Glycogen synthase 1 (GYS1) mutation in diverse breeds with polysaccharide storage myopathy

Background: A missense mutation in the GYS1 gene was recently described in horses with polysaccharide storage myopathy (PSSM).
Objectives: 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.
Animals: Eight hundred and thirty-one PSSM horses from 36 breeds.
Procedures: Horses with PSSM diagnosed by histopathology of skeletal muscle biopsy samples were identified from the Neuromuscular Disease Laboratory database. Eight hundred and thirty-one cases had blood or tissue that was available for DNA isolation; these 831 cases were genotyped for the GYS1 mutation by restriction fragment length polymorphism.
Results: The PSSM mutation was identified in horses from 17 different breeds. The prevalence of the GYS1 mutation in PSSM horses was high in Draft- (87%) and Quarter Horse-related breeds (72%) and lower in Warmbloods (18%) and other light horse breeds (24%), when diagnosis was based on grade 2 diagnostic criteria. Overall, the PSSM mutation was present in 16% of grade 1 and 70% of grade 2 PSSM horses.
Conclusions and Clinical Importance: GYS1 mutation causes PSSM in diverse breeds and is the predominant form of PSSM in Draft- and Quarter Horse-related breeds. False-positive diagnosis, as well as the possibility of a second glycogenosis in horses with neuromuscular disease (type 2 PSSM), might explain the absence of the GYS1 mutation in horses diagnosed with excessive glycogen accumulation in muscle.     

Hereditary equine regional dermal asthenia (HERDA) in Quarter Horses: A review of clinical signs,genetics and research

Hereditary equine regional dermal asthenia (HERDA) results from a genetic mutation which affects the skin and other tissues of Quarter Horses and horses with Quarter Horse lineage. The disease HERDA has an autosomal recessive mode of inheritance and has become a significant concern in the Quarter Horse industry due to the high frequency of heterozygote carriers. Affected homozygous horses appear normal at birth; however, within the first 2 years of life they usually acquire loose, hyperextensible skin and wounds which result in disfiguring scars either spontaneously or from minor trauma. Some severely affected horses also develop haematomas and seromas. Consequently, most affected horses are subjected to euthanasia at an early age. No treatment options other than palliative therapy currently exist. As part of a five panel test ( http://www.aqha.com/News/News-Articles/2013/April/04292013-Genetic-Testing.aspx ) the American Quarter Horse Association presently requires DNA testing for HERDA on all breeding stallions. There are currently no restrictions on registration of horses heterozygous or homozygous for the HERDA mutation. Due to the autosomal recessive nature of the disease, Quarter Horse mares and horses of all breeds from HERDA‐associated bloodlines should also be tested.     

Neonatal Alloimmune Thrombocytopenia in a Quarter Horse Foal

Neonatal alloimmune thrombocytopenia is recognized as a spontaneous disease of human infants, piglets, and possibly mules, but it has not been previously reported in horses. A 1–day-old Quarter Horse foal presented to Michigan State University Large Animal Clinic with severe thrombocytopenia of unknown origin. Immunoglobulins that bound to the foal's platelets were identified in the mare's plasma, serum, and milk by indirect assays. The immunoglobulins were further shown to recognize platelets from the foal's full brother, born 1 year earlier. These findings, coupled with the clinical course of the foal during its period of hospitalization, strongly suggest that neonatal alloimmune thrombocytopenia can spontaneously occur in neonatal horses. This diagnosis should be considered for foals with severe thrombocytopenia when other causes can be excluded, and platelet antibody assays should be used to support this diagnosis.     

Characteristics of Thoroughbred and Quarter Horse racehorses that sustained a complete scapular fracture

Reasons for performing study: To determine if scapular fractures occur in racehorses with distinctive characteristics. Objectives: To test the hypothesis that Thoroughbred (TB) and Quarter Horse (QH) racehorses with a scapular fracture have similar characteristics that are different from those of their respective racetrack populations. Methods: Necropsy findings, case details, last race information and career earnings for TB and QH racehorses that had a scapular fracture in California between 1990 and 2008 were retrospectively compared between breeds. Horse signalment, career earnings, career starts and race characteristics were obtained for all California racehorses. Comparisons were made between affected horses, other racehorses that died, and all horses that raced, in California during the 19 year period. Results: Seventy‐three TB and 28 QH racehorses had a similar, complete comminuted scapular fracture with an articular component, and right forelimb predilection. The QHs had a higher incidence of scapular fracture incurred during racing than TBs (0.98 vs. 0.39/1000 starters). The TB and QH incident rates for musculoskeletal deaths incurred racing were 20.5 and 17.5/1000 starters, respectively; however, a greater proportion of TB musculoskeletal deaths occurred training (40% vs. 8%). Horses with a scapular fracture were more likely to be male and aged 2 or ≥5 years than the racetrack population. Most affected QHs (64%) were 2‐year‐olds; most TBs (74%) were aged ≥3 years. Scapular fractures occurred more commonly during racing in QHs (70%) than TBs (44%). Race‐related scapular fracture was more likely to occur in a Maiden race than in a non‐Maiden race. Horses with a scapular fracture had fewer career starts than the racetrack population. Conclusions and potential relevance: Despite breed differences for signalment and exercise distances, both breeds incur a complete scapular fracture that is more likely to occur in the right scapula of young and older, male racehorses, early in their race career or after few races. Quarter Horses sustain a catastrophic scapular fracture more frequently than TBs.     

