HYPP: hyperkalemic periodic paralysis in the horse

Hyperkalaemic periodic paralysis(HYPP) is characterized by intermittent episodes of muscular tremor, weakness, and collapse, and is probably caused by abnormal electrolyte transport in the muscle cell membrane. During an episode of HYPP, most animals are severely hyperkalaemic. HYPP is a hereditary disease and occurs only in American Quarter horses or crossbreds. Because these horses are now being imported into the Netherlands, HYPP should be included in the differential diagnosis of horses showing signs of muscle tremor, paresis, or paralysis. The present article reviews the literature on HYPP and describes a case showing typical signs of the disease.     

Hyperkalemic periodic paralysis, plasma lactate and exercise tolerance

The purpose of this, trial was to determine the effect of hyperkalemic periodic paralysis (HYPP) on exercise tolerance in Quarter Horses. Five HYPP affected and five nonaffected horses were matched for age, size, gender and reproductive status. HYPP status was diagnosed by DNA analysis and potassium chloride challenge testing. Plasma lactate concentration and heart rate were used as indicators of work intensity. Serum potassium concentrations were also monitored. Two exercise experiments were conducted, the first being forty-five minutes of slow, aerobic exercise (hacking) and the other being moderate, partially anaerobic exercise (galloping). Post-exercise the horses were cooled out by randomly assigning them to either forty minutes, of standing still or forty minutes of walking. Heart rates of HYPP affected and unaffected horses were not significantly different during exercise or recovery. Plasma lactate concentrations changed slightly following slow exercise and were significantly higher for HYPP affected horses (P=0.01).At the end of exercise, values were 1.4±0.2 mmol/L and 1.0±0.1 mmol/L for HYPP affected and unaffected horses, respectively. Following moderate exercise, plasma lactate concentrations were much greater, and the difference (P<0.001) between affected and unaffected horses was more marked: immediately following exercise concentrations were 10.6±1.8 and 6.2±1.0 mmol/L in affected and unaffected horses, respectively. The higher post-exercise plasma lactate concentrations in affected horses indicates increased anaerobic muscle metabolism. Serum potassium concentrations rose following exercise and significantly higher values were seen in horses that were walked rather than stood still post-exercise.Hyperkalemic periodic paralysis (HYPP) is a dominant autosomal genetic defect occurring in American Quarter Horses and related breeds. ^1–5 The condition is widely geographically distributed and has been estimated to affect 0.4% of all Quarter Horses.⁶ Signs include sporadic attacks of muscle fasciculation, muscle spasm, sweating and weakness. Oral administration of potassium chloride produces a more severe hyperkalemia in HYPP affected horses and induces clinical attacks.¹ Electromyography reveals widespread continuous, spontaneous, muscle contraction.² Some people believe that HYPP affected horses are suitable for riding⁷; others have expressed doubts about the safety of this practice and the exercise tolerance of affected horses. HYPP affected horses have an unstable muscle membrane potential causing random muscle fiber contractions,^2,8 which could antagonize purposeful movement. This, in combination with increases in extracellular potassium concentration occurring during exercise,^9–11 may cause affected horses to stumble or collapse while being ridden, posing a danger to both horse and rider. In HYPP affected people, potassium concentration rises approximately one to two hours after exercise during which time HYPP attacks can occur.^9,10 For these reasons, the exercise tolerance of HYPP affected horses and the effects of exercise on spontaneous HYPP attacks deserves investigation.We standardized the exercise test and chose heart rate and plasma lactate concentrations as indicatoors, of exercise tolerance and energy metabolism.¹² Heart rate is the major determinant of oxygen delivery to muscle and the rate rises with exercise intensity until it reaches a plateau at high velocities.^13,14 Several lines of investigation indicate that plasma lactate concentrations reflect muscle work. Lactate release from resting muscle is minimal but large amounts are released during strenuous exercise.^15–17 Lactate release increases with increasing muscle work.^16,18 During exercise, muscle oxygen consumption increases until eventually a plateau is reached after which no further increase in oxygen consumption in response to increased work loads is possible.¹⁸ At this point the mitochondrial electron chain transport system is operating at its maximal possible rate, energy production can only be supplemented by the use of inefficient anerobic glycolytic metabolism and the muscle starts to release lactate. If the concentrations of plasma lactate are high, the muscles are depending on anaerobic metabolism and are working closer to exhaustion^16,18–21The objectives of this experiment were twofold. One was to determine if HYPP adversely affects exercise performance. The second was to study the effects of cooling out, by either standing still or walking, on serum potassium and plasma lactate concentrations.     

