Polysaccharide Storage Myopathy Research Articles

Comparison of Histopathologic Criteria and Skeletal Muscle Fixation Techniques for the Diagnosis of Polysaccharide Storage Myopathy in Horses

The purpose of the study reported here was to determine the effect of three methods of fixation of skeletal muscle biopsy specimens on the histopathologic appearance of muscle sections and to determine criteria that were most consistently associated with a diagnosis of polysaccharide storage myopathy (PSSM) in horses. Surgically excised semimembranosus muscle biopsy specimens were obtained from nine horses previously diagnosed with PSSM and from 15 control horses. Portions of each specimen were fixed in formalin, frozen immediately, and chilled for 24 hours prior to freezing. Sections stained with hematoxylin and eosin (HE), periodic acid-Schiff (PAS), and amylase-PAS were scored for histopathologic criteria by three investigators blinded to the sample origin. The presence of amylase-resistant, abnormal polysaccharide was found to be the most sensitive and specific diagnostic indicator for PSSM, and was readily detected regardless of the fixation technique or investigator. Other less-specific features associated with PSSM included atrophy and cytoplasmic and subsarcolemmal vacuoles; however, their histologic scores varied among fixation technique and investigators. Scores for subsarcolemmal and cytoplasmic amylase-sensitive glycogen in horses with PSSM were similar to those for control horses and varied among fixation techniques. In conclusion, PSSM is most accurately diagnosed in muscle biopsy specimens on the basis of appearance of amylase-resistant, abnormal polysaccharide, not amylase-sensitive glycogen, regardless of fixation technique. In general, frozen sections appeared to be better suited for studying myopathies because many histopathologic features of skeletal muscle were obscured by formalin fixation.

Ubiquitin Expression in Muscle from Horses with Polysaccharide Storage Myopathy

Serial sections of formalin-fixed, paraffin-embedded muscle biopsy specimens from 28 Quarter Horse, Paint, and draft-related breeds, aged 0.5-23 years, were treated with periodic acid-Schiff (PAS) stain for glycogen and were immunostained to detect ubiquitin expression. On the basis of findings in PAS-stained sections, a diagnosis of equine polysaccharide storage myopathy (EPSSM) was made in 22 horses aged 2-23 years (mean, 9.4 years); samples from 6 horses aged 0.5-15 years (mean, 7.3 years) had a normal PAS staining pattern, with no relevant lesions. Ubiquitin expression was detected in all but a 2-year-old EPSSM-affected horse and was not detected in the non-EPSSM-affected horses. Ubiquitin expression was greater than the degree of PAS-positive, amylase-resistant material, and ubiquitin was detected in aggregates of amylase-sensitive glycogen as well as in aggregates of amylase-resistant material. Results suggest that glycogen aggregates develop and are ubiquitinated prior to development of amylase-resistant inclusions. Ubiquitin immunostaining may be most useful for confirming the diagnosis of EPSSM in horses with only amylase-sensitive glycogen aggregates and in horses with early amylase-resistant inclusions. However, ubiquitin immunostaining is no more sensitive than is PAS staining for diagnosis of EPSSM.

Prevalences and clinical signs of polysaccharide storage myopathy and shivers in Belgian Draft Horses

To determine prevalences of polysaccharide storage myopathy (PSSM) and shivers in Belgian Draft Horses (BDHs) and determine whether there was an association between these 2 conditions. Prospective cohort study. 103 BDHs > 1 year old. Owners were questioned regarding clinical signs of PSSM, shivers, and hindquarter weakness, defined as poor hindquarter muscling and lack of propulsion. Blood samples were collected for determination of serum creatine kinase and aspartate transferase activities and serum selenium and vitamin E concentrations. A biopsy sample from the gluteus medius muscle was submitted for histologic, histochemical, and biochemical analysis. A diagnosis of PSSM was made if abnormal amylase-resistant polysaccharide inclusions were seen histologically. 37 (36%) horses had PSSM and 19 (18%) had shivers, but only 6 (6%) had both PSSM and shivers, whereas 31 (30%) had PSSM alone, 13 (13%) had shivers alone, and 53 (51%) had neither, and a significant association between PSSM and shivers was not detected. Hindquarter weakness was found in 30 horses. Only 13 of 37 (35%) horses with PSSM and 11 of 19 (58%) horses with shivers had hindquarter weakness. Serum creatine kinase and aspartate transferase activities and serum selenium and vitamin E concentrations were not significantly different between horses with and without PSSM or between horses with and without shivers. Results suggest that PSSM and shivers are common but unrelated disorders in BDHs.

