Week 4 - Muscle Diseases

Question 0

What happens in all muscular dystrophies?

Answer 0

Muscle atrophy & wasting, with muscle replaced by fibrofatty tissue.

Question 1

What genetic defect is involved in spinal muscular atrophy?

Answer 1

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)

Question 2

What gene mutation causes DMD and BMD? What kind of disorders are they?

Answer 2

X-linked disorders

-Caused by mutations in X-linked gene (Xp21 region) that encodes for DYSTROPHIN.

Question 3

What does dystrophin do?

Answer 3

It transfers contractile force to the connective tissue.

-connects cytoskeletal proteins and transmembrane proteins

Question 4

What is the difference between DMD and BMD in terms of dystrophin?

Answer 4

DMD has little or no dystrophin.

BMD have decreased amounts of dystrophin or a defective, abnormal form of dystrophin.

Question 5

Describe the pathogenesis of DMD.

Answer 5

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

Question 6

Describe the pathogenesis of BMD.

Answer 6

• Later onset & milder symptoms
• Survive well into & beyond 40s
• May also be wheelchair bound and have cardiac problems or respiratory problems

Question 7

What is myotonic dystrophy and what genetic defect causes it?

Answer 7

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

Question 8

What is malignant hyperpyrexia (malignant hyperthermia)? What genetic defect causes it?

Answer 8

• 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)

Question 9

What are the three subgroups of inflammatory myopathies?

Answer 9

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:
   (1) Dermatomyositis
   (2) Polymyositis
   (3) Inclusion body myositis

Question 10

What is dermatomyositis?

Answer 10

Immunologic disease with immunologic injury & DAMAGE TO SMALL BLOOD VESSELS and capillaries in the skeletal muscle
-Autoantibodies involved

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

Question 11

What is Polymyositis?

Answer 11

It has muscle and systemic involvement like dermatomyositis, but LACKS SKIN INVOLVEMENT

• seen mainly in adults
• Has some autoantibodies - no vascular injury seen
• Muscle weakness

Question 12

What is inclusion body myositis?

Answer 12

• 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

Question 13

What is myasthenia gravis & what causes it?

Answer 13

-Autoimmune disease
-Produce ACh receptor autoantibodies <-immune mediated loss of function of AChR
Patients have: -muscle weakness -THYMIC (thymus) abnormalities, thymic hyperplasia thyoma

Question 14

What is Lambert-Eaton myasthenia syndrome? What causes it? What are its symptoms?

Answer 14

-Immune disorder
-Autoantibodies for presynaptic Ca2+ channels
-This blocks ACh release
Symptoms:
-Extreme weakness
-Rapid repetitive stimulation of the affected muscle increases the muscle response
-Non-thymic malignancies

Question 15

What is the general cause of elevated creatine kinase?

Answer 15

Its released into the interstitial space and blood when cells are damaged

Question 16

What are specific causes of elevated creatine kinase?

Answer 16

Acute myocardial infarct
Myocardial injury
Inflammatory myopathies
Muscular dystrophies
Rhabdomyolysis
Skeletal Muscle Trauma
Head injury
 [Cardiac troponin I - specific for cardiac muscle]