Successful treatment of hyperkalaemic periodic paralysis in a horse during isoflurane anaesthesia

HistoryA 3-year-old, 400 kg, gelding Quarter Horse was presented for investigation of epistaxis.Physical examinationThe horse was bright, alert and responsive with rectal temperature, heart rate and respiration rate within normal limits.ManagementDuring a second general anaesthetic for surgical treatment of guttural pouch mycosis by balloon-tipped catheter occlusion of the right major palatine artery and ligation of the right external carotid artery, signs consistent with hyperkalaemic periodic paralysis (HYPP) were exhibited. These included concurrent hyperkalaemia, hypercapnoea, sinus tachycardia, and muscle fasciculations in the presence of normothermia. Stress associated with an acute haemorrhage pre-operatively, and intra-operative hypercapnoea may have precipitated the episode. There were no signs of HYPP during a general anaesthetic, 1 week earlier, when an initial attempt at surgical treatment of guttural pouch mycosis was performed. Treatment consisted of fluid therapy and administration of calcium gluconate (0.1–0.2 mg kg^?1 minute^?1), dextrose 5% (5 mL kg^?1 hour^?1) and insulin (0.05 IU kg^?1). Treatment resulted in the resolution of clinical signs and an uneventful recovery.Follow-upThe diagnosis of HYPP was confirmed by DNA analysis post-operatively.ConclusionsClinical cases of intra-operative HYPP can present despite a previous history of uneventful general anaesthesia. Rapid diagnosis and treatment can result in the successful management of HYPP. This report documents an unusual presentation of HYPP, a disease that remains present in the Quarter Horse population.     

Genetic-diet interactions in the Hyperkalemic Periodic Paralysis syndrome in Quarter Horses fed varying amounts of potassium: I. Potassium and sodium balance, packed cell volume and plasma potassium and sodium concentrations

Six broodmares that were genetically tested to be heterozygous (H/N) and six broodmares that were tested to be homozygous negative (N/N) for Equine Hyperkalemic Periodic Paralysis (HYPP), that were descendents of the same stallion, were used in a replicated 3×3 Latin square experiment to determine the genetic-diet relationships in the HYPP syndrome.¹ The mares were fed rations consisting of 65% pelleted concentrate and 35% Coastal Bermuda grass hay that provided 1.1 (diet A), 1.9 (diet B) and 2.9% (diet C) potassium. The experimental periods were 14 days long, resulting in 28 meals per period. At meals 1 and 27, blood samples were taken every 30 minutes for 12 hours and every 10 minutes from 2 to 5 hours post-feeding. Total urine and fecal collections were made on the last 4 days of each period.Water, feed and fecal samples were analyzed for sodium and potassium content. Blood was analyzed for packed cell volume (PCV) and plasma potassium (K⁺) and sodium (Na⁺) concentrations.Apparent absorption of potassium was 99.8% across all diets, and potassium was excreted principally in the urine. More potassium was retained when the horses were fed diet B than diets A or C. Apparent absorption of sodium was 99.6% with no difference by diet. Neither potassium nor sodium balances were affected by HYPP status.There was no post-prandial pattern of plasma K⁺ concentration seen when the horses were fed the low potassium diet. When fed the higher potassium diets, they had greater plasma K⁺ values and exhibited a post-prandial peak at 2 to 5 hours after feeding. This peak occurred in all of the horses, meaning that plasma K⁺ cannot be used as a diagnostic aid for the presence of the HYPP mutation. By meal 27, some adaptation had occurred resulting in lower plasma K⁺ values when the horses were fed the higher potassium diets. The horses had increased plasma K⁺ concentrations throughout the post-prandial period while fed diet B compared to diet A, agreeing with the positive potassium balance seen in this experiment. The HYPP H/N horses had lower plasma Na⁺ concentrations in the early post-prandial hours and continuously greater PCV values than the HYPP N/N horses.     