Incidence of Polysaccharide Storage Myopathy: Necropsy Study of 225 Horses

Muscle samples were obtained at necropsy from 225 horses and ponies 1 year of age or older. Samples were processed in routine manner and were stained with hematoxylin and eosin and with periodic acid-Schiff for glycogen. Sections were examined for abnormal glycogen content and amylase-resistant complex polysaccharide and for chronic myopathic change (excessive fiber size variation, increase in number of internal nuclei). A total of 101 horses and ponies with lesions of polysaccharide storage myopathy were identified. Age of affected horses ranged from one to 30 years, with a mean of 14.7 years. Mean age of nonaffected horses was 12 years. Incidence of polysaccharide storage myopathy varied depending on breed; Thoroughbreds had the lowest (27%) and draft-related horses had the highest (86%) incidence. Chronic myopathic changes were more severe in polysaccharide storage myopathy-affected horses than in nonaffected horses. Results of this study indicate that polysaccharide storage myopathy is a common disorder of many breeds of horses and ponies.

Serum creatine kinase response to exercise during dexamethasone-induced insulin resistance in Quarter Horses with polysaccharide storage myopathy

To determine effects of dexamethasone on insulin sensitivity, serum creatine kinase (CK) activity 4 hours after exercise, and muscle glycogen concentration in Quarter Horses with polysaccharide storage myopathy (PSSM). 4 adult Quarter Horses with PSSM. A 2 x 2 crossover design was used with dexamethasone (0.08 mg/kg) or saline (0.9% NaCl) solution administered IV every 48 hours. Horses were exercised on a treadmill daily for 3 wk/treatment with a 2-week washout period between treatments. Serum CK activity was measured daily 4 hours after exercise. At the end of each treatment period, serum cortisol concentrations were measured, a hyperinsulinemic euglycemic clamp (HEC) technique was performed, and muscle glycogen content was determined. Mean +/- SEM serum cortisol concentration was significantly lower after 48 hours for the dexamethasone treatment (0.38 +/- 0.08 mg/dL), compared with the saline treatment (4.15 +/- 0.40 mg/dL). Dexamethasone significantly decreased the rate of glucose infusion necessary to maintain euglycemia during the HEC technique, compared with the saline treatment. Muscle glycogen concentrations and mean CK activity after exercise were not altered by dexamethasone treatment, compared with the saline treatment. Dexamethasone significantly reduced whole-body insulin-stimulated glucose uptake in Quarter Horses with PSSM after a 3-week period but did not diminish serum CK response to exercise or muscle glycogen concentrations in these 4 horses. Therefore, a decrease in glucose uptake for 3 weeks did not appear to alleviate exertional rhabdomyolysis in these horses. It is possible that long-term treatment may yield other results.

A review of unlikely sources of excess carbohydrate in equine diets

Introduction Equines suffering from laminitis, insulin resistance, Equine Metabolic Syndrome, Cushing’s, osteochondrosis, and equine polysaccharide storage myopathy ( EPSM) require restriction of sugar, starch and/or fructan, which is collectively called Non Structural Carbohydrates (NSC). While there is a great deal of scientific literature in plant science journals regarding factors effecting NSC content of feed and forage, the information is not convenient to veterinarians. The nomenclature that plant scientists use may be unfamiliar to veterinarians, as well as the concepts central to plant physiology. Attempts by some veterinarians to give advice regarding more appropriate feed choices and pasture management practices to owners of carbohydrate intolerant equines may be based on incorrect assumptions, and incomplete understanding of the mechanisms governing NSC concentration in forage. This review is necessary to dispel some frequent misconceptions regarding NSC content of forage. Some forage that may be intuitively perceived as low in feed value, such as dead grass and weeds, may actually be high enough in NSC to trigger symptoms in susceptible animals. Grass founder has always been blamed on ‘lush’ grass. The term ‘lush’ is generally considered to mean green, vigorous, and well hydrated. Advice given by veterinarians on methods to avoid ‘lush’ grass may actually increase NSC concentration. This review will demonstrate how brown, dead or dying, desiccated grass can have surprisingly high levels of NSC, and explain the concepts of plant physiology that govern NSC accumulation in grass. This may explain onset of some previously mysterious cases of endocrinopathic laminitis, or worsening of symptoms in other diseases involving carbohydrate intolerance. There are some common misconceptions about the relative levels of Non Structural Carbohydrate (NSC) in horse feeds. While most horse owners recognize that molasses and grain are high in sugar and starch, they do not realize that excess NSC may be found in other portions of horse rations. This review of the NSC content of the non-grain portion of equine rations may provide practitioners and caretakers with information to fine-tune the diets of CHO intolerant equines.

