PSSM in horses: A summary of the scientific facts
PSSM stands for polysaccharide storage myopathy. This is a group of muscle disorders in which sugar molecules accumulate in the muscle cells, leading to muscle problems. A new genetic test to detect PSSM2 in horses has recently been made available by a laboratory in Germany. This test has caused quite a stir among horse owners and breeders. Discussions about the usefulness and reliability of the test are running high, and the decisions made by some owners based on the test results have gone way too far. The relativity of the test(s) offered is explained in detail on the website of the test (EquiSeq), but this is not clear to everyone. It is therefore high time to summarise the scientific data on PSSM in order to inform all those involved (owners, breeders, buyers and sellers) about PSSM, its various forms and the usefulness of the various tests.
What is PSSM?
Polysaccharide storage myopathy (PSSM) is a collective name for a group of muscular diseases that occur in horses of various breeds. Horses with PSSM may present a variety of clinical symptoms, including muscle stiffness, excessive sweating, unwillingness to walk, reduced performance, loss of muscle, muscle tremors, ER attacks and coffee-coloured urine. These symptoms are sometimes collectively referred to as ‘equine exertional rhabdomyolysis’ (ER) or ‘tying up’, but not every type of ER is PSSM. Blood tests often show an increased concentration of muscle enzymes. Microscopic examination of muscle biopsies from horses with PSSM show abnormal accumulation of sugar molecules in the muscle cells. There are different types of PSSM: PSSM1 and PSSM2. PSSM1 is a well-defined syndrome with an established genetic background, and PSSM2 is a generic term for other muscular diseases that also involve the abnormal accumulation of sugar in muscle cells but do not include the genetic defect that causes PSSM1. PSSM2 is therefore not one specific disease but a collective term for a group of muscle diseases involving the accumulation of sugar molecules in muscle cells.
What is PSSM1?
PSSM1 is a muscle disorder in which there is an abnormal accumulation of sugar molecules in muscle cells caused by a genetic mutation in one specific gene (the so-called glycogen synthase 1 gene – GYS1). This condition occurs in several breeds (e.g. Quarter Horses, Paint Horses and several draught horse breeds). PSSM1 is hereditary (autosomal dominant). This means that it is inherited via one mutation on one gene, as is the case for Warmblood Fragile Foal Syndrome (WFFS), for example – except WFFS is autosomal recessive. This means that, in PSSM1, heterozygotes may present symptoms, and in WFFS, heterozygotes present no symptoms. Each horse has two copies of each gene in its DNA, including the glycogen synthase 1 gene. Horses with two 'healthy' copies for this gene (homozygous healthy) are negative and therefore do not have PSSM1. Horses with one abnormal copy of the gene (heterozygous) are positive and can therefore develop PSSM1 symptoms, often in a mild form. In 50% of cases, these animals will also pass on this gene to their offspring. Horses with two different copies for the gene (homozygous false) for PSSM1 also test positive and will quite often develop a severe form of PSSM1. These animals pass on the gene to 100% of their offspring.
What is PSSM2?
PSSM2 is a group of various muscle diseases that also involve the abnormal accumulation of sugar molecules in the muscle cells, and the symptoms are therefore similar to those of PSSM1. However, these horses do not have the genetic mutation (change) associated with PSSM1 and therefore cannot be detected by the genetic test for PSSM1. The various disorders described under the name PSSM2 can be found in many breeds (various American breeds, KWPN horses, Swedish Warmbloods, Hanoverians, Friesians, Selle Français, Westphalians, Canadian Warmbloods, Irish, Icelanders, Quarter Horses and more). It is currently unknown whether genetic mutation(s) is/are responsible for the conditions that fall under PSSM2, and if so, which. However, a number of genetic variants have been found that may be more prevalent in horses with PSSM2, but these genetic variants are also found in horses that have no clinical problems and do not show sugar accumulation in their muscles. On the other hand, there are also horses with clear clinical signs of PSSM2 (including accumulation of sugar molecules in their muscle cells) that do not have the foregoing genetic variants. In these patients, there must therefore be another cause for the horses to have PSSM2. As such, no direct link has yet been found between certain genetic mutations and the occurrence of PSSM2. It is highly likely that several factors are jointly responsible for the development of the syndromes that are summarised under the term PSSM2.
How can a muscle biopsy help with diagnosis?