In vitro contractile responses and contracture testing of skeletal muscle from Quarter Horses with exertional rhabdomyolysis.

OBJECTIVE: To determine whether increased sensitivity to pharmacologic agents was a general property of equine exertional myopathies, including polysaccharide storage myopathy (PSSM) in Quarter Horses. ANIMALS: 5 adult Quarter Horses with exertional rhabdomyolysis and abnormal polysaccharide accumulation in skeletal muscle and 4 clinically normal adult Quarter or Quarter-type horses. PROCEDURES: 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: Caffeine contracture threshold of muscles from Quarter Horses with PSSM was not different from that of clinically normal horses (5 mM in both groups). Muscles from horses with PSSM and from clinically normal horses did not have contracture in response to up to 2% halothane. CONCLUSIONS AND CLINICAL RELEVANCE: Results were in contrast to the increased sensitivity to caffeine and halothane for muscles from Thoroughbreds with recurrent exertional rhabdomyolysis (RER). Although clinical signs of muscular stiffness after exercise are similar between Quarter Horses with PSSM and Thoroughbreds with RER, these breeds appear to have 2 distinct myopathies with different pathophysiologic bases. Unlike RER in Thoroughbreds, PSSM in Quarter Horses does not appear to be accompanied by a defect in regulation of muscle contraction.     

Frequency of musculoskeletal injuries and risk factors associated with injuries incurred in Quarter Horses during races.

OBJECTIVE: To determine the frequency and anatomic location of musculoskeletal injuries incurred by Quarter Horses during races and to compare data from injured horses and matched control horses. DESIGN: Matched case-control study. ANIMALS: 97 Quarter Horses that sustained a musculoskeletal injury during races and 291 horses from the same races that were not injured. PROCEDURE: Data examined included racing history, race-entrant characteristics, racing events determined by analysis of videotapes of races, and, when performed, results of prerace physical inspections. Data for injured horses were compared with data for control horses, using conditional logistic regression. RESULTS: Incidence of a catastrophic injury among Quarter Horses during races was approximately 0.8/1,000 race starts, whereas incidence of musculoskeletal injury during racing was approximately 2.2/1,000 race starts. Odds of musculoskeletal injury were approximately 8 times greater among horses assessed to be at increased risk of injury on the basis of results of prerace physical inspection than for horses not considered to be at increased risk of injury. Evidence was lacking that 2-year-old horses were at increased risk of injury or that sex influenced the risk of injury among Quarter Horses during races. CONCLUSIONS AND CLINICAL RELEVANCE: Incidence of racing injury among Quarter Horses appears to be lower than that observed among Thoroughbreds. Regulatory veterinarians can identify horses at increased risk of injury on the basis of prerace physical inspection, indicating that these inspections could be used to reduce the risk of injury during races.     

Hyperkalaemic periodic paralysis in homozygous and heterozygous horses: a co-dominant genetic condition

Historical, clinical and experimental data were collected from 9 horses homozygous for HYPP (H/H). All showed episodes of respiratory stertor, described as a rattling or honking sound, usually within the first week post partum. Five horses had one or more episodes of dysphagia, in 3 horses this was accompanied by drooling and in 3 by weight loss. In comparison, only one of 35 contemporaneous half siblings (of which approximately half would be expected to be of the H/N genotype and half N/N) was observed to have respiratory stertor prior to weaning and none had problems with dysphagia. One mature homozygous stallion was infertile secondary to urospermia. Six homozygous horses died or were subjected to euthanasia; 4 age less than a year, one age 20 months and one age 5 years. The remaining 3 cases were still alive at the end of the study. A comparison of homozygous and heterozygous horses using standardised potassium chloride challenge testing indicated that during attacks homozygotes showed significantly more frequent signs of drooling, prolapse of the third eyelid, respiratory stridor and weakness than heterozygous horses. Homozygotes also had significantly more total abnormalities (including myotonic discharges, high frequency repetitive discharges, and spontaneous activity) on electromyographic examination than heterozygotes. These data imply that HYPP is inherited as a codominant genetic defect, because the homozygotes showed more severe clinical signs of disease than heterozygotes. Homozygous foals would be expected to be produced in 25% of matings in which both parents are heterozygous. Owners and veterinarians should be aware of the risks of this mating.     

