Genetic Welfare Problems of Companion Animals

An information resource for prospective pet owners

Quarter Horse

Quarter Horse

Polysaccharide Storage Myopathy

Related terms: equine polysaccharide storage myopathy; tying up; rhabdomyolysis; exertional rhabdomyolysis; equine rhabdomyolysis; set fast; Monday morning disease; azoturia

Outline: In polysaccharide storage myopathy there is breakdown of skeletal muscle as a result of abnormal accumulation of glycogen in muscle cells. This occurs because of the effects of a mutant gene. Affected animals experience episodes of muscle stiffness and pain which can range from mild to severe. In severe cases, release of the protein myoglobin from disrupted muscle cells causes kidney damage and death may occur due to kidney failure. A genetic test is available which enables detection of animals that have the gene that causes the most common form of this disease.


Summary of Information

(for more information click on the links below)

1. Brief description

Polysaccharide storage myopathy (PSSM) is a disease in which skeletal muscle is damaged as result of an abnormality of glycogen metabolism, caused by a mutant form of the gene that controls this. Because the damaged muscle does not function properly, affected horses move stiffly (hence one of the other terms for the condition - 'tying up' syndrome) or are lame. There can be serious 'knock on' effects also, as substances released from the damaged muscle into the bloodstream affect other tissues. During bouts of muscle damage, the protein myoglobin is released into the blood stream and may be excreted in the urine giving it a distinctive red or brown colour. High concentrations of myogloblin in the blood can cause kidney damage and failure leading to death.

2. Intensity of welfare impact

Rhabdomyolysis – muscle breakdown - always causes pain and dysfunction to some extent. The severity ranges from mild to severe. Most horses with PSSM show obvious pain. They may show signs of lameness but muscle pain probably persists when the muscles are at rest.  The metabolic complications of the condition (eg myoglobin and other muscle breakdown products in the blood) probably also make the horse feel ill. In one study it was reported that 13% were unable to stand and were forced to lie down and 14% died (Firshman et al 2003). Managing horses with PSSM requires control of exercise and diet and these interventions may themselves have adverse welfare impacts.

3. Duration of welfare impact

PSSM can occur at any age (Firshman et al 2003, McCue et al 2009). It is unusual in foals and this may be because they are not forcibly exercised and they will tend to rest if they experience any muscle pain (De La Corte et al 1999). Affected animals typically have repeated episodes of the disease, despite changes in management and feeding (Firshman et al 2003). In one study, acute episodes were found to last for more than two hours in 30% of cases and 13% became recumbent and 14% died (Firshman et al 2003).

4. Number of animals affected

It has been estimated, from examination of muscle biopsies collected from 164 quarter horses with no history of signs of the condition, that between 6 and 12 % of quarter horses in the USA are affected (McCue & Valberg 2007).

5. Diagnosis

The disease is suspected when the typical clinical signs are seen, especially when associated with exercise. Blood and urine tests from affected animals show abnormal levels of muscle enzymes. Diagnosis of the type of disease is aided by muscle biopsy. A genetic test for the mutation that causes PSSM type I is available and this may be used as an aid to diagnosis (http://www.cvm.umn.edu/vdl/ourservices/equineneuromuscular/home.html).

6. Genetic

It has been known for a long time that quarter horses were often affected by exertional rhabdomyolysis and that some family lines were particularly prone to the disease (Valberg et al 1992; 1996). Initially it was thought that a recessive gene was responsible for PSSM (Valberg et al 1996). However, it is now suggested that the gene that causes type I PSSM is dominant, that is it need only inherit one copy of the gene to develop the disease (http://www.cvm.umn.edu/umec/lab/Advances_in_PSSM/home.html). The gene that causes this form of the disease was recently discovered (McCue et al 2008).

The genetic cause or causes of type II PSSM are currently unknown (Keen 2011).

(The mutation causing PSSM occurs also in some other horse breeds, more commonly found in the UK (Stanley et al 2009)).

7. How do you know if an animal is a carrier or likely to become affected?

It is believed that the gene causing type 1 PSSM is dominant so all individuals with this mutant gene are at risk of developing the disease. A genetic test is available and horses can be tested at any age (http://www.cvm.umn.edu/umec/lab/Advances_in_PSSM/home.html)

The genes responsible for type 2 PSSM are not known and it is not known if the genes can be passed on to offspring by animals which have shown no signs of the disease themselves.

8. Methods and prospects for elimination of the problem

Since there is now a test for the gene that causes type 1 PSSM, it should be possible to eliminate it from the population by breeding only from animals that do not have this gene. Since it is thought that the type 2 disease also has a genetic basis, it seems wise to avoid breeding from animals that have shown signs of the disease or which have close relatives which have had it.


For further details about this condition, please click on the following:
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1. Clinical and pathological effects

Polysaccharide storage myopathy (PSSM) is a disease in which skeletal muscle is damaged as result of an abnormality of glycogen metabolism. This is caused by the inheritance of a mutant form of the gene that controls this. There are two types of this myopathy. Type I PSSM is due to a mutation of the glycogen synthase gene 1 (GYS1) (McCue et al 2008). The other type, Type II, encompasses the cases of PSSM that are also likely to have a genetic basis but which are known not to be due to the GYS1 gene mutation (Keen 2011).

