Polysaccharide storage myopathy (PSSM) is a genetic disease where both normal and abnormal glycogen are stored in muscle. The condition was originally described in Quarter Horses, but it is now recognized in a variety of different breeds. There are two subtypes of the disease, PSSM type 1 and PSSM type 2. PSSM type 1 is caused by a genetic mutation of the glycogen synthase 1 gene (GYS1). The basis of PSSM type 2 remains unclear, although the GYS1 mutation is not present in these horses.

PSSM Type 1

The genetic mutation behind PSSM1 has been identified in more than 20 breeds.

A UK study identified the mutation in a variety of breeds, including Quarter Horses, Appaloosas, Warmbloods, Connemara crosses, Cobs, Polo Ponies and some Thoroughbred crosses.

A US study reported the mutation in Shires, Morgans, Appaloosas, Quarter Horses, Paints, Exmoor ponies, Saxon-Thuringian Coldbloods, South German Coldbloods, Belgians, Rhenish German Coldbloods, and Percherons.

The defect has also been noted in Clydesdales, although the prevalence in Clydesdales and Shires is less than Belgians and Percherons. Prevalence estimates of PSSM1 in Quarter Horses range from 6-10%, and 6-8% for Paints and Appaloosas. Within the QH breed, PSSM1 occurs most commonly in halter horses (28% affected). PSSM1 is rare (or non-existent) in purebred Standardbreds, Thoroughbreds, or Arabians, but can be seen in crosses.

Genetics of PSSM1

PSSM1 is an autosomal dominant disease. The mutation is a single base pair substitution in the GYS1 gene which encodes for the skeletal muscle form of glycogen synthase. It is referred to as a “gain of function” mutation – this leads to unregulated enzyme activity in affected animals.

Clinical signs of PSSM1

There is wide variability in the severity of signs, dependent on genetics (homozygous versus heterozygous), the degree of exercise, diet, and environmental factors. Riding horses usually begin to show clinical signs around 5 years of age, but this can vary between 1 and 14 years.

Affected horses are characterized by repeated episodes of exertional rhabdomyolysis (ER), often induced with very light exercise. Sixty percent of PSSM horses develop clinical signs while under saddle, and of those, 63% were exercised for <20 minutes. Although exercise is the most common trigger, QH and Paint foals and weanlings with PSSM may also develop clinical rhabdomyolysis in conjunction with other systemic illnesses. Horses with PSSM may have persistently increased CK levels indicating subclinical rhabdomyolysis.

Clinical signs can include fine muscle tremors (fasciculations) and stiffness, a general reluctance to move, sweating, firm muscles on palpation (most commonly in the hind quarters), and recumbency in about 10% of cases. Chronic signs of PSSM1 in riding horses may include exercise intolerance and reduced athletic performance. In severe cases there may be rapid muscle loss over a short period of time. Most of these horses with moderate to severe episodes will have brown discoloured urine, due to the presence of myoglobin (from muscle breakdown) in the urine.

A horse with a severe episode of PSSM1, with substantial muscle loss over 21 days

Brown discolouration of the urine caused by myoglobin

To complicate things there is a second genetic mutation in the ryanodine receptor, RYR1, that is strongly associated with PSSM1. This has been identified in Quarter Horses and when expressed together (RYR1 and PSSM1) results in severe disease and a poor response to treatment.

The signs in Draft breeds are typically less severe and signs aren’t typically seen until around 8 years of age. Many horses, particularly those that are heterozygous can remain without symptoms for life. Those that are homozygous can show acute and severe signs of muscle damage but this is fairly unusual. There may be signs of progressive weakness and muscle loss without increases in CK.

Diagnosis of PSSM1

The diagnosis is based on breed, age and clinical signs. Episodes of exertional rhabdomyolysis (ER) will typically be associated with creatine kinase (CK) levels in excess of 35000 U/L. Between episodes of ER it is not uncommon to have mild increases in CK values at rest. An exercise test is helpful in identifying cases. This involves 3 minutes of walking followed by 12 minutes of trotting and comparing the CK concentration immediately before exercise and then 4 hours later. Typically, affected horses will have a greater than threefold increase in CK concentration.

Definitive diagnosis of PSSM1 is made by genetic testing for the GYS1 mutation on hair root samples. I have recently been using Practical Horse Genetics, based in Sydney.

PSSM Type 2

There is no genetic test for the diagnosis of PSSM2. Consequently, a diagnosis of PSSM2 is based on breed, clinical signs, a negative test for the GYS1 mutation, and a positive muscle biopsy. This form is more common Warmbloods, particularly Dutch Warmbloods, but has also been reported in Paints, Quarter Horses, Appaloosas, Standardbreds, Morgans, and Thoroughbreds.

Chronic signs of PSSM2 are more frequently related to poor performance than recurrent ER. The mean age of onset of clinical signs in Warmbloods is 8-11 years of age. Warmbloods suffering from PSSM2 had stiffness and gait abnormalities, often with CK and AST levels within normal laboratory ranges.

PSSM 1 and 2 Management

The basis for treating these horses is similar despite the specific cause. Polysaccharide storage myopathy (PSSM) is one of many conditions that can affect the skeletal muscle of horses.

When an episode is suspected or confirmed:

Stop exercise and institute stall confinement
Address any anxiety with acetylpromazine or xylazine
Pain control – careful use of a non-steroidal anti-inflammatory (NSAID) drug (eg firocoxib or flunixin) or butorphanol
Monitor the kidneys closely as dehydration, myoglobinuria +/- NSAIDS can result in acute kidney injury (AKI). Maintenance rate of IV fluids may be indicated
Vitamin E for its anti-oxidant effects
Correct any obvious fluid deficits and electrolyte disturbances

Management after and between episodes:

The key to control is a combination of diet and exercise. Stall rest is only indicated for those experiencing episodes of exertional rhabdomyolysis (ER) and for a minimum time (ideally less than 2 days). It has been shown that these horses benefit from pasture turnout and from daily exercise. Gradual addition of 2-minute intervals per day is often recommended once an ER episode has passed, and days without any work should be minimized.

The principle behind formulation of PSSM diets is to reduce starch and sugar intake, and increase the fat content to decrease the glucose load, increase non-esterified fatty acids (NEFAs) for muscle metabolism, and lower serum insulin concentrations.

There are obvious problems in providing high fat diets to horses that are already overweight. An alternative suggestion is to fast them for 6 hours before their daily exercise. This leads to an increase in NEFA concentration from the breakdown of fat which can in turn be used as a fuel for skeletal muscle. There may be a potential role of SGLT2 inhibitor drugs in some of these horses with concurrent insulin dysregulation and EMS. This remains speculative but a theoretical basis certainly exists.

In order to prevent further increases in insulin, hays should have a nonstructural carbohydrate (NSC) content < 12%. Fat can be added with vegetable oil (soybean, corn, safflower, canola, flaxseed, linseed, or peanut) or rice bran. Vitamin E should also be added to the diet due to the potential oxidant stress of fat. There are also several commercial diets that are low starch, high fat marked specifically marketed for horses with PSSM. They typically contain at least 10-15% fat by weight and less than 20% NSC by weight.