Vertical Frontlimb Ground Reaction Forces of Sound and Lame Warmbloods Differ From Those in Quarter Horses

Lameness is a highly prevalent condition in horses and is the principal cause of removal from athletic activity in this species. In evidence-based veterinary medicine studies to evaluate non-setoidal anti-inflammatory drug (NSAID) therapies, force plates are commonly used to objectively assess improvement of lameness. The objective of this study was to determine whether breed differences would influence force plate measurements in sound and lame riding horses. Force plate measurements of lame (n = 20) and sound (n = 18) Warmblood and lame (n = 15) and sound (n = 8) Quarter Horses were compared. Lameness was visually scored using the grade 0–5 American Association of Equine Practitioners (AAEP) lameness scale. Trotting sound Warmbloods loaded their frontlimbs with 118% body weight (BW) and their hindlimbs with 96% BW, whereas Quarter Horses only used 101% BW in the front and 92% BW in the hindlimbs (P < .05). Furthermore, it appeared and was estimated that, at trot, front-limb-lame Warmblood horses showed higher peak vertical force (PVF) values (grade 2: 89% BW; grade 3: 69% BW), than front-limb-lame Quarter Horses with similar lameness scores (grade 2: 78% BW; grade 3: 66% BW). In conclusion, peak vertical forces (PVF expressed in % BW) of either lame or sound horses seem to be influenced by breed differences between Warmblood and Quarter Horse riding horses. Possible conformation and gait differences enabled trotting Quarter Horses to demonstrate lower absolute PVF values than Warmbloods, whereas trotting lame Warmbloods showed a relatively larger decrease in frontlimb loading and thus in PVF than lame Quarter Horses at a trot. Thus, in studies in which objective lameness observations are recorded, breed differences should be taken into account when specific grades of lameness of a group of horses are to be objectively compared with another group.     

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.     

Racing Performance in 72 Racehorses Treated with Prosthetic Laryngoplasty for Laryngeal Hemiplegia

The purpose of this study was to compare racing performance before and after prosthetic laryngoplasty for treatment of laryngeal hemiplegia in inexperienced (horses without at least one start before surgery) and experienced (horses with at least one start before surgery) Thoroughbred and Quarter Horse racehorses. Medical records of 54 Thoroughbred and 18 Quarter Horse racehorses or horses intended for racing treated with prosthetic laryngoplasty and unilateral ventriculectomy for laryngeal hemiplegia were reviewed. Signalment, age at the time of surgery, resting endoscopic grade of laryngeal function, surgical procedure, and type of suture were recorded. Median performance index (PI), earnings, distance, and Beyer speed figure (BSF) per start for three races before and after surgery were compared, and factors associated with improved postsurgical performance were evaluated. Seventy-three percent of horses that had not raced before surgery and 84% of horses that competed in at least one race before surgery were able to return to racing after surgery. Fifty-nine percent and 27% of Thoroughbreds and Quarter Horses, respectively, were able to improve their PI after surgery. Sixty-two percent and 20% of Thoroughbreds and Quarter Horses, respectively, significantly increased their distance after surgery. Additionally, 61% and 66% of racehorses were able to increase their earnings and BSF after surgery, respectively. Horses treated with laryngoplasty and unilateral ventriculectomy have a good prognosis for return to racing. Inexperienced racehorses have a better prognosis for improvement after surgery than do experienced racehorses. Thoroughbred racehorses have a better success rate than Quarter Horse racehorses.     

