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Orlando Paciello » 10.Polysaccharide storage myopathy


Polysaccharide storage myopathy

  • This kind of myopathy, known by the acronyms EPSM, PSSM, or EPSSM, is more normally found in quarter horses, warmbloods, Arabs, Morgans, American ponies and in heavy draft horses.
  • Not all affected horses present with evident clinical signs of muscle dysfunction.
  • It is believed to be a hereditary autosomal dominant disease.
Horse with PSSM shows slight lameness during exercise

Horse with PSSM shows slight lameness during exercise


Polysaccharide storage myopathy (cont.)

Affected horses seem to have more rapid glucose absorption from blood compared to control sample but the exact mechanism is not yet known. 
Histologically there is an abnormal accumulation of glycogen in the cytoplasm (PAS positive and amylase sensitive) within the type II fibres.
 In some cases the glycogen aggregates are ubiquitinated, and resistant to amylase in inclusions, composed of glycogen and filamentous protein.

Accumulation of glycogen in cytoplasm. PAS stain

Accumulation of glycogen in cytoplasm. PAS stain

Ubiquitinated glycogen aggregates in the cytoplasm. Immunohistochemistry

Ubiquitinated glycogen aggregates in the cytoplasm. Immunohistochemistry


Polysaccharide storage myopathy (cont.)

Clinical signs are variable, but it is thought that all of them are the result of insufficient energy production on the part of affected muscle fibres.  
It is possible that the abnormal myofibre function is due to changes in the architecture as a result of deposits of complex polysaccharides. However, the excellent response to treatment, even in horses with myofibre inclusions, suggests that abnormal myofibre function depends more on changes to energy metabolism than to deposits of complex polysaccharides.

Glycogen deposits between the myofibrils (arrows). Immunohistochemistry

Glycogen deposits between the myofibrils (arrows). Immunohistochemistry


Polysaccharide storage myopathy (cont.)

Clinic signs include recurrent rhabdomyolysis after exertion but more often the animal presents with an unexplained lameness in pelvic limbs. Affected horses may also have rigid gait, symmetrical muscle atrophy, backpain, muscle cramps which lead to flexion anomalies in the rear limbs with characteristic fasciculation and/or tremor, and bilateral weakness in the pelvic limbs or generalized weakness.

Serious lameness observable in R. ant. limb

Serious lameness observable in R. ant. limb


Polysaccharide storage myopathy (cont.)

In draft horses, as the illness progresses, the animal may suddenly be unable to remain standing, or may be unable to return to a standing position after anaesthesia. CK and AST levels are noticeably higher after episodes of exertional rhabdomyolysis, but they can be slightly or moderately raised in affected horses even after exercise or after lying down. Normal CK and AST levels in these animals points to a kind of muscle dysfunction which is not associated with necrosis.

Lameness in pelvic limb

Lameness in pelvic limb


Polysaccharide storage myopathy (cont.)

  • Muscles look pale pink or are generally red-coloured, so may be confused with autolytic lesions.
  • In draft horses, chronic myopathy can lead to atrophy of the muscles but even if the muscle dimension remains normal, pale striations may still be visible where the muscle fibres have been replaced by adipose tissue.
  • The more seriously affected muscles are the proximal thigh muscles and the epaxial back muscles (for example, longissimus), though any muscle group, including the pectorals and shoulder girdle can be affected.
Longissimus dorsi muscle with serious degeneration of myofibre

Longissimus dorsi muscle with serious degeneration of myofibre


Polysaccharide storage myopathy (cont.)

The kidneys in horses that have died of serious rhabdomyolysis are swollen and dark (pigmentary nephrosis) because of myoglobinuria. 
Myofibral necrosis can vary and be more or less visible depending on its extent. Massive necrosis or regeneration can be seen after a serious episode of rhabdomyolysis whereas in horses in decubitus there are numerous, small foci of necrosis.

Positive intracytoplasmic material with PAS reaction because of the glycogen

Positive intracytoplasmic material with PAS reaction because of the glycogen


Polysaccharide storgae myopathy (cont.)

So far, a diagnosis of polysaccharide storage myopathy is based on finding histopathologic lesions on muscle biopsy of horses showing clinical signs of the disease. Preferred sites for the biopsy are glutei, semimembranosus or semitendinosus although lesions have also been noted in longissimus, especially in horses with a tendency to back pain.

Preferred site for biopsy of semitendinosus indicated in cases of suspected polysaccharide storage myopathy.

Preferred site for biopsy of semitendinosus indicated in cases of suspected polysaccharide storage myopathy

Preferred site for biopsy of semitendinosus indicated in cases of suspected polysaccharide storage myopathy


Polysaccharide storage myopathy (cont.)

Treatment involves changing the animal’s diet to minimise consumption of starch and sugars (less than 15% of total daily calorie intake) and increase that of fats (at least 20% – 25% of the daily total of calories should come from fats). Cereals are replaced with feeds containing more fibre and less starch and less sugar, and fats are added in the form of vegetable oil, powdered fats and supplements containing large amounts of fats or rice bran.  
Animals must be allowed periods of grazing or in a paddock and regular exercise should be guaranteed where possible. 
This treatment is effective in the majority of cases.

Glycogen-dividing enzyme deficiency (glycogenosis type IV)

A congenital, autosomal recessive disease, due to the loss of a glycogenic enzyme, the glycogen branching enzyme (GBE). It is a new disease which affects quarter horses and American paint horses.
The disease can cause miscarriage or still births, or the foals are born weak or with contractures, rhabdomyolysis or cardiac defects in the early stages of development.

Foal with contractures. Photo by kind permission of prof.ssa M.P. Pasolini

Foal with contractures. Photo by kind permission of prof.ssa M.P. Pasolini


Polysaccharide storage myopathy (cont.)

The GBE deficiency leads to the formation of long unbranched glucose chains inside the cells which causes abnormal aggregates of glycogen to form.
These molecules need to be normally converted to glycogen in the presence of GBE. This is the final step of glycogen formation. There are no specific macroscopic lesions. Foals that die as a result of cardiac insufficiency may present with pulmonary edema.

Polysaccharide storage myopathy (cont.)

Typical histological lesions are characterised by rounded hyaline inclusions similar to amylopectin (polyglucosan bodies) within skeletal and cardiac myocytes, especially in the Purkinje fibres, and to a lesser extent in the hepatocytes.
There are also inclusions in the brain and spinal cord and, unlike glycogen, these are PAS positive but resistant to amylase digestion. As with other carbohydrate metabolic disorders, it is believed that failure to produce energy, or the loss of architecture because of the amylopectin deposits, leads to cell dysfunction.

Polyglucosan bodies in a muscle fibre

Polyglucosan bodies in a muscle fibre


Polysaccharide storage myopathy (cont.)

Analysis of peripheral blood and skeletal muscle for GBE activity will identify affected animals, as levels of GBE activity will be seriously reduced in those already sick and moderately reduced in female carriers.
A DNA test is now available using hair from a horse’s mane or tail to identify carriers of the disease. There is, however, no treatment for this disease.

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