A muscle biopsy is an effective method to detect the abnormal accumulation of sugar molecules (PSSM). If an abnormal accumulation of sugar molecules in the muscle fibres is observed, it can be concluded with 100% certainty that the horse is suffering from a form of PSSM. However, the muscle biopsy does not distinguish between PSSM1 (genetic defect that can cause muscle problems to a greater or lesser extent) and PSSM2 (a group of muscle disorders with the same clinical and microscopic abnormalities, but with an as yet unknown genetic background). To make things even more complicated, a horse may be predisposed to PSSM but not yet present with abnormal accumulation of sugar molecules. This is because, in horses suffering from PSSM, it usually takes a while for the abnormal sugar molecules to start to accumulate in the muscle cells and actually become visible in a muscle biopsy. This may occur particularly in young horses that have not yet been trained. This means that a horse with a normal muscle biopsy could still develop PSSM in the future. However, if horses have clinical symptoms due to PSSM, this will always be visible in a muscle biopsy. The examination of a muscle biopsy is therefore particularly useful in horses with clinical muscle complaints. In these cases, if abnormal sugar accumulation is observed in the muscle biopsy, this is a reliable result and therefore PSSM is present. However, it is not yet known what form this will take.
Genetic test for PSSM1: very useful
An effective genetic test is available to detect PSSM1 with almost 100% certainty. This test can be carried out on horses with and without clinical symptoms, as the genetic predisposition is key. Young animals do not always show signs of PSSM1, but a positive genetic test result for PSSM1 will indicate that the animal is likely to develop clinical symptoms of the disease over time. However, this also depends on how the animal is managed. For more information, please also see the article 'PSSM in the horse trade' (PSSM in de paardenhandel) (Tijdschrift voor Diergeneeskunde (Netherlands Journal of Veterinary Science) 2018; 143 (7): 21-23).
How useful is the genetic test for PSSM2?
The situation is more complicated with regard to PSSM2. At present, a great deal of research is being carried out to pinpoint the genetic mutation or mutations that cause PSSM 2. Unfortunately, it has not yet been possible to identify a single genetic mutation that causes PSSM2. This may be because several clinical syndromes are collectively referred to by the name PSSM2. Several genetic variants have been found that may be linked to PSSM2, but these also occur in healthy horses without a PSSM2 disorder (and therefore without sugar accumulation in muscle cells). There are also horses with sugar accumulation in their muscles (demonstrated by way of a muscle biopsy) in which these genetic variants are not detected. As such, there is currently no direct relationship between specific genetic mutations and the syndromes collectively referred to by the name PSSM2. The genetic test that has been made available by the Centre for Animal Genetics (EquiSeq) is, as far as can be ascertained at the moment, not reliable in demonstrating or excluding a muscular disease that falls under PSSM2 with certainty. The test therefore only tells us if a horse has a particular genetic variant that may be more common in horses with PSSM2, but it does not tell us whether the horse has or will develop a muscle disease with sugar accumulation (PSSM2).
How do I keep a horse with PSSM working?
Unfortunately, PSSM cannot be cured. Once a horse has definitively been diagnosed with PSSM, it is crucial to adjust the horse's management in order to prevent ER attacks. There are two crucial aspects in this regard. First, adjust the horse's rations. The amount of sugars in the feed should be restricted. For horses with a high energy requirement (which are not overweight!), fats can be used as an additional energy source. Horses with PSSM also have a higher need for vitamin E, and this should therefore be supplemented. Second, it is very important to give the horse very regular daily exercise to activate the metabolism in the muscles. ER attacks in horses with PSSM occur mainly after several days of rest. No ER attacks have been observed in >75% of horses whose diet and exercise regime had been adjusted. If the horse does show signs of tying up, it is vital to allow the horse to rest in its stall immediately and notify a veterinarian. The veterinarian will be able to provide appropriate treatment depending on the severity of the attack. Depending on the severity, this may include pain relief, drugs to stimulate blood flow to the muscles and infusions to ‘flush out’ harmful waste products from the muscles.
Conclusion
PSSM is a collective term for various muscle disorders in horses. PSSM1 is best demonstrated by way of a genetic test. No reliable genetic test is currently available for PSSM2. The PSSM2 test currently offered is not very useful, as some of the horses that test positive do not have or will not develop sugar accumulation in their muscle cells (PSSM2). It therefore does not seem prudent to make a decision regarding the breeding, selling or even euthanising of horses based on the PSSM2 test that has been made available. A muscle biopsy is currently the best way to detect PSSM2 in horses with clinical symptoms of PSSM (if they test negative for PSSM1).
Mathijs J.P. Theelen, Dr Cornélie M. Westermann, Prof. Marianne M. Sloet van Oldruitenborgh-Oosterbaan
University Clinic for Equine Health, Faculty of Veterinary Medicine, Utrecht University.
For more information, please also see the website of the Equine Neuromuscular Diagnostic Laboratory of Michigan State University (USA): https://cvm.msu.edu/research/faculty-research/valberg-laboratory
For more information (in Dutch only), please click here.