Flashcards in Week 4 - Muscle Diseases Deck (17)
What genetic defect is involved in spinal muscular atrophy?
Group of mainly autosomal recessive motor neuron diseases
Mutations affecting survival motor neuron 1 (SMN1), a gene on chromosome 5 that is required for motor neuron survival (patients exp. loss of motor neurons which leads to muscle atrophy & weakness)
What happens in all muscular dystrophies?
Muscle atrophy & wasting, with muscle replaced by fibrofatty tissue.
What gene mutation causes DMD and BMD? What kind of disorders are they?
-Caused by mutations in X-linked gene (Xp21 region) that encodes for DYSTROPHIN.
What does dystrophin do?
It transfers contractile force to the connective tissue.
-connects cytoskeletal proteins and transmembrane proteins
What is the difference between DMD and BMD in terms of dystrophin?
DMD has little or no dystrophin.
BMD have decreased amounts of dystrophin or a defective, abnormal form of dystrophin.
Describe the pathogenesis of DMD.
1:3500 males, 2/3 cases familial
-Symptoms by age 5
-Weakness in pelvic girdle, followed by shoulder girdle
-Duck-like-gait- Gower's maneuver
-Pseudohypertrophy of calf muscles
-Median survival 35 yrs
-Creatine kinase increased early in disease, even before symptoms
Describe the pathogenesis of BMD.
-Later onset & milder symptoms
-Survive well into & beyond 40s
-May also be wheelchair bound and have cardiac problems or respiratory problems
What is myotonic dystrophy and what genetic defect causes it?
It's the most common adult muscular dystrophy and involves involuntary contraction of a group of muscles.
-Autosomal dominant disorder
-Inc. CTG trinucleotide repeat seq. on chromonsome 19 (trinucleotide repeat disorder) -> affects mRNA for dystrophia myotonia protein kinase (DMPK) -> defects affecting transcription of chloride channel, CLC1 -> myotonia
What is malignant hyperpyrexia (malignant hyperthermia)? What genetic defect causes it?
-Marked hypermetabolic state (tachycardia, tachypnea, muscle spasms, later hyperpyrexia) triggered by certain inhaled anesthetics
-Associated with several mutations that encode proteins that control cytosolic calcium
-When exposed to anesthetic, abnormal Ca2+ channels allow uncontrolled calcium to be released --> leads to increased muscle metabolism, excessive heat production, tetany (seizure like contractions)
What are the three subgroups of inflammatory myopathies?
1. Infectious (group A strep, gas gangrene, necrotizing fasciitis,etc.)
2. Associated with systemic inflam. disease (lupus (SLE), rheumatoid arthritis (RA), etc.)
3. Noninfectious inflammatory disease:
(3)Inclusion body myositis
What is dermatomyositis?
Immunologic disease with immunologic injury & DAMAGE TO SMALL BLOOD VESSELS and capillaries in the skeletal muscle
Clinical: MUSCLE WEAKNESS & SKIN RASH, discoloration of upper eyelids associated with periorbital edema, red patches over the knuckles, elbows, and knees
-Muscle weakness usually effects proximal muscles first & is symmetric
What is Polymyositis?
It has muscle and systemic involvement like dermatomyositis, but LACKS SKIN INVOLVEMENT
-seen mainly in adults
-Has some autoantibodies - no vascular injury seen
What is inclusion body myositis?
-Most common inflammatory myopathy in patients older than 65
-Begins with involvement of distal muscles
-Muscle involvement may be assymetric
-Dont know if it is an inflammatory condition or a degenerative process with secondary inflammation
What is myasthenia gravis & what causes it?
-Produce ACh receptor autoantibodies <-immune mediated loss of function of AChR
Patients have: -muscle weakness -THYMIC (thymus) abnormalities, thymic hyperplasia thyoma
What is Lambert-Eaton myasthenia syndrome? What causes it? What are its symptoms?
-Autoantibodies for presynaptic Ca2+ channels
-This blocks ACh release
-Rapid repetitive stimulation of the affected muscle increases the muscle response
What is the general cause of elevated creatine kinase?
Its released into the interstitial space and blood when cells are damaged