Role of dietary energy source in the expression of chronic exertional myopathies in horses

Abstract Muscle disorders characterized by the development of pain and stiffness during and after exercise (exertional rhabdomyolysis, ER) are common in horses. Two heritable forms of chronic ER have been identified: 1) polysaccharide storage myopathy (PSSM), a condition characterized in quarter horses and related breeds, but also reported to occur in other breeds; and 2) recurrent exertional rhabdomyolysis (RER) in Thoroughbreds. Although the pathophysiology of PSSM and RER are different, there is epidemiological and experimental evidence that feeding diets rich in hydrolyzable carbohydrates (starch and simple sugars) enhances the phenotypic expression of both disorders. The PSSM is characterized by increased insulin sensitivity, excessive muscle glycogen storage, and the accumulation of amylase-resistant polysaccharide in muscle. The feeding of concentrates rich in hydrolyzable carbohydrates may enhance disease expression by increasing the quantity of glucose available for muscle glycogen synthesis. On the other hand, diets rich in starches and simples sugars may increase clinical expression of RER via enhancement of stress and anxiety, factors known to increase the risk of ER in horses with RER. A decrease in the frequency and severity of ER has been observed when horses with PSSM and RER are fed diets with reduced DE from hydrolyzable carbohydrates (<10 to 15% of total diet) and increased DE from fat (15 to 20%) and other energy sources, such as beet pulp and soybean hulls.

Effects of submaximal exercise on adenine nucleotide concentrations in skeletal muscle fibers of horses with polysaccharide storage myopathy

To determine whether disruption of adenine triphosphate (ATP) regeneration and subsequent adenine nucleotide degradation are potential mechanisms for rhabdomyolysis in horses with polysaccharide storage myopathy (PSSM) performing submaximal exercise. 7 horses with PSSM and 4 control horses. Horses with PSSM performed 2-minute intervals of a walk and trot exercise on a treadmill until muscle cramping developed. Control horses exercised similarly for 20 minutes. Serum creatine kinase (CK) activity was measured 4 hours after exercise. Citrate synthase (CS), 3-OH-acylCoA dehydrogenase, and lactate dehydrogenase activities prior to exercise and glucose-6-phosphate (G-6-P) and lactate concentrations before and after exercise were measured in gluteal muscle specimens. Adenine triphosphate, diphosphate (ADP), monophosphate (AMP), and inosine monophosphate (IMP) concentrations were measured before and after exercise in whole muscle, single muscle fibers, and pooled single muscle fibers. Serum CK activity ranged from 255 to 22,265 U/L in horses with PSSM and 133 to 278 U/L in control horses. Muscle CS activity was lower in horses with PSSM, compared with control horses. Muscle G-6-P lactate, ATP, ADP, and AMP concentrations in whole muscle did not change with exercise in any horses. Concentration of IMP increased with exercise in whole muscle, pooled muscle fibers, and single muscle fibers in horses with PSSM. Large variations in ATP and IMP concentrations were observed within single muscle fibers. Increased IMP concentration without depletion of ATP in individual muscle fibers of horses with PSSM during submaximal exercise indicates an energy imbalance that may contribute to the development of exercise intolerance and rhabdomyolysis.

Diagnosis and treatment of equine polysaccharide storage myopathy

Equine polysaccharide storage myopathy (EPSM) is a recently recognized metabolic condition with a high incidence in many breeds of horses and ponies. Clinical signs are extremely variable, but all can be related to underlying skeletal muscle dysfunction. Therapy employing a high-fat, high-fiber, low-starch, low-sugar diet and as much exercise as possible has proven to be extremely successful in control of this disorder. EPSM is progressive, and early detection and institution of therapy are vital.

