Polysaccharide Storage Myopathy (PSSM) is a hereditary muscle disorder affecting horses, characterized by the abnormal accumulation of glycogen and polysaccharides in skeletal muscle tissue. This condition can lead to muscle stiffness, weakness, and pain, particularly after exercise. PSSM is primarily associated with specific genetic mutations that affect glycogen synthesis and storage. Horses with PSSM may exhibit symptoms such as reluctance to move, sweating, and muscle tremors. Diagnosis typically involves muscle biopsy and genetic testing. This page compiles peer-reviewed research studies and scholarly articles that explore the genetic basis, pathophysiology, and management strategies for Polysaccharide Storage Myopathy in equine populations.
McKenzie EC, Firshman AM.Chronic exertional rhabdomyolysis represents a syndrome of recurrent exercise-associated muscle damage in horses that arises from a variety of etiologies. Major advances have been made in the understanding of the pathophysiology of this disease, and causative genetic defects have been recently identified for two conditions-polysaccharide storage myopathy of quarter horses, paints, warm bloods, and draft breeds. Dietary management in combination with a regular exercise regimen comprises the most effective means for control of clinical signs.
McCue ME, Valberg SJ, Jackson M, Borgia L, Lucio M, Mickelson JR.In this study we examined a family of Quarter Horses with Polysaccharide Storage Myopathy (PSSM) with a dominant mutation in the skeletal muscle glycogen synthase (GYS1) gene. A subset of horses within this family had a more severe and occasionally fatal PSSM phenotype. The purpose of this study was to identify a modifying gene(s) for the severe clinical phenotype. A genetic association analysis was used to identify RYR1 as a candidate modifying gene. A rare, known equine RYR1 mutation, associated with malignant hyperthermia (MH), was found to segregate in this GYS1 PSSM family. Retrospective ...
Herszberg B, McCue ME, Larcher T, Mata X, Vaiman A, Chaffaux S, Chérel Y, Valberg SJ, Mickelson JR, Guérin G.Glycogen storage diseases or glycogenoses are inherited diseases caused by abnormalities of enzymes that regulate the synthesis or degradation of glycogen. Deleterious mutations in many genes of the glyco(geno)lytic or the glycogenesis pathways can potentially cause a glycogenosis, and currently mutations in fourteen different genes are known to cause animal or human glycogenoses, resulting in myopathies and/or hepatic disorders. The genetic bases of two forms of glycogenosis are currently known in horses. A fatal neonatal polysystemic type IV glycogenosis, inherited recessively in affected Qu...
Vinogradov E, MacLean LL, Brooks BW, Lutze-Wallace C, Perry MB.Taylorella equigenitalis is a Gram-negative bacterium that causes venereally transmitted contagious equine metritis (CEM), and its identification and differentiation from other bacteria and Taylorella species is an important requirement for the control of CEM infection. Based on the results of NMR and MS analysis, the antigenic O-polysaccharide (O-PS) component of the lipopolysaccharide (LPS) produced by the type strain T. equigenitalis (ATCC 35865) was found to be a linear polymer composed of a repeating disaccharide unit, containing partially amidated 2,3-diacetamido-2,3-dideoxy-alpha-L-gulu...
McCue ME, Valberg SJ, Lucio M, Mickelson JR.A missense mutation in the GYS1 gene was recently described in horses with polysaccharide storage myopathy (PSSM). Objective: The first objective was to determine the prevalence of the GYS1 mutation in horses with PSSM from diverse breeds. The second objective was to determine if the prevalence of the GYS1 mutation differed between horses diagnosed with PSSM based on grade 1 (typically amylase-sensitive) or grade 2 (typically amylase-resistant) polysaccharide. Methods: Eight hundred and thirty-one PSSM horses from 36 breeds. Methods: Horses with PSSM diagnosed by histopathology of skeletal mus...
Firshman AM, Valberg SJ, Baird JD, Hunt L, DiMauro S.To determine insulin sensitivity, proportions of muscle fiber types, and activities of glycogenolytic and glycolytic enzymes in Belgians with and without polysaccharide storage myopathy (PSSM). Methods: 10 Quarter Horses (QHs) and 103 Belgians in which PSSM status had been determined. Methods: To determine insulin sensitivity, a hyperinsulinemic euglycemic clamp (HEC) technique was used in 5 Belgians with PSSM and 5 Belgians without PSSM. Insulin was infused i.v. at 3 mU/min/kg for 3 hours, and concentrations of blood glucose and plasma insulin were determined throughout. An i.v. infusion of g...
