Type 1 PSSM in Horses: Genetic Cause, Symptoms, & Management

Type 1 Polysaccharide Storage Myopathy (PSSM1) is a hereditary muscular disorder in horses that results in abnormal accumulation of glycogen (a stored form of sugar) and an abnormal polysaccharide in the muscles.

Horses with this condition produce too much glycogen in their muscle cells, but are unable to use it all as an energy source during physical activity. Affected horses have altered muscle metabolism and experience muscle soreness and cramping after exercise. Some horses are primarily affected by weakness, especially draft breeds with PSSM.

Type 1 PSSM is caused by a genetic mutation that has been identified in more than 20 horse breeds, particularly in Drafts, Quarter Horses and related breeds.

Maintaining the health of horses with PSSM1 requires careful feeding and management. Affected horses should receive a diet containing less than 10% sugar and starch, and need ample turnout and regular exercise.

Type 1 PSSM in Horses

Polysaccharide Storage Myopathy (PSSM) is an equine metabolic disorder characterized by abnormal or excessive glycogen accumulation in skeletal muscle fibers. In type I there is also accumulation of an abnormal polysaccharide which is a tangle of glycogen molecules.

Glycogen is a stored form of glucose (sugar) that provides energy for the muscles during physical activity, especially during high-intensity and endurance exercises. However, some glucose is being burned at all times and it is critical to the supply of intermediates for the Krebs cycle where both glucose and fats are burned aerobically (in the presence of oxygen).

Horses affected by PSSM cannot fully utilize the stored glycogen within their muscle cells while exercising. This occurs because some of the glycogen they produce is not normal and because their metabolism is geared to storing glucose, not burning it. This leads to an unusual buildup of glycogen, resulting in the breakdown of muscle fibers after exercise.

Clinical signs of PSSM in horses include a lack of energy, reluctance to move forward under saddle, progressive weakness and muscle loss, gait abnormalities, poor performance, and repeated episodes of exertional rhabdomyolysis (commonly known as tying up).

Certain signs tend to predominate in specific breeds: tying-up in Quarterhorses; weakness in Drafts; and back pain and gait abnormalities in Warmbloods.

Glycogen Storage Disease

PSSM is a form of glycogenosis, also known as glycogen storage disease (GSD). GSD is a group of rare inherited disorders characterized by defects in the enzymes or transporters involved in glycogen metabolism.

Humans with glycogenosis experience abnormalities in glycogen storage and utilization, leading to various symptoms and potential health complications. Horses with PSSM have normal glycogen utilization but impaired efficiency of energy generation.

History

Formerly known as “Monday morning disease,” this condition acquired its nickname due to its initial observation in the early 1900s among draft horses. ^[1] Affected horses often showed signs of muscle stiffness, pain, and reluctance to move forward under saddle after an extended period of rest, such as over the weekend.

This condition was also formerly referred to as azoturia, because of the characteristic dark-colored urine that horses would sometimes produce during episodes of tying up. Azoturia describes the presence of nitrogen compounds in urine, indicating the breakdown of muscle proteins, specifically myoglobin.

In 1992, researchers first described abnormal polysaccharide accumulation in the skeletal muscle tissue of Quarter Horses and closely-related breeds, leading them to suspect the presence of an unidentified metabolic disorder. ^[2] This disorder eventually became known as polysaccharide storage myopathy.

In 2008, a subgroup of horses previously diagnosed with PSSM was found to possess an inherited genetic mutation in their glycogen synthase 1 (GYS1) gene. This mutation was determined to be the underlying cause of the increased muscle glycogen concentrations associated with the disorder. ^[1]

Type 1 vs. Type 2 PSSM

PSSM is diagnosed by muscle biopsy findings of abnormal amounts or locations of glycogen in the cells. In the case of PSSM1 there are also abnormal polysaccharide inclusions which stain with PAS (periodic acid Schiff stain) and are resistant to breakdown with amylase, unlike normal glycogen.

To differentiate between forms of the disease, the subset of horses carrying the GYS1 genetic mutation is classified as Type 1 PSSM, while horses lacking this specific genetic mutation are categorized as Type 2 PSSM (PSSM2).

The exact cause of PSSM2 in horses is not yet known, but like PSSM1 it is believed to have a genetic basis. Horses with Type 2 PSSM also exhibit abnormal glycogen amounts or locations in muscle fibers.

One recently uncovered disease that resembles PSSM2 on biopsy is myofibrillar myopathy (MFM). ^[24][25] In this disorder, glycogen pools in disrupted muscle fibers but it is the fiber disruption that is the problem.