The Effect of Varying Dietary Starch and Fat Content on Serum Creatine Kinase Activity and Substrate Availability in Equine Polysaccharide Storage Myopathy

The effect of dietary starch and fat content on serum creatine kinase (CK) activity and substrate availability was evaluated in 4 mares of Quarter Horse‐related breeds with polysaccharide storage myopathy (PSSM). Four isocaloric diets ranging in digestible energy (DE) from 21.2% (diet A), 14.8% (B), 8.4% (C), to 3.9% (D) for starch, and 7.2% DE (diet A), 9.9% (B), to 12.7% DE (diet C and D) for fat were fed for 6‐week periods (4 weeks with exercise) using a 4×4 Latin square design. Postprandial glucose and insulin responses were measured, and 4 hours postexercise, serum CK activity, glucose, insulin, free fatty acids (FFA), and β‐hydroxybutyrate (β‐HBA) were analyzed. Glycogen, glucose‐6‐phosphate, citrate synthase, 3‐hydroxy‐acyl‐CoA dehydrogenase, lactate dehydrogenase as well as abnormal polysaccharide and lipid content were measured in middle gluteal muscle samples. Postprandial insulin and glucose response was higher for diet A versus D. Log CK activity was higher with diets A, B, and C versus D. Daily insulin was higher and FFA lower on diet A versus B, C, and D, whereas glucose varied only slightly with diet. Muscle oxidative capacity and lipid stores were low in PSSM horses and muscle glycogen and abnormal polysaccharide content high on both diets A and D. Individual variation occurred in the response of PSSM horses to diets differing in starch and fat content. However, for those horses with clinical manifestations of PSSM, a diet with <5% DE starch and >12% DE fat can reduce exertional rhabdomyolysis, potentially by increasing availability of FFA for muscle metabolism.

Insulin sensitivity and skeletal muscle glucose transport in horses with equine polysaccharide storage myopathy

Equine polysaccharide storage myopathy (PSSM) is an inherited disorder characterized by the accumulation of glycogen and abnormal polysaccharide in muscle with normal glyco(geno)lytic enzyme activities. The purpose of this study was to evaluate in vivo insulin sensitivity and glucose excursion in PSSM using a euglycemic hyperinsulinemic clamp. In addition, the content of muscle glucose transporters (GLUT1 and GLUT4) and the insulin receptor was determined in muscle biopsies using Western blot analysis. The glycogen content was 1.8-fold higher, and isolated polysaccharide analyzed by iodine absorption spectra, was less branched in equine PSSM. Throughout the clamp, the affected horses required a higher rate of glucose infusion to maintain euglycemia. Although GLUT1 content was lower, the total content of GLUT4 and insulin receptor was not different in myopathic vs. control horses. PSSM therefore represents a novel disorder where enhanced insulin sensitivity and elevated glucose excursion leads to increased synthesis of muscle glycogen, which in our horses appears to be independent of augmented GLUT4 or IR quantity.

The Effect of Varying Dietary Starch and Fat Content on Serum Creatine Kinase Activity and Substrate Availability in Equine Polysaccharide Storage Myopathy

The effect of dietary starch and fat content on serum creatine kinase (CK) activity and substrate availability was evaluated in 4 mares of Quarter Horse-related breeds with polysaccharide storage myopathy (PSSM). Four isocaloric diets ranging in digestible energy (DE) from 21.2% (diet A), 14.8% (B), 8.4% (C), to 3.9% (D) for starch, and 7.2% DE (diet A), 9.9% (B), to 12.7% DE (diet C and D) for fat were fed for 6-week periods (4 weeks with exercise) using a 4 X 4 Latin square design. Postprandial glucose and insulin responses were measured, and 4 hours postexercise, serum CK activity, glucose, insulin, free fatty acids (FFA), and beta-hydroxybutyrate (beta-HBA) were analyzed. Glycogen, glucose-6-phosphate, citrate synthase, 3-hydroxy-acyl-CoA dehydrogenase, lactate dehydrogenase as well as abnormal polysaccharide and lipid content were measured in middle gluteal muscle samples. Postprandial insulin and glucose response was higher for diet A versus D. Log CK activity was higher with diets A, B, and C versus D. Daily insulin was higher and FFA lower on diet A versus B, C, and D, whereas glucose varied only slightly with diet. Muscle oxidative capacity and lipid stores were low in PSSM horses and muscle glycogen and abnormal polysaccharide content high on both diets A and D. Individual variation occurred in the response of PSSM horses to diets differing in starch and fat content. However, for those horses with clinical manifestations of PSSM, a diet with <5% DE starch and >12% DE fat can reduce exertional rhabdomyolysis, potentially by increasing availability of FFA for muscle metabolism.

Epidemiologic characteristics and management of polysaccharide storage myopathy in Quarter Horses.

