Allele frequency and likely impact of the glycogen branching enzyme deficiency gene in Quarter Horse and Paint Horse populations

Glycogen Branching Enzyme Deficiency (GBED), a fatal condition recently identified in fetuses and neonatal foals of the Quarter Horse and Paint Horse lineages, is caused by a nonsense mutation in codon 34 of the GBE1 gene, which prevents the synthesis of a functional GBE protein and severely disrupts glycogen metabolism. The aims of this project were to determine the mutant GBE1 allele frequency in random samples from the major relevant horse breeds, as well as the frequency with which GBED is associated with abortion and early neonatal death using the tissue archives from veterinary diagnostic laboratories. The mutant GBE1 allele frequency in registered Quarter Horse, Paint Horse, and Thoroughbred populations was 0.041, 0.036, and 0.000, respectively. Approximately 2.5% of fetal and early neonatal deaths in Quarter Horse-related breeds submitted to 2 different US diagnostic laboratories were homozygous for the mutant GBE1 allele, with the majority of these being abortions. Retrospective histopathology of the homozygotes detected periodic acid Schiff's (PAS)-positive inclusions in the cardiac or skeletal muscle, which is characteristic of GBED, in 8 out of the 9 cases. Pedigree and genotype analyses supported the hypothesis that GBED is inherited as a simple recessive trait from a single founder. The frequency with which GBED is associated with abortion and neonatal mortality in Quarter Horse-related breeds makes the DNA-based test valuable in determining specific diagnoses and designing matings that avoid conception of a GBED foal.     

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.     

Studies on serum selenium and tocopherol in white muscle disease of foal

In order to clarify the cause of white muscle disease (W.M.D.) in foals, tocopherol and selenium concentrations in serum and glutathione peroxidase activities in blood were measured. Examination was made on the samples from horses affected with W.M.D., the foal kept with them in the same stable, the foals kept in the stables without affected foals, and respective mares. The heavy-breed horses in Fukuoka prefecture and Tokachi district were also examined for comparison. Serum tocopherol levels of these foals were normal because after intake of colostrum. Mares of affected foals showed lower tocopherol levels than other examined mares (p less than 0.01). Serum selenium levels of all foals were below 65 ppb, showing deficient levels. The mares of affected foals had lower selenium levels than other mares (p less than 0.01). There was a good correlation between serum selenium concentration and blood glutathione peroxidase activity (r = 0.81). Selenium levels in the liver of affected foals were lower than the foals which succumbed with other diseases. Diet supplied in the stables with affected foals showed low alpha-tocopherol and selenium contents. These findings suggest that W.M.D. in foals is attributed to nutritional muscular dystrophy caused by tocopherol and selenium deficiency of their mares in late gestation period.     

MAGNETIC RESONANCE IMAGING OF THE BRAIN OF NORMAL NEONATAL FOALS

Magnetic resonance imaging (MRI) was performed on gthe brain of 5 normal, anesthetized, neonatal (age 3-to-6 days) Quarter Horse foals. The objectives of the study were to develop a technique for imaging the brain of neonatal foals, and to ascertain their normal brain anatomy. Interavenous propofol was administered for induction and maintenance of general anesthesia. Using spin echo MR techniques, T1 weighted sagittal and transverse views, and spin density and T2 weighted transverse views were successfully made of each foal. MR images provided excellent visualization of many anatomic struictures of the brain and head. MRI of the bgrain is feasible for selected neonantal equine patients.     

Estimated prevalence of polysaccharide storage myopathy among overtly healthy Quarter Horses in the United States

OBJECTIVE: 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. DESIGN: Cross-sectional study. ANIMALS: 164 overtly healthy Quarter Horses > 2 years old from 5 states. PROCEDURES: 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 was made if amylase-resistant inclusions that stained with periodic acid-Schiff stain were detected. RESULTS: Prevalences of PSSM on the 2 farms with a history of PSSM were 20% (1/5) and 40.7% (11/27); mean prevalence for the other 4 farms was 6.1% (8/132). Sex was not significantly associated with a diagnosis of PSSM, and age was not significantly different between horses with and without PSSM. Total histologic score, serum creatine kinase activity, and muscle glycogen concentration were significantly higher in horses with PSSM than in horses without. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggested that the prevalence of PSSM among overtly healthy Quarter Horses in the United States is likely to be between 6% and 12%.     