The glycogen synthase I gene mutation results in production of an abnormal form of the glycogen synthase enzyme that makes it more active than normal. As a result, muscle cells become more sensitive to the hormone insulin and take up more glucose than normal. The excess glucose is converted into the more complex carbohydrates glucose-6-phosphate and, especially, glycogen (Valberg et al 1999, McCue et al 2008). When a muscle biopsy from an affected horse is examined under the microscope the affected cells can be seen to be full of glycogen (McCue et al 2009). The excessive build up of glycogen leads to damage of the muscle cells, and their breakdown, leading to a release of various substances into the bloodstream.

Because the damaged muscle does not function properly, affected horses move stiffly (hence one of the other terms for the condition 'tying up' syndrome) or are lame. Typically the muscles of the legs and the back are affected and become stiff and swollen. The disease can have a sudden onset, and as it progresses the horse may be unable to stand and has to lie down. The muscle damage is painful so affected animals are reluctant to move. Body temperature may be raised and the animals may show other signs of distress such as sweating and vocalising (Firshman et al 2003). It has been suggested that 14% of affected animals die due to the disease (Firshman et al 2003).

If repeated, less severe episodes occur then the horse may become chronically stiff or lame and may show muscle wastage and be unable to exercise normally (Firshman et al 2003).

One of the substances released into the blood as a result of the glycogen-induced muscle cell breakdown is myoglobin. This protein is involved in provision of oxygen for energy metabolism in the cells. The myoglobin is excreted by the kidneys and the urine of affected animals may have a distinctive red or brown colour. This was seen in 10% of the cases reported by Firshman et al (2003). High levels of myogloblin in the blood result in kidney damage and, if this is severe, there can be fatal kidney failure. It has been reported that 70-90% of horses with severe rhabdomyolysis (of whatever cause) die despite intensive care (Keen 2011).

Horses with the genetic abnormality are at risk of episodes of PSSM. This risk can be reduced to some extent by careful management of feeding and exercise (Firshman et al 2003).

Some quarter horses have a concurrent genetic abnormality causing a condition called malignant hyperthermia (resulting in high body temperature) and it seems that horses with both conditions tend to suffer from more severe and longer lasting muscle pain. Malignant hyperthermia is caused by a known genetic defect in the RYR1 gene (Valberg 2011).

(Other diseases can also cause rhabdomyolisis like that which occurs in PSSM and which can cause similar signs. These have been reviewed by Keen (2011)).

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2. Intensity of welfare impact

Rhabdomyolysis – muscle breakdown - always causes pain and dysfunction to some extent. The severity ranges from mild to severe. Most horses with PSSM show obvious pain. They may show signs of lameness but muscle pain probably persists when the muscles are at rest. The metabolic complications of the condition (eg myoglobin and other muscle breakdown products in the blood) probably also make the horse feel ill. In one study it was reported that 13% became recumbent and 14% died (Firshman et al 2003).

Managing horses with PSSM requires control of exercise and diet and these interventions may themselves have adverse welfare impacts.

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3. Duration of welfare impact

PSSM can occur at any age (Firshman et al 2003, McCue et al 2009). It is unusual in foals and this may be because they are not forcibly exercised and they will tend to rest if they experience any muscle pain (De La Corte et al 1999). Affected animals typically have repeated episodes of the disease, despite changes in management and feeding (Firshman et al 2003). In one study, acute episodes were found to last for more than two hours in 30% of cases (Firshman et al 2003).

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4. Number of animals affected

It has been estimated, from examination of muscle biopsies collected from 164 quarter horses with no history of signs of the condition, that between 6 and 12 % of quarter horses in the USA are affected (McCue & Valberg 2007).

(One study of 572 horses diagnosed with exertional rhabdomyolysis in the USA found that 40% of these cases were due to PSSM (diagnosed by examination of muscle biopsies). Of these horses, 63 % were quarter horses or quarter horse crosses (McCue et al 2006). A similar survey in the UK found that 24 (65%) of 37 horses with severe rhabdomyolisis had the mutant GYS1 gene (Stanley et al 2009). This mutation was found only in more severely affected horses and not in the mildly affected horses or those with normal muscles. The mutation has been found in a number of other breeds too.)

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5. Diagnosis

Rhabdomyolisis (muscle breakdown) is suspected when the typical clinical signs are seen, especially when associated with exercise. Blood and urine tests from affected animals show abnormal levels of muscle enzymes (creatine kinase, lactate dehydrogenase and aspartate transaminase). Diagnosis that the rhabdomyolisis is due to PSSM is aided by examination of muscle biopsies. A genetic test for the mutation that underlies PSSM type I is available and may be used as an aid to clinical diagnosis (http://www.cvm.umn.edu/vdl/ourservices/equineneuromuscular/home.html).

A suggested scheme for diagnosing the cause of an episode of exertional rhabdomyolysis using muscle biopsy and genetic testing is outlined at http://www.cvm.umn.edu/umec/lab/Advances_in_PSSM/home.html.