To characterize onset and clinical signs of polysaccharide storage myopathy (PSSM) in a well-defined population of affected Quarter Horses, identify risk factors for PSSM, determine compliance of owners to dietary and exercise recommendations, and evaluate the efficacy of dietary and exercise recommendations. 40 Quarter Horses with PSSM and 37 unaffected control horses. Owners of horses with PSSM completed a retrospective questionnaire concerning their horse's condition. Between horses with PSSM and control horses, no significant differences were found in sex distribution (21 vs 15 females and 16 vs 22 males, respectively), temperament, muscle build, diet, or amount of turnout. In horses with PSSM, signs of muscle stiffness, muscle fasciculations, sweating, exercise intolerance, weakness, muscle wasting, reluctance to move, colic, abnormal gait, recumbency, lameness, and swollen muscles began between the age of 1 day and 14 years (mean age, 4.9 +/- 3.5 years). Five horses with PSSM developed acute muscle atrophy. Sixty-three percent (25/40) of owners fed the recommended diet, 55% (22/40) provided regular exercise, and 40% (16/40) followed both dietary and exercise recommendations. Owners of affected horses for which a decrease in severity or frequency of PSSM was not found did not follow the exercise, dietary, or both recommendations. All horses for which both dietary and exercise recommendations were followed had improvement in signs of PSSM. n addition to exertional rhabdomyolysis, signs of PSSM include acute muscle atrophy and gait abnormalities. It appears that PSSM can be managed by following dietary recommendations combined with gradual increases in daily exercise.

Nutritional Support for Rhabdomyolysis

ying-up is a horseman’s descriptive term for exertional rhabdomyolysis (ER). Both terms describe the results of a number of specific muscle pathologies that appear to have a single cause. Recent studies, however, show that there are a number of specific causes of ER, and that information helps to understand why prevention and treatment has been elusive over the years. Many years ago when the condition was first described in draft horses, it was thought that diet had a lot to do with the condition. It occurred in work horses generally on Monday mornings—thus the term “Monday morning disease” was coined. A nutritional prevention plan was devised that was quite successful in many cases. What happened was that horses were worked hard six days a week and kept in their stalls on Sunday (to rest). The same amount of grain was fed Sunday as the rest of the week. Often this grain contained a large amount of molasses. Looking back on the situation, once muscle physiology was better understood, it appeared that the muscle cells were being overloaded with glycogen with no way to utilize it. Cutting the Sunday grain feeding usually helped alleviate the problem. Today we see a different type of ER with the expansion of horse racing and other intense pleasure horse activities. At the recent ACVIM Forum in Charlotte, North Carolina, Dr Stephanie Valberg provided some useful nutritional advice on ER under the catchy title “untying the knots through nutrition.” She emphasized that despite similarities of clinical signs, pathogenesis can vary from case to case. She described the typical ER and other types such as recurrent exertional rhabdomyolysis, sporadic ER, chronic ER, and polysaccharide storage myopathy.

Four cases of equine polysaccharide storage myopathy in the United Kingdom

This paper describes four cases of equine polysaccharide storage myopathy which were confirmed by histological examination of muscle biopsy specimens. The horses were of mixed breeding, with warmblood and thoroughbred...

Polysaccharide storage myopathy in the M longissimuslumborum of showjumpers and dressage horses with back pain.

Australian Veterinary JournalVolume 81, Issue 1-2 p. 95-95 Polysaccharide storage myopathy in the M longissimuslumborum of showjumpers and dressage horses with back pain. First published: 10 March 2008 https://doi.org/10.1111/j.1751-0813.2003.tb11444.xAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinkedInRedditWechat No abstract is available for this article. Volume81, Issue1-2January 2003Pages 95-95 RelatedInformation

Molecular characterization and mutational screening of the PRKAG3 gene in the horse