Amylopectinosis in fetal and neonatal Quarter Horses

Three Quarter Horses, a stillborn filly (horse No. 1), a female fetus aborted at approximately 6 months of gestation (horse No. 2), and a 1-month-old colt that had been weak at birth (horse No. 3), had myopathy characterized histologically by large spherical or ovoid inclusions in skeletal and cardiac myofibers. Smaller inclusions were also found in brain and spinal cord and in some cells of all other tissues examined. These inclusions were basophilic, red-purple after staining with periodic acid-Schiff (both before and after digestion with diastase), and moderately dark blue after staining with toluidine blue. The inclusions did not react when stained with Congo red. Staining with iodine ranged from pale blue to black. Their ultrastructural appearance varied from amorphous to somewhat filamentous. On the basis of staining characteristics and diastase resistance, we concluded that these inclusions contained amylopectin. A distinctly different kind of inclusion material was also present in skeletal muscle and tongue of horse Nos. 1 and 3. These inclusions were crystalline with a sharply defined ultrastructural periodicity. The crystals were eosinophilic and very dark blue when stained with toluidine blue but did not stain with iodine. Crystals sometimes occurred freely within the myofibers but more often were encased by deposits of amylopectin. This combination of histologic and ultrastructural features characterizes a previously unreported storage disease in fetal and neonatal Quarter Horses, with findings similar to those of glycogen storage disease type IV. We speculate that a severe inherited loss of glycogen brancher enzyme activity may be responsible for these findings. The relation of amylopectinosis to the death of the foals is unknown.     

Incidence of polysaccharide storage myopathy in draft horse-related breeds: a necropsy study of 37 horses and a mule.

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 present in the cardiac muscle of 1 horse. A vacuolar myopathy with aggregates of PAS-positive, amylase-sensitive glycogen was seen in 8 other horses, and these findings are also considered diagnostic for EPSSM. Antemortem serum activities of CK and AST were often higher in EPSSM horses than in horses without EPSSM. Using the presence of amylase-resistant complex polysaccharide as the criterion for diagnosis of EPSSM, the incidence in this population was 45%. Inclusion of horses with aggregates of glycogen but no amylase-resistant complex polysaccharide as representative of the range of pathologic findings in horses with EPSSM resulted in a 66% incidence in this population.     

不同比例螺旋藻多糖与银杏叶提取物对小鼠抗疲劳作用的研究

研究不同比例螺旋藻多糖与银杏叶提取物复合后对小鼠的抗疲劳作用。将螺旋藻多糖(PSP)与银杏叶提取物(GBE)按不同比例复合,以200 mg·kg~(-1)·d~(-1)剂量分别灌服小鼠,给药14 d后造小鼠疲劳模型。通过检测小鼠力竭游泳时间、血清乳酸、血清尿素氮含量、肝脏肌糖原和肝糖原含量及心脏、肝脏、脾脏和肾脏指数变化,观察复合螺旋藻多糖的抗疲劳效果。结果发现供试药物均可显著延长小鼠的力竭游泳时间,减少运动过程中乳酸和血清尿素氮的产生、加速乳酸的消除,还可增加肌糖原和肝糖原储备。另外,灌服供试药物对小鼠的体重增长、肝脏指数、肾脏指数无显著影响(P0.05),但可显著提高小鼠的心脏指数和脾脏指数(P0.01)。结果可知试验的供试药物均可显著提高小鼠的运动耐力,延缓疲劳的产生或加速疲劳的消除,具有一定的抗疲劳作用。PSP与GBE以1∶1和2∶1比例复合使用对提高小鼠的抗疲劳能力能产生较好的协同增效作用。     