Finno CJ, Spier SJ, Valberg SJ.The recent development of equine genome maps by the equine genome community and the complete sequencing of the horse genome performed at the Broad Institute have accelerated the pace of genetic discovery. This review focuses on genetic diseases in the horse for which a mutation is currently known, including hyperkalemic periodic paralysis, severe combined immunodeficiency, overo lethal white syndrome, junctional epidermolysis bullosa, glycogen branching enzyme deficiency, malignant hyperthermia, hereditary equine regional dermal asthenia, and polysaccharide storage myopathy. Emphasis is placed...
Larcher T, Herszberg B, Molon-Noblot S, Guigand L, Chaffaux S, Guerin G, Cherel Y.Gluteus medius muscle was sampled from 53 Cob Normand horses for histologic evaluation. Twenty horses (38%) exhibited amylase-resistant material in myocytes consistent with polysaccharide storage myopathy. Diameter of affected type II fibers was increased (67.7 +/- 21.4 microm) compared with normal ones (57.3 +/- 19.7 microm). Two groups were distinguished by quantitative study. The first group (n = 14; 26%) was characterized by a low percentage of fibers (m = 0.98%) containing aggregates occurring singly or in perifascicular clusters without myopathic changes. The second group (n = 6; 11%) wa...
Aleman M.Muscle disorders are a common cause of disability in horses. For many years, clinical manifestations such as muscle pain, exercise intolerance, weakness, and stiffness were believed to be caused by a single syndrome. However, in the past years a broad spectrum of muscle disorders have been recognized including glycogen and polysaccharide storage myopathies, malignant hyperthermia, mitochondrial myopathy, hyperkalemic periodic paralysis and others. For some, a specific mutation has been identified. Recognition of the myopathic clinical phenotype and thorough clinical, electrodiagnostic, and his...
McGowan CM, McGowan TW, Patterson-Kane JC.The aim of this study was to determine the prevalence of equine polysaccharide storage myopathy (EPSM) in two populations of horses in the UK. Biopsy specimens from 94 horses presented to an abattoir (population 1), and 46 horses with neuromuscular disorders presented to a university referral hospital (population 2) were obtained over a period of 4years. Histological sections were examined by a veterinary pathologist for lesions including abnormal polysaccharide inclusions in myofibres. In population 1, a diagnosis of EPSM was made in 8% and non-specific myopathy in 33% of horses. In populatio...
McCue ME, Valberg SJ, Miller MB, Wade C, DiMauro S, Akman HO, Mickelson JR.Polysaccharide storage myopathy (PSSM) is a novel glycogenosis in horses characterized by abnormal glycogen accumulation in skeletal muscle and muscle damage with exertion. It is unlike glycogen storage diseases resulting from known defects in glycogenolysis, glycolysis, and glycogen synthesis that have been described in humans and domestic animals. A genome-wide association identified GYS1, encoding skeletal muscle glycogen synthase (GS), as a candidate gene for PSSM. DNA sequence analysis revealed a mutation resulting in an arginine-to-histidine substitution in a highly conserved region of G...
Hunt LM, Valberg SJ, Steffenhagen K, McCue ME.There are few detailed reports describing muscular disorders in Warmblood horses. Objective: To determine the types of muscular disorders that occur in Warmblood horses, along with presenting clinical signs, associated risk factors and response to diet and exercise recommendations, and to compare these characteristics between horses diagnosed with polysaccharide storage myopathy (PSSM), those diagnosed with a neuromuscular disorder other than PSSM (non-PSSM) and control horses. Methods: Subject details, muscle biopsy diagnosis and clinical history were compiled for Warmblood horses identified ...
Firshman AM, Valberg SJ.Insulin resistance is thought to be involved in the pathogenesis of many equine conditions such as pars intermedia dysfunction, equine metabolic syndrome, diabetes mellitus, hyperlipaemia, laminitis, endotoxaemia and osteochondrosis dissecans (OCD); whereas polysaccharide storage myopathy in Quarter Horses and equine motor neuron disease (EMD) have been associated with increased insulin sensitivity. However, it is clear that there is not one ideal test, in terms of both practicality and accuracy, for evaluating insulin sensitivity in horses and improved diagnostic techniques are required. This...