Glycogen branching enzyme deficiency in quarter horse foals

Seven related Quarter Horse foals that died by 7 weeks of age were examined for glycogen branching enzyme (GBE) deficiency. Clinical signs varied from stillbirth, transient flexural limb deformities, seizures, and respiratory or cardiac failure to persistent recumbency. Leukopenia (5 of 5 foals) as well as high serum creatine kinase (CK; 5 of 5), aspartate transaminase (AST; 4 of 4), and gamma glutamyl transferase (GGT; 5 of 5) activities were present in most foals, and intermittent hypoglycemia was present in 2 foals. Gross postmortem lesions were minor, except for pulmonary edema in 2 foals. Muscle, heart, or liver samples from the foals contained abnormal periodic acid Schiff's (PAS)-positive globular or crystalline intracellular inclusions in amounts proportional to the foal's age at death. Accumulation of an unbranched polysaccharide in tissues was suggested by a shift in the iodine absorption spectra of polysaccharide isolated from the liver and muscle of affected foals. Skeletal muscle total polysaccharide concentrations were reduced by 30%, but liver and cardiac muscle glycogen concentrations were normal. Several glycolytic enzyme activities were normal, whereas GBE activity was virtually absent in cardiac and skeletal muscle, as well as in liver and peripheral blood cells of affected foals. GBE activities in peripheral blood cells of dams of affected foals and several of their half-siblings or full siblings were approximately 50% of controls. GBE protein in liver determined by Western blot was markedly reduced to absent in affected foals, and in a half-sibling of an affected foal, it was approximately one-half the amount of normal controls. Pedigree analysis also supported an autosomal recessive mode of inheritance. The affected foals have at least 2,600 half-siblings. Consequently, GBE deficiency may be a common cause of neonatal mortality in Quarter Horses that is obscured by the variety of clinical signs that resemble other equine neonatal diseases.     

Hyperkalaemic periodic paralysis‐like syndrome in a Criollo Argentino horse

Hyperkalaemic periodic paralysis (HYPP) is a relatively new genetic disease that, so far, appears to be confined to descendants of the American Quarter Horse Impressive, a stallion identified as the link between the pedigrees of all affected horses, and that predominantly affects Quarter Horses but also Paint horses, Appaloosas and Palominos. This study suggests that an episode of muscle weakness, which was reported in a Criollo Argentino genetically unrelated to Impressive, was related to marked hyperkalaemia. The symptoms in this case were reproducible following a KCI challenge test although DNA testing for HYPP was negative. Based on these findings, a diagnosis of a HYPP‐like syndrome was made.     

Ultrasonographic Diagnosis of Acute Extrusion of the Lateral Meniscus in a Competing Quarter Horse

A 4-year-old Quarter Horse gelding with a history of acute trauma was presented to our faculty. This report describes the inciting injury, documented in a video, and the ultrasonographic diagnosis of a traumatic extrusion of the right lateral meniscus with an accompanying extra-articular hematoma and distal collateral ligament lesion in a competing Quarter Horse. The ultrasonographic diagnosis of a lateral meniscal injury directly correlated with postmortem findings and this type of lateral meniscal injury has not been previously described in detail.     

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.     

The use and efficacy of horse blood typing tests

Horse blood typing, an assay of red blood cell and serumgenetic markers, is a useful tool for horse breeders and horse registries. It has applications to veterinary Tnedicine as well. For recognizing incorrect paternity (or maternity) a 20-system test battery is calculated to be about 96 percent effective in Thoroughbreds and Arabians and as high as 98 percent in other US breeds such as Standardbreds, Morgans, Quarter Horses, Paso Finos and Peruvian Pasos. In addition to paternity testing, horse blood typing tests can be applied to problems of horseidentification, diagnosis and management of neonatal isoerythrolysis and selection of blood transfusion donors.     