It is possible that several other forms of PSSM, or disorders which resemble it on biopsy, also exist. Each may be linked to distinct genetic mutation(s) contributing to the disorder. The exact mechanisms leading to glycogen abnormalities in non-PSSM1 horses are still an active area of research.

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Genetic Cause of Type 1 PSSM

Horses affected by Type 1 PSSM possess a genetic mutation in the GYS1 gene, which is responsible for encoding a crucial muscle enzyme known as glycogen synthase. This enzyme facilitates the conversion of glucose molecules into glycogen for storage in muscle cells.

Horses with PSSM1 have a missense change in their GYS1 gene, specifically at at amino acid position 309 where arginine is replaced by histidine (indicated as p.309Arg>His or p.R309H).

The mutation in the GYS1 gene disrupts the normal function of the glycogen synthase enzyme by increasing its activity, leading to a constant production of glycogen in the muscles. ^[1][3] Glucose being diverted into glycogen is not immediately available for energy pathways.

This mutation also results in the production of glycogen lacking the normal branching structure, impairing its conversion into usable energy. Consequently, there is an abnormal buildup of glycogen within muscle fibers.

Effect of the GYS1 Mutation

In normal horses, stored glycogen undergoes glycogenolysis during exercise to produce glucose so it can be used as fuel. In this process, enzymes work on each of the branches of the highly branched normal glycogen molecule.

Glucose is converted into adenosine triphosphate (ATP), the primary energy currency for cells, and then used to fuel various cellular processes and activities, including muscle contraction and relaxation.

In horses with PSSM1, breakdown of unbranched or poorly branched glycogen is a slow process compared to normal glycogen. Impaired mitochondrial function means they are less efficient in generating ATP. This is also shown by higher than normal levels of IMP, the breakdown product of ATP. ^[26] In normal muscle, most of the ATP is recycled not broken down.

The increased glycogen synthase activity may also impair the oxidative metabolism of other fuel sources for muscle fibers, such as pyruvate and fatty acids. ^[4][22] The biochemistry of the muscle cell is designed so that it cannot burn glucose and make glycogen at the same time.

Genetic Inheritance

The genetic mutation responsible for PSSM1’s can be inherited from one or both parents. It follows an autosomal dominant pattern, meaning that if one parent carries the gene mutation, their offspring will inherit the disorder.

Horses can possess various combinations of the GYS1 gene mutation, with some being homozygous and others being heterozygous. These genotypes (different forms of the gene) are described as follows:

• Homozygous PSSM1 (H/H)
• Heterozygous PSSM1 (H/R)

Homozygous horses have two copies of the mutated gene, one from each parent. Heterozygous horses have one mutated gene and one normal gene.

Horses that are homozygous for PSSM1 are generally more affected by the condition because they tend to exhibit higher glycogen concentrations and increased glycogen synthase activity. ^[3]

Genetic Testing

Horses that are suspected of having Type 1 PSSM, especially those with a breed predisposition, should undergo genetic testing of the GYS1 mutation using whole blood or hair root samples.

A positive test result will confirm the presence of Type 1 PSSM. If your horse tests negative but exhibits symptoms consistent with a muscle disorder, your veterinarian may conduct a muscle biopsy to assess the possibility of Type 2 PSSM or another muscle or neurological disorder. ^[5]

Genetic testing for PSSM1 is important to obtain an accurate diagnosis and determine an appropriate treatment plan. Additionally, it plays a critical role in making informed and responsible breeding decisions.

Prevalence of Type 1 PSSM

The GYS1 mutation that causes Type 1 PSSM has been found in more than 20 different breeds of horses in Europe and North America. Quarter Horses, drafts, and related breeds show a significantly greater prevalence of PSSM compared to light horse breeds. ^{[6][7][8][9][10][11][12][13][14][15]}

Draft breeds derived from Continental Europe, such as Trekpaards, have the highest prevalence of PSSM. ^[6][7][8] On the other hand, draft breeds derived from the United Kingdom, such as Shires and Clydesdales, have a lower prevalence of PSSM. ^[9][10]

Approximately 6 – 10% of Quarter Horses are estimated to be affected by PSSM, and among those diagnosed, 72% are identified as having Type 1 PSSM. Halter Quarter Horses have the highest incidence of PSSM1, while racing Quarter Horses have the lowest incidence.

