This means that without a proper workup, horses can be falsely diagnosed with PSSM. This translates into instituting inappropriate or ineffective treatments that could prolong time off from work or even (lead to) early retirement,” Valberg says.
Managing the Disease
Valberg says horses with PSSM1 improve markedly with a combination of a customized diet and routine exercise.
“Diet alone will not fix these horses,” she stresses.
Implement a structured exercise protocol, as well as turnout (using a grazing muzzle if pastures are lush). And as long as your horse is not actively tying up, do not give him time off from exercise.
In terms of diet, the goal is to trick the muscle into burning that excess glycogen to fuel the muscle cells, instead of storing it, and to use fat as an alternate energy source.
The “best” diet for a horse with PSSM1 depends on his current clinical condition, body condition score, and fitness level. In general, says Valberg, there are five key nutritional goals when it comes to managing horses with PSSM1:
- Offer hay that’s <12% nonstructural (water-soluble) carbohydrates, which contain high levels of sugar. Recall that the exuberant GYS enzyme (encoded from the GYS1 gene) converts excess sugar to glycogen that accumulates in muscle cells.
- How much hay to offer depends on the horse’s body condition. It is important to achieve and maintain an optimal body condition score (~5 or 6 out of 9) in affected animals.
- If horses require additional energy (e.g., those still in moderate work), offer oil top-dressed on hay cubes or rice bran (naturally high in fat and low in sugar). Generally, 13% of calories fed to a horse daily in the form of fat provides enough energy to allow him to work normally.
- Offer a vitamin and mineral ration balancer (designed to provide a horse with required nutrients that can’t be met with forage alone) if needed.
- Again, use a grazing muzzle when turning horses out on lush pasture. Turn out every day in as large a pasture as possible and as often as possible to keep these horses moving.
Most research regarding management has been done in horses with PSSM1 because Valberg maintained a herd of type 1 horses when she was at U of M and performed controlled diet and exercise trials on them. No controlled management trials have been performed on horses with PSSM2.
“Until now the recommendations for both PSSM1 and PSSM2 have been similar, even though we don’t know what causes PSSM2,” Valberg says.
She and her research team recently explored whether the above-described management recommendations applied to both groups of PSSM horses.
“We applied the same management strategies to horses with PSSM2 and found that Quarter Horses responded remarkably well to the same diet and exercise regimes used for PSSM1 horses,” she says. “In terms of Warmbloods, approximately 80% showed improvements, but many horses didn’t achieve the level of athleticism that owners expected. The Warmblood results, therefore, weren’t as impressive as the Quarter Horses, but it appears we are still moving in a very positive direction.”
Researchers are continually trying to devise more targeted management strategies to help horses afflicted with PSSM.
“Our research relies heavily on samples submitted to our laboratory, and the bulk of those are from horses suspected of having PSSM or other causes of tying-up,” says Valberg. “We are grateful for these samples, of course, but what we are in dire need of is samples from healthy horses, apparently free from PSSM, to compare our abnormal samples to.”
Once her team has accumulated a “library” of samples, they can compare normal and abnormal samples to help address their remaining questions about PSSM, she says. For instance, why does having an accumulation of polysaccharides in muscle tissue cause muscle dissolution? One hypothesis thrown around over the years is that the polysaccharide inclusions (abnormal structures) disrupt the muscle cells’ ability to contract.
“We don’t exactly know why having too much glycogen causes ER, but my research team has been working on answering this question,” says McCue. “We hypothesize that too much glycogen causes the muscle cell to think it doesn’t need to generate energy—a sort of negative feedback loop. We have some data to support this hypothesis and hope to submit a paper soon for publication.”
With owner and veterinary assistance researchers like Valberg and McCue can continue toiling in their laboratories, finding new pieces of information to add to their already impressive knowledge base.
For additional information on PSSM, watch Valberg’s free webinar at MyHorseUniversity.com/single-post/PSSM-Disease or listen to her describe the disease at TheHorse.com/34071.