Long-term outcome of horses with a slab fracture of the central or third tarsal bone treated conservatively: 25 cases (1976-1993)

OBJECTIVE: To determine clinical features of horses with a slab fracture of the central or third tarsal bone and to report outcome of horses in which treatment did not include surgery. DESIGN: Retrospective study. ANIMALS: 25 horses (14 Standardbreds, 6 Thoroughbreds, 5 Quarter Horses). PROCEDURE: Medical records of horses with a slab fracture of the central (n = 9) or third (16) tarsal bone were reviewed. Only horses for which treatment consisted of confinement to a stall were included in this study. Clinical features and radiographic findings were recorded and summarized. Outcome was determined for racing breeds by obtaining official lifetime race results. Outcome for Quarter Horses was determined by phone survey of the owners. RESULTS: 16 (64%) horses had a successful outcome. Ten of 14 (71%) Standardbreds and 2 of 6 Thoroughbreds returned to racing and started at least 5 races after injury. Four of 5 Quarter Horses for which follow-up information was available successfully returned to their previous activity. Sex, age, limb affected, or gait was not associated with final outcome. Percentage of racehorses with central tarsal bone fractures that had a successful outcome (2/7) was significantly less than percentage with third tarsal bone fractures that did (10/13). CONCLUSIONS AND CLINICAL RELEVANCE: Results suggest that enforced rest without surgical fixation can be an effective therapeutic option for horses with a slab fracture of the central or third tarsal bone, even if athletic function is expected.     

Inheritance of hereditary equine regional dermal asthenia in Quarter Horses

OBJECTIVE: To assess heritability and mode of inheritance for hereditary equine regional dermal asthenia (HERDA) in Quarter Horses. ANIMALS: 1,295 horses with Quarter Horse bloodlines, including 58 horses affected with HERDA. PROCEDURE: Horses were classified as affected or unaffected or as undetermined when data were insufficient to assess phenotype. Pedigree data were analyzed to determine the probable mode of inheritance. Heritability was estimated by use of Bayesian statistical methods. RESULTS: Heritability (mean+/-SD) of HERDA was estimated to be 0.38+/-0.13, with both sexes having an equal probability of being affected. Results for evaluation of the pedigrees were consistent with a single Mendelian autosomal recessive mode of inheritance. CONCLUSIONS AND CLINICAL RELEVANCE: HERDA in Quarter Horses is an inherited disease, and affected horses are more likely to produce affected offspring. An autosomal recessive mode of inheritance should be considered by people making breeding decisions involving Quarter Horses when a first-degree relative has been confirmed with HERDA or has produced affected offspring. In addition, breeders whose horses have produced affected offspring can reduce the likelihood of producing affected horses in the future by avoiding inbreeding.     

Clinical features and treatment of renal tubular acidosis in two horses

Two horses were admitted separately for evaluation and treatment of profound hyperchloremic metabolic acidosis without azotemia. One, an 11-year-old Quarter Horse mare, had been depressed and ataxic for 2 days. The other, a 2-year-old Quarter Horse colt, had a 6-week history of depression, anorexia, and weight loss. Both horses responded to fluid and electrolyte therapy, but required daily oral administration of sodium bicarbonate for maintenance. In each case, the diagnosis was renal tubular acidosis.     

Genetic-diet interactions in the Hyperkalemic Periodic Paralysis syndrome in quarter horses fed varying amounts of potassium: IV. Pre-cecal and post-ileal absorption of potassium and sodium

During an experiment to determine the genetic-diet interactions in genetically predisposed Quarter Horses, biphasic symptoms of Hyperkalemic Periodic Paralysis (HYPP) were observed when the HYPP H/N broodmares were fed the higher potassium rations. ¹ The cause of those symptoms was assumed to be: 1) the difference in absorption times of the highly absorbable potassium citrate in the concentrates and the potassium contained in the cells of the grains and hays in the rest of the rations, 2) partial absorption of potassium in the small intestine followed by no absorption from the cecum and further absorption in the large colon or 3) a combination of both of the above explanations. Since previously cannulated ponies were available in this laboratory, an experiment was designed to determine which of those possibilities was the most likely.