Insulin sensitivity in Belgian horses with polysaccharide storage myopathy

OBJECTIVE: 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). ANIMALS: 10 Quarter Horses (QHs) and 103 Belgians in which PSSM status had been determined. PROCEDURES: 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 glucose was administered to maintain blood glucose concentration at 100 mg/dL. Activities of glycogenolytic and glycolytic enzymes were assessed in snap-frozen biopsy specimens of gluteus medius muscle obtained from 4 Belgians with PSSM and 5 Belgians without PSSM. Percentages of type 1, 2a, and 2b muscle fibers were determined via evaluation of >or= 250 muscle fibers in biopsy specimens obtained from each Belgian used in the aforementioned studies and from 10 QHs (5 with PSSM and 5 without PSSM). RESULTS: Belgians with and without PSSM were not significantly different with respect to whole-body insulin sensitivity, muscle activities of glycogenolytic and glycolytic enzymes, or proportions of muscle fiber types. However, Belgians had an increased proportion of type 2a and decreased proportion of type 2b muscle fibers, compared with proportions in QHs, regardless of PSSM status. CONCLUSIONS AND CLINICAL RELEVANCE: PSSM in Belgians may be attributable to excessive glycogen synthesis rather than decreased glycogen utilization or enhanced glucose uptake into muscle cells.     

Influence of age and breed of equid on plasma copper and zinc concentrations

Plasma ceruloplasmin activities and plasma Cu and Zn concentrations were determined in 215 clinically normal equids of various ages and breeds. Newborn foals, regardless of breed, were hypocupremic, compared with adolescent and mature horses. The mean plasma Cu concentration of newborn Standardbred-Thoroughbred (STD-TB) foals was 2.9 mumol/L, which was about one-sixth of plasma Cu concentrations of mature horses. Newborn draft-cross foals had higher (4.6 mumol/L) plasma Cu concentrations than did newborn STD-TB foals, but plasma Cu content was only one-fifth of the dams' concentrations. Draft-cross horses, regardless of age, had plasma Cu concentrations 15% to 40% higher than did STD-TB horses. Plasma Cu concentrations of Quarter Horse yearlings were similar to those in draft-cross yearlings. Plasma ceruloplasmin activities revealed a curvilinear relationship to plasma Cu concentrations. Plasma Zn concentrations of newborn and 1-week-old STD-TB foals were 30% to 80% higher than those for yearling and mature STD-TB horses. There were no differences between draft-cross neonates and their dams in plasma Zn concentration. Plasma Zn concentrations of neonatal and mature draft-cross horses were 22% higher than those obtained for all other equids. Age and breed of equid should be a consideration in interpretations of plasma Cu and Zn concentrations in equids.     

Congenital Cardiac Defects in Neonatal Foals: 18 Cases (1992–2007)

Background: Literature available regarding congenital cardiac defects in foals is limited to reports of individual cases or small case series.
Objective: To describe the clinical, echocardiographic, and necropsy findings and breed predilection of congenital cardiac defects in neonatal foals.
Animals: Eighteen foals <15 days of age with 1 or more congenital cardiac defects.
Methods: Medical records of foals diagnosed with congenital cardiac defects at the William R. Pritchard Veterinary Medical Teaching Hospital were reviewed. Data collected included history, signalment, clinical signs, laboratory data, diagnostic and necropsy results, and outcome.
Results: Arabian foals represented 39% of cases with congenital cardiac defects and were significantly ( P = .004) overrepresented (OR = 4.7 [CI: 1.8–12.4]) compared with the general hospital population. Ventricular septal defect (VSD) (14/18), tetralogy of Fallot (5/18), and tricuspid valve atresia (4/18) were the most common defects identified. A ≥3/6 heart murmur (14/14) accompanied by tachycardia (14/17), tachypnea (17/17), and cyanosis of mucous membranes (7/16) were the most common clinical signs. Concurrent congenital defects were common (9/18). Two foals, both with VSD, survived for ≥ 8 years after diagnosis and 1 was a successful performance horse.
Conclusions and Clinical Relevance: Arabian horses appear to have a predisposition for cardiac defects. The presence of a loud murmur (≥ 3/6), cyanotic membranes, and tachycardia or tachypnea in a neonatal foal should warrant thorough evaluation of the heart for congenital defects. Foals with cardiac defects should be closely evaluated for concurrent congenital defects in other body systems.     