Dranchak PK, Leiper FC, Valberg SJ, Piercy RJ, Carling D, McCue ME, Mickelson JR.To evaluate whether biochemical or genetic alterations in AMP-activated protein kinase (AMPK) play a role in the development of polysaccharide storage myopathy (PSSM) in Quarter Horses. Methods: 30 PSSM-affected and 30 unaffected (control) Quarter Horses. Methods: By use of an established peptide phosphotransfer assay, basal and maximal AMPK activities were measured in muscle biopsy samples obtained from 6 PSSM-affected and 6 control horses. In 24 PSSM-affected and 24 control horses, microsatellite markers identified from the chromosomal locations of all 7 AMPK subunit genes were genotyped wit...
McCue ME, Valberg SJ.To estimate the prevalence of polysaccharide storage myopathy (PSSM) among Quarter Horses in the United States and evaluate possible relationships between muscle glycogen concentration, turnout time, and exercise level. Methods: Cross-sectional study. Methods: 164 overtly healthy Quarter Horses > 2 years old from 5 states. Methods: Horses with a history of exertional rhabdomyolysis or any other muscular disease were excluded. Muscle biopsy specimens were examined histologically for evidence of PSSM and were submitted for determination of muscle glycogen concentration. A diagnosis of PSSM wa...
McCue ME, Ribeiro WP, Valberg SJ.Controversy exists as to the prevalence of polysaccharide storage myopathy (PSSM) in breeds of horses and its impact on performance. Objective: To determine 1) the prevalence of PSSM in horses that presented with a neuromuscular disorder, as well as breed, sex and age distributions and clinical signs 2) effect of diagnostic criteria on prevalence, breed distribution and age of horses diagnosed with PSSM. Methods: Fresh frozen biopsies (n = 1426) submitted to the Neuromuscular Diagnostic Laboratory at the University of Minnesota were searched to identify horses diagnosed with PSSM. Horses with ...
Zeyner A, Hoffmeister C, Einspanier A, Gottschalk J, Lengwenat O, Illies M.Quarter Horses are particularly susceptible to polysaccharide storage myopathy (PSSM). Nutritional therapy and possibly prophylaxis includes fat-supplemented diets whilst starch supply should be kept to a minimum. Objective: To investigate the glycaemic and insulinaemic response of clinically normal Quarter Horses to concentrates high in fat and low in starch. Methods: Twelve Quarter Horses were studied. The precondition for inclusion in the study population was that the horses had not shown clinical signs of myopathy. The Quarter Horses were fed according to a 4 x 4 Latin square design haylag...
Bröjer JT, Essén-Gustavsson B, Annandale EJ, Valberg SJ.To determine concentrations of proglycogen (PG), macroglycogen (MG), glucose, and glucose-6-phosphate (G-6-P) in skeletal muscle of horses with polysaccharide storage myopathy (PSSM) before and after performing light submaximal exercise. Methods: 6 horses with PSSM and 4 control horses. Methods: Horses with PSSM completed repeated intervals of 2 minutes of walking followed by 2 minutes of trotting on a treadmill until muscle cramping developed. Four untrained control horses performed a similar exercise test for up to 20 minutes. Serum creatine kinase (CK) activity was measured before and 4 hou...
Valentine BA, Cooper BJ.Muscle samples from 24 horses with polysaccharide storage myopathy were stained with periodic acid-Schiff (PAS) stain and were immunostained for ubiquitin. Abnormalities detected with PAS stain were coarse granular cytoplasmic aggregates of amylase sensitive glycogen, subsarcolemmal aggregates of glycogen, central amylase sensitive bodies, and a variety of subsarcolemmal to intracytoplasmic amylase resistant polyglucosan inclusions. All amylase resistant inclusions were positive for ubiquitin. Ubiquitin was also detected in many amylase sensitive inclusions. Based on morphologic findings and p...
Valentine BA, Flint TH, Fischer KA.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 ...
Firshman AM, Valberg SJ, Bender JB, Annandale EJ, Hayden DW.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 ...
