Diseases of Muscle 2 Flashcards
(34 cards)
Primary metabolic myopathies chief symptoms
exercise intolerance
muscle weakness or fatigability
myalgias
cramps
myoglobinuria
Which are the primary metabolic myopathies (common)
1) Acid maltase deficiency (Pompe)
2) Myophosphorylase deficiency (McArdle)
3) Phosphofructokinase deficiency
4) Carnitine palmitoyltransferase deficiency
5) Myoadenylate deaminase deficiency (Adenosine monophosphate deaminase 1) (probably the most common)
Forearm ischemic exercise test: where is it useful, how is it performed, complications
useful for screening glycogen storage disorders such as
- myophosphorylase deficiency
- myoadenylate deaminase deficiency
- phosphofructokinase deficiency
Prior to the test, baseline venous lactate and ammonia levels should be obtained. To perform the test, a blood pressure cuff is placed over the patient’s upper arm and inflated to a pressure roughly 20 mm Hg greater than the systolic pressure that renders the forearm ischemic.
The patient then immediately begins repetitive, rapid grip exercises (eg, squeezing a ball or hand ergometer) for as long as possible. The test is aborted if the patient develops a cramp or contracture during cuff inflation or exercise. When the patient fatigues, the cuff is released and blood is drawn at 1, 3, 5, 10, and 15 minutes postexercise for evaluation
of elevated lactate and ammonia levels.
The test should be performed with caution, because of the risk of compartment syndrome with ulnar nerve damage or severe rhabdomyolysis that may lead to renal failure.
Ischemic forearm exercise test
Acid maltase (a-glucosidase) deficiency (Pompe): inheritance, clinical findings, laboratory findings, FIET results, EMG findings, muscle biopsy findings, treatment
Diagnosis:
Η διάγνωση της νόσου είναι πρωτίστως βιοχημική.
Το gold standard είναι η μέτρηση της δραστηριότητας του ενζύμου σε καλλιέργεια ινοβλαστών.
Demonstration of reduced Acid alpha-glucosidase (GAA) activity in a dried blood spot or leukocytes, followed by sequencing of the GAA gene, confirms the disease.
EMG: Χαρακτηριστικό οι μυοτονικές ή ψευδομυοτονικές εκφοτρτίσεις στους παρασπονδυλικούς μύες!
Treatment:
Enzyme replacement therapy + in some patients miglustat –>
Φαρμακολογική σαπερόνη: μόριο που σταθεροποιεί το ένζυμο
++ The forced vital capacity (FVC) on pulmonary function testing typically is reduced substantially in adults.
Myophosphorylase deficiency: inheritance, clinical findings, laboratory findings, FIET results, EMG findings, muscle biopsy findings, treatment
Diagnosis: genetic testing
Muscle biopsy only when DNA sequencing is inconclusive
Treatment:
Diet – A carbohydrate-rich diet may be of benefit for patients with myophosphorylase deficiency
Exercise – Patients with myophosphorylase deficiency should perform regular mild-to-moderate physical activity under medical supervision
++ “second wind” phenomenon: an improvement in myalgias, muscle stiffness, initial fatigue, and tachycardia after approximately 10 minutes of exercise
Phosphofructokinase deficiency: inheritance, clinical findings, laboratory findings, FIET results, EMG findings, muscle biopsy findings, treatment
Carnitine palmitoyltransferase deficiency: inheritance, clinical findings, laboratory findings, FIET results, EMG findings, muscle biopsy findings, treatment
Diagnosis: Confirmatory testing is through the demonstration of mutations in the CPT1A gene or enzyme activity in skin fibroblasts.
Treatment:
fasting avoidance, a low-fat diet with medium chain triglyceride supplementation or triheptanoin, and supportive care during illness
Carnitine supplementation has not been therapeutic.
Myoadenylate deaminase deficiency (Adenosine monophosphate deaminase 1): inheritance, clinical findings, laboratory findings, FIET results, EMG findings, muscle biopsy findings, treatment
Molecular genetic testing may reveal homozygosity or compound heterozygosity for AMPD1 pathogenic variants
The most common metabolic cause of recurrent myoglobinuria in both adults and children
carnitine palmitoyltransferase 2 deficiency
Algorithm for the diagnosis of metabolic myopathies
https://www.uptodate.com/contents/image?imageKey=PEDS%2F71018&topicKey=PEDS%2F6193&search=primary%20metabolic%20myopathies&rank=1~150&source=see_link
When should the diagnosis of a possible metabolic myopathy be considered
in patients with dynamic symptoms (eg, exercise intolerance, acute reversible weakness, myoglobinuria) or static symptoms (eg, fixed weakness, cardiomyopathy, neuropathy).
Causes of myoglobinuria
Characteristics of urine, complications and management
Urine is characteristically brownish to dark red and tests positive for heme by the dipstick test despite the absence of red blood cells on microscopic examination
Acute myoglobinuric renal failure and life-threatening electrolyte disturbances are the most dreaded complications.
In severe cases, treatment may require peritoneal dialysis or hemodialysis; patients with milder disease can be treated with aggressive hydration, alkalinization of urine with sodium bicarbonate, and correction of electrolyte disturbances. The underlying disorder should be specifically treated.
