Heritable muscle disorders Flashcards
Describe the main features of PSSM
- twofold higher glycogen concentrations in skeletal muscle
- abnormal granular amylase-resistant inclusions in skeletal muscle
- autosomal dominant point mutation in the glycogen synthase 1 gene (GYS1) that appears to cause upregulated synthesis of glycogen
What is the difference between type 1 and type 2 PSSM?
Type 1 PSSM: horses with the GYS1 mutation
Type 2 PSSM: horses diagnosed with abnormal glycogen storage in muscle biopsy that lack the GYS1 mutation
What are the clinical signs of PSSM in Quarter horses?
- firm, painful muscles
- stiffness
- fasciculations
- sweating
- weakness
- reluctance to move
- hindquarters frequently most affected —> back muscles, abdomen and forelimb muscles may also be involved
- may stop and posture as if to urinate during exercise
- signs of pain can be severe and 30% of horses have muscle pain for > 2hours and approx. 10% become recumbent
- muscle pain often occurs with <20mins exercise at walk and trot esp. if horse has been rested for several days and is on high-grain diet
Less common signs: - gait abnormalities
- mild colic
- muscle wasting
What are the clinical signs of PSSM in Draft horses?
- Belgian and Percherons have high prevalence of Type 1 PSSM
- many do not have clinical signs
- severe rhabdomyolysis and myoglobinuria in horses fed high-grain diet, exercised irregularly with little turnout or undergoing GA
- progressive weakness and muscle loss resulting in difficulty rising in horses with normal CK
- gait abnormalities eg. excessive limb flexion, fasciculations, trembling
What are the clinical signs of PSSM in Warmbloods?
- painful, firm back and hindquarter muscles
- reluctance to collect and engage hindquarters
- poor rounding over fences
- gait abnormalities
- muscle atrophy
- overt signs of rhabdomyolysis in <15% of Warmbloods with PSSM
How is PSSM diagnosed?
- genetic testing for Type 1 PSSM - whole blood or hair roots
- if definitive dx required all at once, submission of genetic test and muscle biopsy most expedient
- muscle biopsy (type 1): amylase-resistant granular polysaccharide in amylase-periodic acid Schiff (PAS) stains
- Type 2: muscle biopsy —-> increased or abnormal PAS-positive material that is usually amylase-sensitive
- high chance of false + —-> need full evaluation to rule out other underlying causes of performance problems
What other supporting evidence can be used for a diagnosis of PSSM?
Quarter Horses: clinical signs of ER, persistent elevations in serum CK and AST, minimum of three-fold elevation in CK 4 hours after exercise test (max 15mins lunging at walk and trot)
Draft and Warmbloods: exercise intolerance, muscle atrophy, weakness, some gait abnormalities without necessarily finding increased muscle enzymes
Discuss the important aspects of exercise in the management of horses with PSSM.
Exercise
1) provide adequate time for adaptation to new diet prior to commencing exercise
2) duration of exercise, not just intensity, should be restricted
3) ensure exercise is gradually introduced and consistently performed
4) minimise days without some form of exercise
- if horses have recently had episode of rhabdomyolysis, 2 weeks turnout and diet change often beneficial before restarting exercise
- exercise should be very relaxed
- successive daily addition of 2-minute intervals of walking and trotting beginning with 4mins and working up to 30mins after 3 weeks
- work under saddle after 3 weeks groundwork in gradually accelerating program that adds 2-minute intervals of collection or canter
- keeping horses fit is good prevention against further episodes
- gradual approach to reintroducing exercise aims to enhance oxidative capacity of skeletal muscle without causing further cellular damage —> objective of enhancing oxidative metabolism is to facilitate the metabolism of fat and blood glucose as energy substrates
How long should horses be rested after an episode of PSSM?
Rest
- horses should be confined to a stall for 48hrs or less after an episode of rhabdomyolysis and access to turnout should be provided with little grain supplementation
Discuss the important aspects of diet in the management of horses with PSSM.