Quarter Horse related breeds, such as the American Paint and Appaloosa horse, exhibit a similar prevalence of PSSM, with 6 – 8% of horses affected. ^{[11][12][13][14]}

The following is a compilation of the reported prevalence of PSSM in common breeds:

• Trekpaards: 90% of horses
• North American Belgians: 36% of horses
• Percherons: 54% of horses
• Quarter Horses: 6 – 10% of horses
• Appaloosas and Paints: 6 – 8% of horses
• Warmbloods: 18% of horses

Horses with PSSM1 typically start displaying clinical signs around the age of six years. However, there seems to be no specific body type, temperament, or sex preference associated with the disorder. ^[4][14]

Clinical Signs of Type 1 PSSM

The clinical signs observed in horses with PSSM1 are significantly influenced by factors such as age, diet, management practices, and current exercise level. Further research is required to understand the impact of other genes on the disease’s expression and to investigate if seasonal factors play a role in the condition. ^[2]

In general, clinical signs are exacerbated in horses that are unfit or rested and confined for several days before exercise. ^[16] Symptoms are most commonly triggered by exercise lasting less than 20 minutes. ^[17]

Acute Symptoms

Acute presentations of PSSM often result in episodes of exertional rhabdomyolysis (“tying up”), typically occurring shortly after the start of exercise.

In many cases, tying up is a sporadic event caused by issues in the horse’s diet or abrupt changes in exercise intensity. However, if the horse experiences repeated episodes of tying up, it is likely indicative of an underlying muscle condition.

Symptoms of an acute PSSM episode include:

• Tucked up abdomen
• Fasciculations (tremors) in flanks
• Muscle stiffness
• Reluctance to go forward
• Sweating
• Muscle cramping
• Shifting lameness
• Stretching out as if to urinate

Factors that increase the risk of acute PSSM episodes include diets high in nonstructural carbohydrates (NSC), unfit horses returning to work, extended periods of rest, and sudden changes in exercise intensity. ^[4]

Chronic Symptoms

Chronic presentations of PSSM produce less specific symptoms, making these cases more difficult to diagnose. Signs of chronic PSSM include:

• Lack of energy under saddle
• Reluctance to move forward
• Stopping and stretching as if to urinate
• Sour attitude toward exercise
• Poor performance
• Progressive weakness and muscle loss
• Gait abnormalities
• Repeated episodes of tying-up

Risk factors for chronic PSSM include diets high in nonstructural carbohydrates (NSC), irregular exercise, and a lack of turnout. ^[4]

Treatment of Type 1 PSSM

Diagnosing horses with PSSM is often more straightforward after an acute episode due, to the severity of symptoms associated with tying-up. In contrast, horses with chronic presentation of PSSM often experience mild or unspecific symptoms, making their diagnosis more challenging.

If your horse exhibits signs of tying-up, you should stop exercising immediately and call your veterinarian. If possible, return your horse to their stall, but avoid forcing them to walk if they are unable to do so.

Veterinary treatment for an acute episode may involve fluid therapy to address dehydration and medications to alleviate pain and anxiety. Once the horse can walk comfortably again (typically within 12-24 hours), they can then resume turnout in paddocks of gradually increasing size. ^[18]

If your horse shows symptoms consistent with the chronic presentation of PSSM, you should make an appointment with your veterinarian for a full physical and lameness examination.

The exam may include an exercise intolerance test to check for elevations in muscle enzymes. If Type 1 PSSM is suspected, your veterinarian will submit a whole blood or hair root sample for genetic testing.

Nutrition, Exercise, and Management

Proper nutrition and consistent exercise are the two most important factors for managing horses with PSSM. Research shows that PSSM-affected horses benefit from daily exercise, free access to turnout, and dietary modification to reduce sugar and starch intake. ^[14]

Half of horses with PSSM1 experience an improvement in clinical signs solely through nutritional management. Among horses that follow both a nutrition and exercise management program, 90% of horses see a reduction in episodes of typing up. ^[23]

It is important to consult with an equine nutritionist in addition to your veterinarian when caring for a PSSM1 horse to ensure their diet is appropriately formulated and properly balanced.

Diet Plan

The first priority in designing a feeding program for a PSSM horse is to reduce the hydrolyzable carbohydrate (HC) content to 10% or less.

HC is used to describe starch and sugars that will stimulate insulin secretion by the pancreas. This differs from non-structural carbohydrates (NSC) which describes carbohydrates found within plant cells and includes compounds such as fructans which do not stimulate insulin secretion.

By keeping dietary HC content low, you can effectively regulate your horse’s insulin levels and avoid further stimulation of the GYS1 gene. ^[4][19] PSSM horses are more sensitive to insulin.

The second priority in formulating a PSSM diet is to balance your horse’s energy intake to maintain a healthy weight. Horses with PSSM are often easy keepers, making it important to avoid excess calories, which can contribute to weight gain.

Forage

Low-HC forage should form the basis of your horse’s diet and be fed at a minimum rate of 1.5 – 2% of your horse’s body weight or up to 3% for an exercising horse. For a 500 kg (1100 lb) horse at maintenance, this is approximately 10 kg (22 lb) of forage per day.