Three ponies, weighing an average of 132 kg, with posterior-ileal cannulas were used in a 3×3 Latin square experiment to determine the amounts of potassium and sodium that would be absorbed pre-cecally and post-ilealy. The ponies were fed the same rations as the mares in the previously described experiment (see part I), which provided approximately 1.1, 1.9 and 2.9% potassium by weight as fed. Samples of water, feces, ileal contents and blood were collected. Water, feed, ileal and fecal samples were analyzed for sodium and potassium concentration.

Apparent absorption of potassium prior to the cecum was 97% when the ponies were fed the low potassium diet and 98% when they were fed the higher potassium diets. Three percent and 2% of the potassium was absorbed from the hindgut when the ponies were fed the low potassium diet and the higher potassium diets, respectively. Nine percent and 16% of sodium was absorbed pre-cecally when the ponies were fed the low potassium diet and the higher potassium diets, respectively. Ninety-one and 84% of the sodium was absorbed from the hindgut, when the ponies were fed the low potassium diet and the higher potassium diets, respectively for 99–100% total absorption of both sodium and potassium from all diets.

These results indicate that the potassium from the three diets was absorbed pre-cecally, and that the process took up to nine hours, resulting in bi-phasic HYPP symptoms in the HYPP H/N mares in the companion experiment. This information can be used to better understand the relationship between dietary potassium, plasma K⁺ concentration and HYPP symptoms.     

Prevalence of radiographic changes in yearling and 2-year-old Quarter Horses intended for cutting

Reasons for performing study: There have been many studies that document radiographic findings in young Thoroughbred and Standardbred horses. No such studies have been performed in Quarter Horses. Objective: To describe the prevalence of radiographic changes in the stifles, tarsi, carpi and fetlocks of young Quarter Horses intended for cutting. Methods: Radiographs of yearling and 2‐year‐old Quarter Horses were obtained from a radiograph repository and a private farm. The carpi, tarsi, fetlocks and stifles were evaluated and radiographic changes categorised by type and location. The frequency of changes was calculated and comparisons were made between the 2 age groups. Results: Of 458 included horses, 408 (89.1%) had radiographic changes, most of which were in the tarsi (304, 69.4%) followed by the stifles (202, 44.5%), hind fetlocks (155 of 355, 43.7%), fore fetlocks (131 of 361, 36.3%) and carpi (27 of 342, 7.9%). Of the horses with stifle changes, 188 (93.1%) were in the medial femoral condyle (MFC). There was a significant difference between the age groups for changes on the distal intermediate ridge of the tibia (DIRT), hindlimb middle phalanx (P2) osteophytes and proximal tibial osteophytes. Conclusions: There is a high prevalence of radiographic changes in presale survey radiographs, especially in the stifles and tarsi, of young Quarter Horses intended for cutting. Potential relevance: Veterinarians examining presale radiographs at cutting horse sales should expect a high prevalence of radiographic changes in this population of horses. Work to determine the clinical relevance of these radiographic changes is currently ongoing.     

Hyperkalaemic periodic paralysis in Australian Quarter Horses

SUMMARY Three Quarter Horse stallions and 5 of their 11 tested progeny were diagnosed as affected with the inherited autosomal dominant defect hyperkalaemic periodic paralysis in Victoria in 1992. The diagnoses were based on the appearance of clinical signs and associated increased plasma potassium concentrations in response to oral potassium loading. All affected horses were descendants of the American Quarter Horse Impressive. Indirect evidence indicates that at least 3 other affected Quarter Horse stallions have stood or are standing at stud in Australia. The clinical details of the affected horses are described and the size of the affected population in Australia is discussed.     

Malignant hyperthermia in a horse anesthetized with halothane

Ahealthy, 565-kg, 14-year-old Quarter Horse gelding, negative for equine protozoal myelitis on serum Western blot and for hyperkalemic periodic paralysis (HYPP) by polymerase chain reaction, was selected for use in an electrophysiology study performed under inhalation anesthesia. The study was performed by following the guidelines of an Animal Use and Care Committee Protocol of the University of California at Davis (UCD 8578). Anesthesia was induced with halothane delivered via a face-mask. The horse was intubated 17 minutes later with an orotracheal tube and anesthesia was maintained with halo-thane by using a semiclosed, large-animal breathing circuit. Although muscle relaxation was otherwise good, the horse's ears remained tensed in a caudal direction throughout the study     

