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.

Type 1 PSSM specifically refers to a genetic form of PSSM caused by a mutation in the glycogen synthase 1 (GYS1) gene.

 

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.