Effect of age on liver enzyme activities in serum of healthy quarter horses

Serum alkaline phosphatase (ALP), gamma-glutamyl transferase (GGT), 5'nucleotidase (5'NT), sorbitol dehydrogenase (SDH), and aspartate transaminase activities were measured in 10 clinically healthy foals, 10 yearlings, and 10 two-year-old Quarter Horses. Enzyme activities in foals at 0.5 to 3 days, 2 to 3 weeks, and 5 to 7 weeks of age were compared with enzyme activities from yearling and 2-year-old horses. Multivariate analyses of variance revealed significantly higher enzyme values in foals (P less than 0.002). This increase was mainly a result of higher ALP and GGT activities, with lesser effects due to higher SDH and 5'NT activities. Standard deviations for ALP and GGT were also larger in foals than in adult horses. The wide variation of ALP and GGT activities may limit their usefulness in the diagnosis of hepatic disease in foals. Standard deviations for serum AST, SDH, and 5'NT activities were smaller. These enzymes may be indicators of hepatobiliary disease in foals. The high serum enzyme activities in healthy foals may reflect a physiologic difference between foals and adult horses. Relative hepatic mass (as a percentage of body weight) and enzyme activity per gram of hepatic tissue are high in young animals, indicating that the high serum enzyme activities in foals are due partly to a high rate of enzyme production and release.     

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

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

Insulin-like growth factor type-1 receptor down-regulation associated with dwarfism in Holstein calves

Perturbations in endocrine functions can impact normal growth. Endocrine traits were studied in three dwarf calves exhibiting retarded but proportionate growth and four phenotypically normal half-siblings, sired by the same bull, and four unrelated control calves. Plasma 3,5,3'-triiodothyronine and thyroxine concentrations in dwarfs and half-siblings were in the physiological range and responded normally to injected thyroid-releasing hormone. Plasma glucagon concentrations were different (dwarfs, controls>half-siblings; P<0.05). Plasma growth hormone (GH), insulin-like growth factor-1 (IGF-1) and insulin concentrations in the three groups during an 8-h period were similar, but integrated GH concentrations (areas under concentration curves) were different (dwarfs>controls, P<0.02; half-siblings>controls, P=0.08). Responses of GH to xylazine and to a GH-releasing-factor analogue were similar in dwarfs and half-siblings. Relative gene expression of IGF-1, IGF-2, GH receptor (GHR), insulin receptor, IGF-1 type-1 and -2 receptors (IGF-1R, IGF-2R), and IGF binding proteins were measured in liver and anconeus muscle. GHR mRNA levels were different in liver (dwarfs相似文献   

Persistent hypoglycemia associated with lipid storage myopathy in a paint foal

A 12‐hours‐old Paint filly was examined because of weakness and dull mentation after birth. Despite IV administered dextrose, the foal remained persistently hypoglycemic with increase in serum activity of muscle and liver enzymes. A postmortem diagnosis of lipid myopathy most similar to multiple acyl‐CoA dehydrogenase deficiency (MADD) was confirmed by findings of myofiber lipid accumulation, elevated urine organic acids, and serum free acylcarnitines with respect to control foals. This report details a case of equine neonatal lipid storage myopathy with many biochemical characteristics of MADD. Lipid storage myopathies should be included as a differential diagnosis in foals with persistent weakness and hypoglycemia.     

The Interplay of Genetics,Exercise, and Nutrition in Polysaccharide Storage Myopathy

Polysaccharide storage myopathy (PSSM), identified in 1992 in a subset of horses with exertional rhabdomyolysis, is a glycogenosis characterized by amylase-resistant polysaccharide in a small number of skeletal muscle fibers along with 1.5 to 4 times normal muscle glycogen. Extensive biochemical and physiological analyses failed to identify defects in glycogenolysis and glycolysis. In 2008, a genome-wide association analysis detected a locus on equine chromosome 10 that was strongly associated with the PSSM in Quarter Horses. Glycogen synthase 1 (GYS1), which encodes the skeletal muscle isoform of glycogen synthase (GS), was a strong candidate gene for PSSM based on its location on equine chromosome 10. Sequencing of the GYS1 gene in PSSM and control Quarter Horses identified only one single base-pair change that resulted in an amino acid substitution in the GS enzyme. Mean GS activity was higher in PSSM than control muscle homogenates in both the presence and absence of the allosteric activator glucose 6-phosphate, suggesting that the GS enzyme in horses with PSSM is constitutively active. High-grain diets increase serum insulin concentrations which further act to stimulate GS activity. An restriction fragment length polymorphism assay for the GYS1 mutation showed that 10% of the Quarter Horse breed and a minimum of 20 other breeds have the GYS1 mutation. Muscle biopsies obtained after 20 minutes of aerobic exercise revealed much higher inosine monophosphate concentrations and lower adenosine monophosphate in whole muscle and single fibers from PSSM as compared with control horse muscle. Thus, the GYS1 mutation responsible for PSSM seems to cause an energy imbalance exacerbated by high-grain diets, which results in adenine nucleotide degradation in individual muscle fibers of horses with PSSM during submaximal exercise.     

