Diseases of Muscle 2 Flashcards
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
Duchenne vs Becker
Dystrophine found in Western blot:
DMD<5%
Intermediate 5-20%
BMD>20%
Fascioscapulohumeral dystrophy: diagnosis and management
The management of FSHD is primarily supportive, as no disease-modifying therapy is available.
The main focus of management involves physical therapy and rehabilitation, exercise, pain control, and orthopedic interventions.
Other issues requiring surveillance include potential pulmonary, ophthalmologic, and auditory problems related to FSHD.