Fatal Myocardial Degeneration in an Adult Quarter Horse with Vitamin E Deficiency

A carcass of an adult female Quarter Horse that spontaneously died was received for general investigation at the veterinary diagnostic laboratory of North Dakota State University. Routine necropsy examination demonstrated multiple pale and firm foci in the heart that were histologically consistent with severe myocardial degeneration/necrosis and fibrosis. Analysis of a liver sample confirmed a suboptimal vitamin E level and a selenium value that was within reference range. Because there was no anamnestic indication for ingestion of cardiotoxic plants or evidence of other etiologic factors, vitamin E deficiency was concluded to have led to the development of the myocardial lesions, which precipitated acute heart failure resulting in sudden death.     

Estimated frequency of the canine hyperuricosuria mutation in different dog breeds

Background: Hyperuricosuria is a condition that predisposes dogs to urate urolithiasis. A mutation that causes canine hyperuricosuria was previously identified in 3 unrelated dog breeds. The occurrence of the mutation in additional breeds was not determined. Hypothesis/Objectives: Identify additional breeds that have the hyperuricosuria mutation and estimate the mutant allele frequency in those breeds. Animals: Three thousand five hundred and thirty dogs from 127 different breeds were screened for the hyperuricosuria mutation. Methods: DNA samples were genotyped by pyrosequencing and allele‐specific polymerase chain reaction methods. Results: Mutant allele frequencies that range from 0.001 to 0.15 were identified in the American Staffordshire Terrier, Australian Shepherd, German Shepherd Dog, Giant Schnauzer, Parson (Jack) Russell Terrier, Labrador Retriever, Large Munsterlander, Pomeranian, South African Boerboel, and Weimaraner breeds. Conclusions and Clinical Importance: The hyperuricosuria mutation has been identified in several unrelated dog breeds. The mutant allele frequencies vary among breeds and can be used to determine an appropriate breeding plan for each breed. A DNA test is available and may be used by breeders to decrease the mutant allele frequency in breeds that carry the mutation. In addition, veterinarians may use the test as a diagnostic tool to identify the cause of urate urolithiasis.     

Bilateral Catastrophic Metacarpal Fractures in a Quarter Horse Gelding

A 5 year-old, 450 kg, American Quarter Horse gelding was presented for postmortem examination. The horse had sustained multiple fractures of the metacarpal bones of both fore limbs while being ridden at a canter. Based on the radiographic presence of parasagittal fractures in the condyles of the distal third metacarpus, we theorized that the fractures in this horse likely originated in the metacarpophalangeal joint and propagated into the diaphysis resulting in catastrophic failure. The unique finding in this case is that these injuries occurred in a horse that was not being trained for racing. Owners and trainers should be aware that horses trained for disciplines other than racing can develop condylar fractures similar to racing Thoroughbreds and Quarter Horses.     

Developmental orthopaedic disease and early osteoarthritis of the temporomandibular joint in a 15-month-old Quarter Horse filly

A 15-month-old Quarter Horse filly presented for evaluation of hard swellings over the left temporomandibular joint (TMJ) and the right metatarsophalangeal joint (MTPJ). The TMJ swelling had been noted since she was weaned at 4 months of age and had slowly enlarged since then. Radiographs of both TMJs and the right MTPJ were performed, which revealed severe osteoarthrosis associated with osteochondrosis-like lesions. The filly was subjected to euthanasia due to the poor prognosis for performance. Computed tomography and post-mortem examination, including histopathology of the left TMJ, revealed early osteoarthritis (OA) associated with osteochondrosis-like lesions of the left TMJ and the right MTPJ, while the right hind proximal interphalangeal joint (PIPJ) was diagnosed with early OA.     

Plasma antithrombin-III values in healthy horses: effect of sex and/or breed

Plasma antithrombin-III (AT-III) values were determined in 74 healthy horses by an automated spectrophotometric assay. The mean plasma AT-III value was 218% +/- 18% of normal human plasma. Plasma AT-III values did not differ significantly (P less than 0.05) among Thoroughbred, Standardbred, Quarter Horse, and other breeds or among mares, geldings, or stallions.     

Bilateral lymphosarcoma of the nictitating membrane in a Quarter Horse

A 21-year-old Quarter Horse mare presented for a mass of the right nictitating membrane. The entire right nictitating membrane was surgically removed and diagnosed as a mixed cell lymphosarcoma and squamous cell carcinoma. The horse had no systemic signs of lymphosarcoma. Approximately 1.5 years later, the horse presented with a similar mass in the left nictitating membrane. The entire left nictitating membrane was surgically removed and diagnosed as a mixed cell lymphosarcoma. In this case, complete surgical removal of the masses resulted in a cure. The horse has remained free of systemic lymphosarcoma for over 3 years.