Which are the channelopathies
1) hypokelamic periodic paralysis
2) hyperkalemic periodic paralysis
3) Paramyotonia congenita
4) Myotonia congenita (Thomsen)
5) Generalized myotonia (Becker)
6) Malignant hyperthermia
Channelopathies: clinical findings and treatment
Hypokalemic periodic paralysis: clinical findings, precipitating factors, treatment and prophylaxis
Episodic attacks of weakness lasting hours to days
Loss of deep tendon reflexes during attacks
Precipitating factors: carbohydrate load, postexercise period, pregnancy, emotional stress, cold
Treatment: Potassium chloride PO
Prophylaxis: Acetazolamide or Spironolactone
Malignant hyperthermia: symptoms, precipitating factors, etiology and associated diseases, treatment
Malignant hyperthermia is characterized by acute severe fever, tachypnea, tachycardia, and rigidity, and high mortality rate if left untreated.
It is typically precipitated by volatile anesthetics, especially halothane, or muscle relaxants such as succinylcholine.
Patients may become severely acidotic and develop rhabdomyolysis.
Pathology shows diffuse segmental muscle necrosis.
It appears to be a metabolic myopathy in which there is abnormal release of calcium from the sarcoplasmic
reticulum and ineffectual uptake afterward.
Genetic defects in the ryanodine receptor, involved in calcium
flux in the sarcoplasmic reticulum, are responsible for about 10% of cases
It is inherited in an autosomal dominant fashion.
Certain other myopathies, including Duchenne muscular dystrophy and central core myopathy, are associated with this condition as well.
Treatment consists of discontinuation of anesthesia, administration of dantrolene, which prevents release of calcium from the sarcoplasmic reticulum, and supportive measures.
Difference between paramyotonia congenita and myotonia congenita (Thomsen)
Στη συγγενή παραμυοτονία
1) η αδυναμία εμφανίζεται μετά από έκθεση στο κρύο.
2) Συχνά υπάρχει περιοδική υπερκαλιαιμική παράλυση με την πτώση της θερμοκρασίας.
3) Υπάρχει το φαινόμενο της “παράδοξης μυοτονίας”: η μυοτονία επιδεινώνεται με την άσκηση σε αντίθεση με την οικογενή μυοτονία όπου η άσκηση βελτιώνει τα συμπτώματα
Duchenne muscular dystrophy: etiology and clinical findings
Most cases are X-linked recessive, although 30% involve spontaneous new mutations
Onset: 2-5 years
Pseudohypertrophy
Gowers maneuver
Between the ages of 7 and 12 years, most patients lose their ability to walk and become wheelchair dependent.
Diminished IQ
Cardiac involvement
Rapid decline
Fatty infiltration of the heart and respiratory infections often lead to death
Death by age 20-30 years
Duchenne muscular dystrophy: diagnosis
A dystrophinopathy is usually suspected in a boy with muscle weakness, myopathic signs, and (possibly) a family history of the illness.
Molecular genetic testing is indicated for patients with an elevated serum CK level and clinical findings suggestive of a dystrophinopathy.
The diagnosis is established if a disease-causing mutation of the DMD gene is identified.
Although seldom necessary, a muscle biopsy with dystrophin analysis can confirm the diagnosis if the genetic studies are negative or equivocal.
Duchenne muscular dystrophy: management
-
Disease-modifying therapy –
Glucocorticoids are the mainstay of pharmacologic treatment for Duchenne muscular dystrophy
Prednizone 0.75mg/kg/day for children with DMD age four years or older whose motor skills have plateaued or have started to decline
Genetic therapies (eteplirsen, golodirsen, viltolarsen, and ataluren) are available in some countries; these therapies increase dystrophin expression, but clinical benefit has not been established.
++ Little is known of the effect of glucocorticoids in patients with Becker muscular dystrophy
- dietary calcium and vitamin D supplementation
- Cardiac management – For patients with DMD, a baseline assessment of cardiac function, including electrocardiogram and noninvasive cardiac imaging, is recommended at the time of diagnosis and at least annually thereafter.
For boys with DMD, we recommend initiation of an angiotensin converting enzyme (ACE) inhibitor or an angiotensin receptor blocker (ARB) beginning by age 10 years -
Respiratory management –
Serial monitoring of vital capacity should begin when the individual is five to six years of age and followed yearly during the ambulatory stage.
When patients become nonambulatory, more extensive monitoring should occur at least every six months.
The core respiratory therapies for DMD are lung volume recruitment, assisted coughing, nocturnally assisted ventilation, and subsequent daytime ventilation. In most cases, the need for these interventions arises after loss of ambulation.
Duchenne muscular dystrophy and surgery risk
Patients with DMD have a high risk of complications when they undergo surgery or procedures requiring anesthesia or sedation, and should have preoperative evaluations by pulmonary, anesthesia, and cardiac specialists prior to any surgery.
Total intravenous anesthesia is indicated for patients with DMD.
Succinylcholine (a depolarizing neuromuscular blocking agent) and certain inhalational anesthetics are absolutely contraindicated because they carry an unacceptable risk of life-threatening hyperkalemia and rhabdomyolysis.
Becker muscular dystrophy: etiology and clinical findings
mutations of the dystrophin gene
X-linked recessive
Compared with DMD, the age of onset of symptoms of those with BMD is usually later and the degree of clinical involvement milder.
Patients with BMD typically remain ambulatory beyond the age of 16 years and often well into adult life, and usually survive beyond the age of 30 years.
Duchenne vs Becker
Dystrophine found in Western blot:
DMD<5%
Intermediate 5-20%
BMD>20%