The PRKAG3 gene encodes a muscle-specific isoform of the regulatory γ subunit of AMP-activated protein kinase (AMPK). A major part of the coding PRKAG3 sequence was isolated from horse muscle cDNA using reverse-transcriptase (RT)-PCR analysis. Horse-specific primers were used to amplify genomic fragments containing 12 exons. Comparative sequence analysis of horse, pig, mouse, human, Fugu, and zebrafish was performed to establish the exon/intron organization of horse PRKAG3 and to study the homology among different isoforms of AMPK γ genes in vertebrates. The results showed conclusively that the three different isoforms (γ1, γ2, and γ3) were established already in bony fishes. Seven single nucleotide polymorphisms (SNPs), five causing amino acid substitutions, were identified in a screening across horse breeds with widely different phenotypes as regards muscle development and intended performance. The screening of a major part of the PRKAG3 coding sequence in a small case/control material of horses affected with polysaccharide storage myopathy did not reveal any mutation that was exclusively associated with this muscle storage disease. The breed comparison revealed several potentially interesting SNPs. One of these (Pro258Leu) occurs at a residue that is highly conserved among AMPK γ genes. In an SNP screening, the variant allele was only found in horse breeds that can be classified as heavy (Belgian) or moderately heavy (North Swedish Trotter, Fjord, and Swedish Warmblood) but not in light horse breeds selected for speed or racing performance (Standardbred, Thoroughbred, and Quarter horse) or in ponies (Icelandic horses and Shetland pony). The results will facilitate future studies of the possible functional significance of PRKAG3 polymorphisms in horses.

Developmental Onset of Polysaccharide Storage Myopathy in 4 Quarter Horse Foals

Developmental Onset of Polysaccharide Storage Myopathy in 4 Quarter Horse Foals

Polysaccharide storage myopathy in the M. longissimus lumborum of showjumpers and dressage horses with back pain.

This study was designed to investigate whether horses with clinical signs of back pain due to suspected soft tissue injuries were affected by polysaccharide storage myopathy (PSSM). Diagnosis of PSSM in muscle biopsies obtained from the M. longissimus lumborum of 5 showjumpers and 4 dressage horses with a history of back pain is reported. M. longissimus lumborum biopsies of these horses were characterised histopathologically and in 3/9 cases also by electron microscopy. Observations were compared with M. gluteus biopsies of the same horses, and with M. gluteus biopsies obtained from 6 Standardbreds with recurrent exertional rhabdomyolysis and from 6 healthy trotters. M. longissimus biopsies from horses with back pain showed pathognomonic signs of PSSM, i.e. high glycogen and/or abnormal complex amylase-resistant polysaccharide deposits. Similar features were found in M. gluteus biopsies of the same horses. Sections of horses with rhabdomyolysis had increased PAS stain when compared with healthy horses, but did not show amylase-resistant material. Qualitative observations were corroborated by quantitative histochemistry (optical densities) of sections stained with PAS and amylase PAS. This study demonstrated the presence of PSSM in the M. longissimus of showjumpers and dressage horses with back pain and indicates that epaxial muscle biopsy is an option in diagnosing back problems in horses when clinical examination and imaging techniques do not provide a precise diagnosis.

Developmental onset of polysaccharide storage myopathy in 4 Quarter Horse foals.

Polysaccharide storage myopathy (PSSM) is characterized by the accumulation of glycogen and an abnormal polysaccharide in the skeletal muscle fibers of Quarter Horse–related breeds. Glycogen storage disorders have been identified in human beings and other animal species that are due to single gene mutations causing deficiencies in the enzyme activities of the glycogenolytic or glycolytic pathways.1 Biochemical studies have demonstrated that horses with PSSM have functional glycogenolytic and glycolytic pathways.2 More recently, muscle glycogen and abnormal polysaccharide accumulation in PSSM horses have been suggested to be due to a novel defect in glucose transport in skeletal muscle. Results of IV and oral glucose tolerance tests in adult PSSM horses indicated that affected individuals have enhanced glucose clearance from the bloodstream, which occurs at lower insulin concentrations than in controls.3 Clinical signs of PSSM include muscle stiffness, pain, and reluctance to exercise and are usually 1st noticed in adult horses at the commencement of training or when exercise resumes after a lay-up period.4 Serum creatine kinase (CK) activity may be high at rest in PSSM horses and can increase up to 80,000 IU/L after a 15-minute submaximal exercise test.5 Although pedigree analysis suggests that PSSM is probably transmitted as an autosomal recessive trait, there is little information about the expression of the disease from birth to the beginning of training at 2–3 years of age.6 Recently, 2 foals with pneumonia developed severe rhabdomyolysis and were diagnosed with PSSM, suggesting that, under certain circumstances, this disorder may be expressed in young animals.7 The purpose of this longitudinal study was to follow the offspring from PSSM mares bred to a closely related stallion to determine the age of onset of skeletal muscle glycogen and abnormal polysaccharide accumulation, enhanced glucose clearance, and exertional rhabdomyolysis that are indicative of PSSM. The