Case report

A 21-year-old gray Quarter Horse mare was presented to the Kansas State University Veterinary Medical Teaching Hospital for evaluation of a mass involving the right nictitating membrane. The mass was first noticed 5 weeks before presentation and had been treated by the referring veterinarian with a topical steroid solution twice daily. Administration of the topical steroid caused some decrease in the swelling, but it quickly returned once medication was discontinued. The horse had no other medical complaints and appeared to be otherwise healthy. On ocular examination, chemosis of the third eyelid and conjunctiva of the right eye was evident. Direct and indirect pupillary light reflexes, Schirmer tear test, and intraocular pressures were normal in both eyes. Fluorescein stain uptake was negative in both corneas. Cranial nerve and vision examinations did not reveal any abnormalities. On further examination of the right nictitating membrane, a firm mass was palpated under and protruding from the palpebral conjunctiva (Fig 1). No other abnormalities were found on physical examination.     

Computed Tomography and Magnetic Resonance Imaging of an Epidermoid Cyst in a Foot of a Horse

An 18-year-old Quarter Horse mare was evaluated because of moderate left forelimb lameness of 4 weeks’ duration. The clinical evaluation and diagnostic perineural analgesia localized the lameness to the distal portion of the left forelimb. There was swelling on the dorsal and lateral aspect of the coronary band. Radiography, ultrasound, magnetic resonance imaging, and computed tomography of the foot revealed circumscribed well-capsulated soft tissue mass causing a focal deformation of the dorsolateral border of the middle phalanx. The treatment aimed to remove the mass surgically and stabilized the interphalangeal joint, but the owner elected human euthanasia before treatment attempt. Histopathology diagnosis was an epidermoid cyst, which was characterized by multilayers of keratin surrounded by stratified squamous epithelium. Although rare, an epidermoid cyst should be considered as a differential diagnosis for space-occupying mass in horses’ foot that develops chronic lameness after trauma. This report describes the multimodality appearance of the epidermoid cyst.     

Treatment of Coccidioidomycosis Osteomyelitis with ltraconazole in a Horse

Itraconazole, a tricyclic azole effective against a number of deep mycotic diseases, was used to treat a Quarter Horse filly with coccidioidomycosis. The horse was almost normal after 90 days of treatment. Five months after discontinuing itraconazole treatment, the filly had severe neck pain and neurologic signs from recurrence of coccidioidomycosis and was treated with itraconazole for an additional 6 months. Her clinical condition improved to almost normal and the filly has remained normal for 2 years. There was no evidence of drug toxicity.     

Primary Hyperparathyroidism in a Quarter Horse Mare Associated With a Chief Cell Adenoma

Primary hyperparathyroidism is rare in large animal species, and little is known regarding its pathophysiology, endocrine and electrolyte derangements, diagnosis, medical management, and prognosis. This report describes the clinicopathologic diagnosis of a parathyroid (PT) gland chief cell adenoma in a 12-year-old Quarter Horse mare, including PT hormone (PTH) and electrolyte disarrangements associated with the neoplasia, the surgical removal of the adenoma, and medical management of the case. This report also describes for the first time the use PTH immunohistochemistry to confirm the nature of this neoplasia in a horse.     

Growth of Twin Quarter Horses

Equine twins that survive gestation and the first few days postparturition are relatively rare, and growth data for equine twins are missing from the published literature. Documentation of the growth and developmental patterns of equine twins should be helpful in establishing expected rates of growth and in evaluating nutritional and management protocols best suited to equine twins. Weekly body weights were recorded on Quarter Horse twins over a span of approximately 640 days, and both body weights and average daily gain were compared to singleton Quarter Horse foals and standard growth curves. Average daily gain measurements showed a steady increase over the 640-day period, suggesting that the twins were undergoing catch-up growth. It is of particular note; although not surprising, that the twins do not follow any of the predicted growth curves. The frequency of measurements allow for a high-resolution perspective on short-term changes in the rate of gain and highlight the potential for further research on the normal patterns of equine growth. The data presented here are a unique study of the early growth pattern of equine twins.     

The use of computed tomography in the diagnosis of an ectopic ureter in a Quarter Horse filly

This report describes a 4‐month‐old Quarter Horse filly with an ectopic ureter. The filly presented with signs of urinary incontinence, which had been present since birth. Computed tomography (CT) examination and cystoscopy confirmed a diagnosis of a unilateral ectopic ureter. A nephrectomy of the left kidney was performed and renal function was closely monitored post operatively. The filly was treated for abdominal chylous effusion as a post operative complication. The filly survived to discharge from the hospital, and maintained normal urinary function at 12 months post operatively.