Firshman AM, Baird JD, Valberg SJ.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. Methods: Prospective cohort study. Methods: 103 BDHs > 1 year old. Methods: 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 ...
Valentine BA, Cooper BJ.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...
Firshman AM, Valberg SJ, Karges TL, Benedict LE, Annandale EJ, Seaquist ER.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). Methods: 4 adult Quarter Horses with PSSM. Methods: 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...
Annandale EJ, Valberg SJ, Essen-Gustavsson B.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. Methods: 7 horses with PSSM and 4 control horses. Methods: 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 dehydrog...
Baird JD, Valberg SJ, Anderson SM, McCue ME, Mickelson JR.The purpose of this study was to determine which continental European draught horse breeds harbour a mutation in the glycogen synthase 1 gene (GYS1) that is known to be responsible for type 1 polysaccharide storage myopathy in quarter horses and North American draught horses. Of a non-random selection of continental European draught horses belonging to 13 breeds, 62 per cent (250 of 403) tested were found to carry the mutant allele. The horses were located in Belgium, France, Germany, The Netherlands, Spain and Sweden. The mutation was identified in animals from each of the breeds examined. In...
Valberg SJ, Geyer C, Sorum SA, Cardinet GH.To trace pedigrees from affected horses, identify likely contributing founder horses, and determine the conditional probability of founder genotypes. Methods: Muscle biopsy records from the Neuromuscular Disease Laboratory at the University of California-Davis and the University of Minnesota were searched to identify horses with a polysaccharide storage myopathy and exercise intolerance/rhabdomyolysis. Pedigrees containing 5 to 6 generations were obtained where possible. Methods: 13 Quarter Horses, 4 American Paint Horses, 3 Appaloosas, and 3 Quarter Horse crossbreds (16 mares, 4 geldings, and...
Firshman AM, Baird JD, Valberg SJ.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. Methods: Prospective cohort study. Methods: 103 BDHs > 1 year old. Methods: 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 ...
Todhunter RJ, Yeager AE, Freeman KP, Parente EJ, Lust G.Keratan sulfate (KS) is a glycosaminoglycan, distribution of which is confined mostly to hyaline cartilage. As such, it is a putative marker of hyaline cartilage catabolism. In experiment 1, a focal osteochondral defect was made arthroscopically in 1 radial carpal bone of 2 ponies, and in 2 other ponies, chymopapain was injected into the radiocarpal joint to induce cartilage catabolism. Sequential and concurrent plasma and synovial fluid concentrations of KS were measured, up to 13 months after induction of cartilage injury, to determine whether changes in KS concentrations reflected cartilage...
Dranchak PK, Leiper FC, Valberg SJ, Piercy RJ, Carling D, McCue ME, Mickelson JR.To evaluate whether biochemical or genetic alterations in AMP-activated protein kinase (AMPK) play a role in the development of polysaccharide storage myopathy (PSSM) in Quarter Horses. Methods: 30 PSSM-affected and 30 unaffected (control) Quarter Horses. Methods: By use of an established peptide phosphotransfer assay, basal and maximal AMPK activities were measured in muscle biopsy samples obtained from 6 PSSM-affected and 6 control horses. In 24 PSSM-affected and 24 control horses, microsatellite markers identified from the chromosomal locations of all 7 AMPK subunit genes were genotyped wit...
Turner TA.Navicular syndrome can be treated in a variety of ways. This is related to the fact that it has a variety of causes. Prognostically, most horses will improve with treatment. One can expect about 50 per cent of the horses to become useably sound for 1 year, no matter what treatment is used. The disease is progressive, and affected horses eventually will need to be retired because of lameness. The author's therapeutic approach is to utilize shoeing as the primary therapy. Shoeing is performed to correct structural problems and to ensure that shoeing is physiologically sound. Nonsteroidal anti-in...
Lentz LR, Valberg SJ, Mickelson JR, Gallant EM.To determine whether increased sensitivity to pharmacologic agents was a general property of equine exertional myopathies, including polysaccharide storage myopathy (PSSM) in Quarter Horses. Methods: 5 adult Quarter Horses with exertional rhabdomyolysis and abnormal polysaccharide accumulation in skeletal muscle and 4 clinically normal adult Quarter or Quarter-type horses. Methods: Twitch time course measurements and contracture responses to various concentrations of caffeine and halothane for small bundles of intact external intercostal muscle fibers were measured in all horses. Results: Caff...