Forage alone will not meet all of your horse’s nutrient requirements, which is why it is important to feed a balanced vitamin and mineral supplement to prevent nutritional deficiencies.

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Additional calories

If your horse is underweight or required additional calories to meet exercise demands, PSSM horses benefit from adding fat to the diet as an energy source. ^[20]

Unlike traditional grain-based feeds, fat supplements contribute caloric energy to the diet without introducing additional starch and sugar. Increasing dietary fat also enhances the availability of free fatty acids, which may help to promote fat metabolism in muscle tissue. ^[21]

Although studies have provided up to 20% of the calories from fat to PSSM horses, avoid feeding more than 10% of the calories from fat. Diets with very high fat inclusion (10 to 20% of the calories) actually block carbohydrate metabolism and cause insulin resistance. However, inducing insulin resistance does not improve PSSM. ^[27]

Plant-based oils, rice bran, and ground flax are all convenient options for adding fat to the diet. You can also look for fat supplements enriched with beneficial omega-3 fatty acids, such as Mad Barn’s w-3 oil which also contains 1,000 IU of natural vitamin E per 100 ml.

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Additional supplements

Horses with PSSM can also benefit from additional vitamin E and selenium supplementation to support muscle health and function. These antioxidant nutrients play a key role in protecting muscle cells from oxidative damage.

Once the diet is well-balanced and safe energy sources are provided, consider supplementing with acetyl-l-carnitine to support energy metabolism in muscle cells.

Acetyl-L-carnitine, also known as ALCAR, is a naturally occurring metabolite of L-carnitine. It has effects on muscle metabolism and energy production which can support muscle function in PSSM horses.

ALCAR provides substrates for making acetyl-coenzyme A (acetyl-CoA) which enters the Krebs cycle in the mitochondria. Mitochondria are small structures in cells that are known as energy ‘powerhouses’.

Both glucose and fatty acids must be converted to acetyl-CoA before entering the mitochondria to be burned for energy. L-carnitine also stimulates activity of the pyruvate dehydrogenase enzyme complex which converts the pyruvate from glucose metabolism to acetyl-CoA to enter the mitochondria. ^[28]

Another way that ALCAR supports muscle energy metabolism is by activating the enzyme AMP kinase (AMPK). This is a critical regulator of glucose metabolism in cells that diverts glucose away from glycogen storage and into energy pathways. ^[29]

Acetyl-L-carnitine also tells cells to make more mitochondria to further support breaking down glucose and fatty acids into cellular energy. ^[30]

Together these effects of ALCAR can help horses with PSSM use glucose for energy in muscle cells rather than storing it as abnormal glycogen or other polysaccharides.

The recommended feeding rate is 2.2 grams per 100 kg or 1 gram per 100 pounds of body weight. This can be given twice daily for two weeks then once daily.

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Recommended Diet

Table 1: Example diet for a 500 kg (1100 lb) normal weight horse in moderate exercise.

Exercise & Management

While dietary management is critical for horses with Type 1 PSSM, outcomes improve when combined with modifications to the exercise routine and daily management. Make sure to allow allow adequate time for your horse to adapt to any dietary changes before starting exercise.

PSSM horses need a consistent exercise program that allows for a careful and incremental return to work. ^[4][16] Daily exercise helps maintain muscle health by enhancing the utilization of glycogen as an energy source.

Exercise can also enhance the horse’s ability to efficiently utilize fat as an alternative energy source, ensuring a consistent supply of energy during prolonged physical activity.

It is beneficial to give PSSM horses longer warm-ups, and horses should be allowed to work on the lunge in a long and low, stretchy frame prior to ridden work. ^[14] A minimum of 10 minutes of daily exercise is recommended, with the duration increasing as the horse’s fitness level improves.

Turnout is also important for PSSM horses to allow for as much free exercise as possible. Ideally, these horses should have 12 – 24 hours of turnout per day, with limited time in a stall.

Horses on pasture may benefit from a grazing muzzle to help manage their weight while still allowing for plenty of unstructured movement. Spring pastures may be poorly tolerated because of high hydrolyzable carbohydrates (starch and simple sugars – ESC) and because they are often low in magnesium which makes the muscles more irritable.

Prognosis

While there is no cure for Type 1 PSSM, it can be managed effectively to enable affected horses to live a long and healthy life. With adherence to both diet and exercise recommendations, many horses show notable improvements in clinical signs and can return to acceptable levels of performance.

Horses with severe or recurrent clinical signs require more stringent management to regain normal muscle function. Horses with an underlying genetic susceptibility are prone to future events.

If you need help with formulating a diet for your horse with PSSM1, submit their information online to receive a free analysis from our qualified team of nutritionists.