Clinical and pathological findings in a HERDA-affected foal for 1.5 years of life

A Quarter horse filly bred from two horses affected with HERDA (hereditary equine regional dermal asthenia) was observed clinically and its skin histologically for the 1.5 years of its life. Severe signs of the disease did not manifest until 1.5 years of age, and were not temporally related to saddling. Histological comparison to an age-, breed- and sex-matched control did not show any consistent diagnostic features. Monitoring of the proband substantiated previous reports of (i) the autosomal recessive nature of the disease, (ii) mares affected with HERDA being able to foal without damage to the skin or reproductive tract, (iii) HERDA foals appearing phenotypically normal throughout the first year of life, and (iv) demonstrated that histological interpretation of skin specimens from grossly normal skin may be insufficient to differentiate HERDA-affected horses from controls.     

Epidemiologic characteristics and management of polysaccharide storage myopathy in Quarter Horses

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

Glycogen storage disease type IIIa in curly-coated retrievers

BACKGROUND: Inborn errors of metabolism impose a significant genetic burden on purebred dogs and cats. The glycogen storage diseases are a category of such disorders that are typed by enzyme analysis, but deoxyribonucleic acid (DNA) based carrier tests are needed for definitive, noninvasive diagnosis and to prevent at-risk matings. HYPOTHESIS: Glycogen storage disease type IIIa (GSD IIIa) is caused by a mutation of the glycogen debranching enzyme gene (AGL) in Curly-Coated Retrievers (CCR). ANIMALS: Two CCR exhibiting episodic exercise intolerance, collapse, and lethargy, and related dogs were studied. METHODS: Structure and amount of glycogen isolated from tissue biopsy specimens was determined by enzymatic digestion, and activities of enzymes of glycogen metabolism were measured. The 33 AGL coding exons and flanking splice sites of an affected dog were amplified by polymerase chain reaction and sequenced. RESULTS: Debranching enzyme activity was undetectable in liver and skeletal muscle of affected dogs, and accumulated glycogen had absent or short outer chains of alpha1, 4-linked glucose. A single adenosine (A) deletion in AGL exon 32 of affected dog genomic DNA predicted a frame-shift and truncation of the protein product by 126 amino acid residues. The mutation was homozygous in affected dogs and heterozygous in both parents. In addition, the deletion mutation was heterozygous in 16 or not detected at all in 31 related but clinically normal CCR. CONCLUSIONS AND CLINICAL IMPORTANCE: GSD IIIa in CCR is an autosomal recessive trait caused by mutation of AGL. A DNA sequence-based carrier test was developed, and carriers were identified in the United States, New Zealand, Australia, and Finland.     

Polysaccharide storage myopathy in Morgan, Arabian, and Standardbred related horses and Welsh-cross ponies

Polysaccharide storage myopathy is an equine neuromuscular disorder characterized by accumulation of glycogen-related polysaccharide inclusions within skeletal muscle fibers. The pathologic criteria for diagnosis of this disorder are somewhat controversial; however, periodic acid-Schiff-positive, amylase-resistant inclusions are considered pathognomonic. Although these inclusions are most often found in affected horses related to the Quarter Horse, draft horse, and Warmblood breeds, this report describes these characteristic inclusions in muscle of five horses from nonrelated breeds (two Morgans, one Arabian, one Arabian x Thoroughbred, and one Standardbred) and two Welsh cross ponies. Affected horses had histories of recurrent exertional rhabdomyolysis, and one developed progressive weakness leading to increased recumbency. The affected ponies were part of an unrelated research project and had no apparent clinical signs.