Firshman AM, Valberg SJ, Bender JB, Annandale EJ, Hayden DW.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 ...
Valentine BA, Cooper BJ.Muscle samples from 24 horses with polysaccharide storage myopathy were stained with periodic acid-Schiff (PAS) stain and were immunostained for ubiquitin. Abnormalities detected with PAS stain were coarse granular cytoplasmic aggregates of amylase sensitive glycogen, subsarcolemmal aggregates of glycogen, central amylase sensitive bodies, and a variety of subsarcolemmal to intracytoplasmic amylase resistant polyglucosan inclusions. All amylase resistant inclusions were positive for ubiquitin. Ubiquitin was also detected in many amylase sensitive inclusions. Based on morphologic findings and p...
Valberg SJ, Townsend D, Mickelson JR.To determine whether polysaccharide storage myopathy (PSSM) in Quarter Horses is attributable to a defect in glycolysis or in the allosteric regulation of phosphofructokinase (PFK) enzyme. Methods: Muscle biopsy specimens were obtained from 6 Quarter Horses with PSSM and 8 Quarter Horse or Thoroughbred control horses. Methods: Maximal activity of glycogenolytic and glycolytic enzymes was determined spectrophotometrically. Maximal activity of PFK was determined for each horse at pH 8.0, and at pH 7.0 when variable concentrations of the activators, fructose 6 phosphate, fructose 2,6 bisphosphate...
Valentine BA, de Lahunta A, Divers TJ, Ducharme NG, Orcutt RS.Two Belgian geldings, 4 and 14 years old, respectively, with muscle atrophy, weakness, and abnormal gait characteristic of severe advanced shivers were examined clinically and on necropsy. Neurologic examination revealed no evidence of ataxia, and the clinical diagnosis was neuromuscular weakness and shivers. Necropsies of both horses, including examination of pituitary, brain, spinal cord, spinal roots and ganglia, and peripheral nerves, revealed no gross or histologic abnormalities. Examination of multiple skeletal muscle specimens revealed chronic myopathic changes and periodic acid-Schiff ...
McCue ME, Valberg SJ.To estimate the prevalence of polysaccharide storage myopathy (PSSM) among Quarter Horses in the United States and evaluate possible relationships between muscle glycogen concentration, turnout time, and exercise level. Methods: Cross-sectional study. Methods: 164 overtly healthy Quarter Horses > 2 years old from 5 states. Methods: Horses with a history of exertional rhabdomyolysis or any other muscular disease were excluded. Muscle biopsy specimens were examined histologically for evidence of PSSM and were submitted for determination of muscle glycogen concentration. A diagnosis of PSSM wa...
Annandale EJ, Valberg SJ, Essen-Gustavsson B.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. Methods: 7 horses with PSSM and 4 control horses. Methods: 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 dehydrog...
Schwarz B, Ertl R, Zimmer S, Netzmann Y, Klein D, Schwendenwein I, Hoven RV.The aim of this study was to determine the occurrence and frequency of a mutation in the gene coding for skeletal muscle glycogen synthase type 1 (GYS-1), which is the cause of equine polysaccharide storage myopathy (PSSM) type 1 in a population of 50 Haflingers. GYS-1 genotyping of 50 Haflingers was performed with a validated restriction fragment length polymorphism (RFLP) assay. The second aim was to compare resting and post-exercise muscle enzyme activities as well as parameters of glucose metabolism in blood between horses with and without the mutation. Nine of the 50 Haflingers were ident...
De La Corte FD, Valberg SJ, MacLeay JM, Williamson SE, Mickelson JR.To determine whether excessive glycogen accumulation in skeletal muscle of Quarter Horses with polysaccharide storage myopathy (PSSM) is a result of enhanced cellular uptake of glucose. Methods: 6 horses with PSSM and 10 healthy (control) horses. Methods: Intravenous glucose tolerance tests (IVGTT), oral glucose tolerance tests (OGTT), and modified insulin tolerance tests (MITT) were performed. Plasma glucose and insulin concentrations were measured in blood samples collected before and for up to 8 hours after glucose or insulin administration. Results: Peak glucose concentrations during IVGTT...