Prevalence of the mutation in cyclophilin B (PPIB), a causal candidate gene for HERDA, among Quarter Horses in France

Hereditary equine regional dermal asthenia (HERDA) in Quarter Horses is an inherited degenerative skin disease. Initially reported as hyperelastosis cutis, HERDA has a phenotype of hyperextensible, fragile skin, with secondary seromas, haematomas, ulcers and scarring. It primarily affects the dorsal aspect of the body. An autosomal recessive mode of inheritance is considered likely, with affected horses more at risk to produce affected offspring. A mutation in cyclophilin B (PPIB) as a novel, causal candidate gene for HERDA has been described, and verified as segregating with carriers and affected horses. Screening of control Quarter Horses in the USA has indicated a 3.5% carrier frequency. The prevalence of this mutation among Quarter Horses in France was determined to be 1.6%.     

Malignant Hyperthermia Associated with Ryanodine Receptor 1 (C7360G) Mutation in Quarter Horses

Background: Anesthetic‐induced malignant hyperthermia (MH) has been documented in Quarter Horses with a single point mutation in the ryanodine receptor 1 gene (RyR1) at nucleotide C7360G, generating a R2454G amino acid substitution. However, there have been no reports of nonanesthetic manifestations of MH in horses with the C7360G mutation. Objective: To describe clinical manifestations of Quarter Horses with the C7360G mutation. Animals: Eleven Quarter Horses with the RyR1 C7360G mutation. Methods: This prospective study included horses with suspected MH, undetermined etiology of sudden death, death within hours of onset of rhabdomyolysis, muscle rigidity, stiffness, intermittent sweating, and persistent increases in serum muscle enzyme activities. Whole blood in EDTA and skeletal muscle were processed for genetic and histochemical analysis. Medical records and pedigrees were collected when available. Results: Both anesthetic‐ and non–anesthetic‐associated myopathic manifestations of MH occurred in halter Quarter Horses with mutation of RyR1. The disease is inherited as an autosomal dominant trait. Clinical and laboratory abnormalities were similar in both forms. Rhabdomyolysis was a common finding in both groups of horses. Skeletal muscle histochemical findings were nonspecific and compatible with a noninflammatory myopathic process. Conclusions and Clinical Importance: MH is a potentially fatal disease of Quarter Horses that could be triggered by halogenated anesthetics and other nonanesthetic factors that may include exercise, stress, breeding, illnesses, and concurrent myopathies.     

A Rapid Detection Method for the Ryanodine Receptor 1 (C7360G) Mutation in Quarter Horses

Background: Anesthetic-induced malignant hyperthermia has been documented in Quarter Horses and is caused by a single-point mutation in the ryanodine receptor 1 gene at nucleotide C7360G generating a R2454G amino acid substitution. An accurate, faster molecular test that is less prone to contamination would facilitate screening for the mutation in horses intended for breeding, in those undergoing surgical procedures, and in those with clinical signs compatible with malignant hyperthermia.
Objective: To report a rapid and accurate method for the detection of the ryanodine receptor 1 C7360G mutation.
Animals: Eleven diseased, 10 healthy, and 225 randomly selected Quarter Horses.
Methods: This study included horses with the ryanodine receptor 1 C7360G mutation as detected by gene sequencing. Available genomic and complementary DNA extracted from whole blood, hair or skeletal muscle was used for genetic analysis. Real-time polymerase chain reaction (RT-PCR) melting curve analysis was performed by equine specific primers and 2 hybridization probes (sensor and anchor probes) that contain the site of the mutation. Results from this method were blinded and compared with nucleic acid sequencing for validation.
Results: A rapid genotyping assay with fluorescence resonance energy transfer probes and melting curve analysis was accurate (100% agreement, K = 1) for identification of affected horses. The prevalence of the mutation in a random population of Quarter Horses was 1.3%.
Conclusions and Clinical Importance: Malignant hyperthermia in Quarter Horses can be rapidly and accurately detected by RT-PCR melting curve genotyping with hybridization probes.