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6. Genetics

It has been known for a long time that quarter horses were often affected by exertional rhabdomyolysis and that some family lines were particularly prone to the disease (Valberg et al 1992, 1996). Initially it was thought that a recessive gene was responsible for PSSM (Valberg et al 1996), meaning that horses needed to inherit two copies of the defective gene to suffer from the disease. However, it is now suggested that the gene that causes type I PSSM is dominant - ie they need only inherit one copy of the gene to develop the disease (http://www.cvm.umn.edu/umec/lab/Advances_in_PSSM/home.html). The gene that causes this form of the disease was recently discovered (McCue et al 2008).

The genetic cause or causes of type II PSSM are currently unknown (Keen 2011).

(The mutation causing PSSM occurs also in some other horse breeds, more commonly found in the UK (Stanley et al 2009)).

Return to top

7. How do you know if an animal is a carrier or likely to become affected?

It is believed that the gene causing type 1 PSSM is dominant so all individuals with this mutant gene are at risk of developing the disease. A genetic test is available and horses can be tested at any age (http://www.cvm.umn.edu/umec/lab/Advances_in_PSSM/home.html)

The genes responsible for type 2 PSSM are not known and it is not known if the genes can be passed on to offspring by animals which have shown no signs of the disease themselves.

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8. Methods and prospects for elimination of the problem

Since there is now a test for the gene that causes type 1 PSSM, it should be possible to eliminate it from the population by breeding only from animals that do not have this gene. Since it is thought that the type II disease also has a genetic basis, it seems wise to avoid breeding from animals that have shown signs of this form of the disease also or which have close relatives which have had it.

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9. Acknowledgements

UFAW is grateful to Rosie Godfrey BVetMed MRCVS and David Godfrey BVetMed FRCVS for their work in compiling this section and to Nina Taylor for her contribution to it.

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10. References

De La Corte FD, Valberg SJ, MacLeay JM and Mickelson JR (1999) Developmental onset of polysaccharide storage myopathy in 4 Quarter Horses. Journal of Veterinary Internal Medicine 16: 581-7

Firshman AM, Valberg SJ, Bender JB and Finno CJ (2003) Epidemiological characteristics and management of polysaccharide storage myopathy in quarter horses. American Journal of Veterinary Research 64: 1319-27

Keen J (2011) Diagnosis and management of equine rhabdomyolysis. In Practice 33: 68-77

McCue ME, Ribiero WP and Valberg (2006) Prevalance of polysaccharide storage myopathy in horses with neuromuscular disorders. Equine Veterinary Journal supplement 36: 340-4

McCue ME and Valberg SJ (2007) Estimated prevalence of polysaccharide storage myopathy among overtly healthy Quarter Horses in the United States. Journal of the American Veterinary Medical Association 231: 746-50

McCue ME, Valberg SJ, Miller MB, Wade C, DiMauro S, Akman HO and Mickelson JR (2008) Glycogen synthase (GYS1) mutation causes a novel skeletal muscle glycogenosis. Genomics 91: 458-66

McCue ME, Armién AG, Lucio M, Mickelson JR and Valberg SJ (2009) Comparative skeletal muscle histopathologic and ultrastructural features in two forms of polysaccharide storage myopathy in horses. Veterinary Pathology 46: 1281-91

Stanley RL, McCue ME, Valberg SJ, Mickelson JR, Mayhew IG, McGowan C, Hahn CN, Patterson-Kane JC and Piercy RJ (2009) A glycogen synthase 1 mutation associated with equine polysaccharide storage myopathy and exertional rhabdomyolysis occurs in a variety of UK breeds. Equine Veterinary Journal 41: 597-601

Unger-Torroledo L, Straub R, Lehmann AD, Graber F, Stahl C, Frey J, Gerber V, Hoppeler H and Baum O (2010) Lethal toxin of Clostrium sordellii is associated with fatal atypical equine myopathy. Veterinary Microbiology 144: 487-492

Valberg SJ (2011) Equine exertional rhabdomyolysis: management of sporadic exertional rhabdomyolysis. http://www.aaep.org/health_articles_view.php?id=210 accessed 7. 10.2011

Valberg SJ, Cardinet GH 3rd, Carlson GP and DiMauro S (1992) Polysaccharide storage myopathy associated with recurrent exertional rhabdomyolysis in horses. Neuromuscular Disorders 2: 351-9

Valberg SJ, Geyer C, Sorum SA and Cardinet GH 3rd (1996) Familial basis of exertional rhabdomyolysis in quarter horse-related breeds. American Journal of Veterinary Research 57: 286-90

Valberg SJ, Macleay JM, Billstrom JA, Hower-Moritz MA and Mickelson JR (1999) Skeletal muscle metabolic response to exercise in horses with ‘tying-up’ due to polysaccharide storage myopathy. Equine Veterinary Journal 31:43–47

http://www.cvm.umn.edu/vdl/ourservices/equineneuromuscular/home.html accessed 12.10.2011

http://www.cvm.umn.edu/umec/lab/Advances_in_PSSM/home.html accessed 12.10.2011

© UFAW 2012


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