Herszberg B, McCue ME, Larcher T, Mata X, Vaiman A, Chaffaux S, Chérel Y, Valberg SJ, Mickelson JR, Guérin G.Glycogen storage diseases or glycogenoses are inherited diseases caused by abnormalities of enzymes that regulate the synthesis or degradation of glycogen. Deleterious mutations in many genes of the glyco(geno)lytic or the glycogenesis pathways can potentially cause a glycogenosis, and currently mutations in fourteen different genes are known to cause animal or human glycogenoses, resulting in myopathies and/or hepatic disorders. The genetic bases of two forms of glycogenosis are currently known in horses. A fatal neonatal polysystemic type IV glycogenosis, inherited recessively in affected Qu...
Escherichia coli F17 isolated from horse feces was studied in respect to the O antigen (O polysaccharide) structure and genetics. The lipopolysaccharide was isolated by phenol-water extraction of bacterial cells and cleaved by mild acid hydrolysis to yield the O polysaccharide, which was studied by sugar analysis and selective solvolysis with CFCOH along with one- and two-dimensional H and C NMR spectroscopy. The O polysaccharide was found to have a branched pentasaccharide repeat (O-unit) containing one residue each of d-galactose, d-mannose, l-rhamnose, d-glucuronic acid, and N-acetyl-d-gluc...
Firshman AM, Valberg SJ, Karges TL, Benedict LE, Annandale EJ, Seaquist ER.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). Methods: 4 adult Quarter Horses with PSSM. Methods: 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...
Valberg SJ, Henry ML, Herrick KL, Velez-Irizarry D, Finno CJ, Petersen JL.Genetic tests for variants in MYOT (P2; rs1138656462), FLNC (P3a; rs1139799323 or P3b; rs1142918816) and MYOZ3 (P4; rs1142544043) genes are offered commercially to diagnose myofibrillar myopathy (MFM) and type 2 polysaccharide storage myopathy (PSSM2) in Quarter Horses (QH). Objective: To determine if PSSM2-QH has histopathological features of MFM. To compare genotype and allele frequencies of variants P2, P3, P4 between control-QH and PSSM2-QH diagnosed by histopathology. Methods: Retrospective cross-sectional. Methods: The study includes a total of 229 healthy control-QH, 163 PSSM2-QH GYS1 ...
Williams ZJ, Bertels M, Valberg SJ.Type 1 polysaccharide storage myopathy (PSSM1) is a glycogen storage disorder of known cause whereas the basis for type 2 PSSM (PSSM2) is unknown. The same diet and exercise regime prescribed for PSSM1 is recommended for PSSM2; however, the benefit of these recommendations for PSSM2 is undocumented. The objectives of this study were to determine traits of PSSM2 Warmblood horses (WB), determine the changes in exercise responses that occur with a recommended low-starch/fat-supplemented diet and exercise regime, and determine if glycogen concentrations correspond to the severity of signs. Owners ...
Valentine BA, Habecker PL, Patterson JS, Njaa BL, Shapiro J, Holshuh HJ, Bildfell RJ, Bird KE.Skeletal muscle samples from 38 draft horse-related animals 1-23 years of age were evaluated for evidence of aggregates of glycogen and complex polysaccharide characteristic of equine polysaccharide storage myopathy (EPSSM). Cardiac muscle from 12 of these horses was also examined. Antemortem serum levels of creatine kinase (CK) and aspartate aminotransferase (AST) from 9 horses with EPSSM and 5 horses without EPSSM were compared. Skeletal muscle from 17 horses contained inclusions of periodic acid-Schiff (PAS)-positive, amylase-resistant complex polysaccharide. Similar inclusions were also pr...
Nichols JL, Robinson JS, Hiney KM, Terry R, Ramsey JW.This study investigated equine nutrition knowledge and educational needs of licensed veterinarians in the United States who were exclusively or predominately equine practitioners. It found veterinarians regard their peers as an important resource of nutritional knowledge, ranking ahead of all other sources except a PhD equine nutritionist. Interestingly, only 21% of veterinarians felt good about their knowledge level in equine nutrition after graduating from veterinary school. Although veterinarians in this study reported equine nutrition to be an area of weakness, 75% had not pursued continui...