- if overweight, reduce caloric intake by using grazing muzzle, restricting hay to 1.5% BW and providing ration balancer
- once horse has achieved desired BW, dietary modification should combine reducing glucose load and providing fat as alternate energy source
- low-starch, high-fat diets —-> less glucose uptake into muscle cells and provision of more plasma free fatty acids for use in muscle fibres during aerobic exercise
- provision of < 10% DE as starch and at least 13% as fat - reduces CK activity to normal values after exercise
- significant variation in individual tolerance to dietary starch - horses with more severe clinical signs appear to require greatest restriction in starch intake
- exercise program must also be instituted for horses to show clinical improvement
- commercial diets available: 10-15% fat and <20% starch or NSC
Describe the specific genetic mutation involved in HYPP
- autosomal dominant trait
- single base-pair substitution in the SCN4A gene —> causes a phenylalanine/leucine substitution in a key part of the voltage-dependent skeletal muscle sodium channel alpha-subunit
Describe the clinical signs of HYPP
- clinically normal b/w epsidoes
- severity of clinical signs highly variable
- expression of HYPP influenced by dietary potassium conc, epsiodes of feed withdrawal or inappetence, heavy sedation, anaesthesia, trailer rides and stress
- often no inciting cause
- exercise doesn’t usually induce clinical signs
- most clinical episodes characterised by: increased facial muscle tone, occasional prolapse of 3rd eyelid, sweating, muscle fasciculations in flanks, neck, shoulders
- muscle fasciculations may spread to additional muscle groups and can be exacerbated by sensory stimulation
- some may develop severe muscle cramping
- persistent depolarisation of the muscle can progress to cause weakness characterised by staggering, dogsitting and recumbency
- episodes often last 15-60mins - horses remain anxious but alert
- resp stridor, distress and dysphagia may occur esp in homozygous horses as result of pharyngeal collapse and oedema, laryngopalatal dislocation and laryngeal paralysis
How is HYPP diagnosed?
- blood samples during epsiodes: hyperkalaemia (6-9mEq/L), haemoconcentration and mild hyponatraemia
- these changes occur because subpopulation of skeletal muscle sodium channels fail to inactivate, resulting in excessive inward flux of sodium and outward flux of potassium from muscle cells
- serum K+ conc return to normal soon after episode
- for dx at other time: electromyography —-> persistent abnormal findings include fibrillation potentials, complex repetitive discharges with occasional myotonic potentials, trains of doublets
- definitive test: demonstration of base-pair sequence substitution in segment of gene encoding for the alpha-subunit of the sodium channel —> requires submission of mane or tail hair to licensed lab
- DDx for hyperkalaemia: delay before sample centrifugation, haemolysis, acidosis, renal failure, severe rhabdomyolysis, high-intensity exercise
What is the recommended treatment for HYPP?
- some may spontaneously recover
- mild exercise or administration or corn syrup may abort mild episode
- severe cases: Ca gluconate IV (0.2-0.4mL/kg) of a 23% solution diluted in 1L 5% dextrose or saline OR dextrose (6mL/kg) of a 5% solution alone or combined with Na bicarbonate (1-2mEq/kg) OR epinephrine (3mL of 1:1000/500 kg) IM
- administration of calcium lowers the depolarisation threshold and should make muscle cell membranes less likely to depolarise
- if signs of resp distress, may need tracheostomy
What are the important aspects of control of HYPP?
- horses should be fed balanced diet containing 0.6%-1.1% total potassium. Each meal should contain < 33g K+
- avoid high K+ feeds eg. alfalfa hay, orchard grass hay, brome hay, soybean meal, sugar molasses and beet molasses
- later cuts of Timothy or Bermuda grass hay, grains such as oats, corn, wheat and barley and beet pulp should be fed in small meals several times a day
- regular exercise or frequent access to large paddock
- acetazolamide (2-3mg/kg PO q8-12h) or hydrochlorothiazide (0.5-1mg/kg PO q12h) for horses in which episodes not controlled y adjusting diet. These diuretics increase renal K+ excretion and acetazolamide also stimulates insulin secretion which drives blood glucose and potassium into cells