Choi YH, Penedo MC, Daftari P, Velez IC, Hinrichs K.Preimplantation genetic diagnosis has great potential in the horse, but information on evaluation of equine embryo biopsy samples is limited. Blastocysts were biopsied using a Piezo drill and methods for whole-genome amplification (WGA) investigated. Results for 33 genetic loci were then compared between biopsy samples from in vitro-produced (IVP) and in vivo-recovered (VIV) blastocysts. Under the experimental conditions described, WGA using the Qiagen Repli-g Midi kit was more accurate than that using the Illustra Genomiphi V2 kit (98.2% vs 25.8%, respectively). Using WGA with the Qiagen kit,...
Valentine BA, Credille KM, Lavoie JP, Fatone S, Guard C, Cummings JF, Cooper BJ.A severe myopathy leading to death or euthanasia was identified in 4 Belgian and 4 Percheron draught horses age 2-21 years. Clinical signs ranged from overt weakness and muscle atrophy in 2 horses age 2 and 3 years, to recumbency with inability to rise in 6 horses age 4-21 years. In 5 horses there was mild to severe increases in muscle enzyme levels. Clinical diagnoses included equine motor neuron disease (2 horses), post anaesthetic myopathy (2 horses), exertional myopathy (2 horses), myopathy due to unknown (one horse), and equine protozoal myelitis (one horse). Characteristic histopathology...
Valberg SJ.Clinical signs that are easily referred to spinal muscle pathology include atrophy of epaxial muscles, focal swelling and palpable tenderness, as well as enlarged muscles with increased tone. Less easily recognized signs include rigidity of the spine, shortened stride, hindlimb lameness, and indicators of poor performance. Muscle biopsy is one option in evaluating sore backs and is best used when physical examination and imaging procedures do not reveal a likely diagnosis or when conventional treatments are unsuccessful. Rhabdomyolysis of spinal muscles may be due to nutritional myodegeneratio...
Naylor RJ, Livesey L, Schumacher J, Henke N, Massey C, Brock KV, Fernandez-Fuente M, Piercy RJ.Equine type 1 polysaccharide storage myopathy (PSSM1), a common glycogenosis associated with an R309H founder mutation in the glycogen synthase 1 gene (GYS1), shares pathological features with several human myopathies. In common with related human disorders, the pathogenesis remains unclear in particular, the marked phenotypic variability between affected animals. Given that affected animals accumulate glycogen and alpha-crystalline polysaccharide within their muscles, it is possible that physical disruption associated with the presence of this material could exacerbate the phenotype. The aim ...
Valberg SJ, Finno CJ, Henry ML, Schott M, Velez-Irizarry D, Peng S, McKenzie EC, Petersen JL.Commercial genetic tests for type 2 polysaccharide storage myopathy (PSSM2) and myofibrillar myopathy (MFM) have not been validated by peer-review, and formal regulation of veterinary genetic testing is lacking. Objective: To compare genotype and allele frequencies of commercial test variants (P variants) in MYOT (P2; rs1138656462), FLNC (P3a; rs1139799323), FLNC (P3b; rs1142918816) and MYOZ3 (P4; rs1142544043) between Warmblood (WB) and Arabian (AR) horses diagnosed with PSSM2/MFM by muscle histopathology, and phenotyped breed-matched controls. To quantify variant frequency in public reposi...
McGowan CM, Menzies-Gow NJ, McDiarmid AM, Patterson-Kane JC.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 dominating. They all had recurrent episodes of rhabdomyolysis, indicated by clinical signs and increased plasma levels of muscle enzymes. They were managed conservatively and have continued athletic careers despite their disease.
De La Corte FD, Valberg SJ, Mickelson JR, Hower-Moritz M.Polysaccharide storage myopathy (PSSM) in Quarter Horses (QH) and QH crosses is a glycogen storage disorder in which blood glucose clearance and insulin sensitivity, following an i.v. or oral glucose challenge, are enhanced. Exercise is known also to enhance glucose uptake into skeletal muscle in many animal species. Therefore, the purpose of this study was to compare the effect of exercise on glucose clearance in PSSM and control horses when an oral carbohydrate meal (8 Mcal sweet feed) was fed following either 12 h fasting alone (NEX protocol) or following fasting and a standard exercise pro...
