EXAM 1 Skeletal Muscles II

Question 1

2 Types of Inherited Diseases of Skeletal Muscle

Answer 1

Congenital Myopathy

Muscular Dystrophy

Question 2

Congenital Myopathy Pathology

Answer 2

• Defect in contractile apparatus/excitation-contraction coupling at NMJ
• At birth or soon after
• Mostly non-progressive/static
• Normal CK (creatinine kinase)
• problem in contractile unit - weakness doesn’t progress*
• no muscle damage”

Question 3

Muscular Dystrophy Pathology

Answer 3

• Membrane Damage Necrosis
• Infancy to late adulthood
• Progressive weakness
• Elevated CK
• muscle damage not repairable*

Question 4

Muscular Dystrophy

Answer 4

Characterized by progressive muscle damage that typically comes to attention after infancy

Question 5

Muscular Dystrophy Types

Answer 5

1) Defects in extracellular matrix
- *Ullrich congenital MD: collagen 6 deficiency
- *Merosin deficiency: Merosin basement membrane protein
* Cogenital - “floppy infant”, hyperextensive joints
2) Receptor defects for extracellular matrix
- Dystrophinopathies (Duchenne & Becker muscular dystrophies)
- Limb-Girdle dystrophies
- Myotonic dystrophy
- Facioscapulohumeral and scapuloperoneal dystrophy
- Oculopharyngeal muscular dystrophy
- Emery-Dreifuss muscular dystrophy

Question 6

Duchene and Becker Pathology

Answer 6

• X linked (most common)
• Loss of function mutations in Dystrophin gene
• Severe Progression
• Role of Calcium in pathogenesis (too much Ca influx leads to myofiber degeneration)

Question 7

Duchene and Becker Clinical Features

Answer 7

• Pseudohypertrophy: Muscle tissue is replaced by collagen and fat cells (“fatty replacement” or “fatty infiltration”).
• Uses hands to push on legs to stand up (Gower’s sign)
• Mean age of wheelchair dependence is 9.5 years
• Death due to heart or lung causes

Question 8

Myotonic Dystrophy

Answer 8

• Autosomal dominant - skeletal muscle weakness, cataracts, endocrinopathy, and cardiomyopathy.
• It affects about 1 in 10,000 individuals.
• Myotonia, a sustained involuntary contraction of muscles, is a key feature of the disease.

Question 9

Myotonic Dystrophy Pathology

Answer 9

Expansions of CTG triplet repeats in myotonic dystrophy protein kinase (DMPK) gene. Disrupts protein which regulates Cl channel in skeletal muscle.

Question 10

Limb-Girdle Muscular Dystrophy

Answer 10

• Characterized by muscle weakness that preferentially involves proximal muscle groups ie. perlvic and shoulder girdle.
• Any age onset

Question 11

Spinal Muscular Atrophy

Answer 11

Neuropathic disorder in which loss of motor neurons leads to muscle weakness and atrophy.

Question 12

Spinal Muscular Atrophy Pathology

Answer 12

• Autosomal recessive - incidence of 1 in 6,000 births.

- Caused by loss-of-function mutations in the SMN1 (survival of motor neuron-1) gene.

Question 13

Spinal Muscular Atrophy Clinical Features

Answer 13

• Generalized hypotonia - “floppy infant”.
• Characteristic morphologic changes consisting of large zones of severely atrophic myofibers mixed with scattered normal sized or hypertrophied myofibers, found individually or in small groups.

Question 14

Diseases of lipid or glycogen metabolism

Answer 14

• lipid accumulation inside the cell
• Exercise or fasting + progressive muscle damage = Severe muscle cramping and pain, Extensive muscle necrosis (rhabdomyolysis)

Question 15

Carnitine palmitoyltransferase II deficiency

Answer 15

• most common disorder of lipid metabolism to cause episodic muscle damage with exercise or fasting
• Defect in the transport of long chain fatty acids to mitochondria for β-oxidation

Question 16

Myophosphorylase deficiency (McArdle disease)

Answer 16

• is one of the more common glycogen storage diseases affecting skeletal muscle; it also results in episodic muscle damage with exercise.
• Defect in glycogen to glucose breakdown

Question 17

Acid maltase deficiency

Answer 17

Defect in lysosomal conversion of glucose to glycogen causing glycogen to accumulate within lysosomes. (enzyme replacement therapy available)

Question 18

2 Types of Acid maltase deficiency

Answer 18

Mild deficiency: Adult onset myopathy with lungs involved
Severe deficiency: Pompe Disease (absence or deficiency of the lysosomal enzyme alpha-glucosidase (GAA). This enzyme is required to breakdown (metabolize) the complex carbohydrate glycogen and convert it into the simple sugar glucose.)

Question 19

Mitochondrial Myopathies

Answer 19

• Defect in ATP synthesis - skeletal muscles, cardiac muscles, neurons
• Manifestations: weakness, elevations in serum creatine kinase levels, or rhabdomyolysis.

Question 20

Ion Channel Myopathies (Channelopathies)

Answer 20

• Group of inherited diseases caused by mutations affecting the function of ion channel proteins
• Problem with the ion channels that don’t allow for muscle movement: sodium, potassium, chloride, and calcium channels

Question 21

Ion Channel Myopathies Clinical Manifestations

Answer 21

epilepsy, migraine, movement disorders with cerebellar dysfunction, peripheral nerve disease, and muscle disease.

Question 22

Ion Channel Myopathies Types

Answer 22

Periodic Paralysis

• Hyperkalemic (work against hyper-polarization (increases the positivity w/in a cell, which is depolarization))
• Hypokalemic
• Normokalemic

Question 23

Ion Channel Myopathies - type RYR1

Answer 23

Mutations in the RYR1 gene disrupts the function of the ryanodine receptor which regulates Ca release in the sarcoplasmic reticulum.

Question 24

Ion Channel Myopathies - RYR1 mutations are linked to congenital myopathies and _________.

Answer 24

Malignant hyperthermia

Question 25

Ion Channel Myopathies - type KCNJ2

Answer 25

Mutations affecting this K channel cause Andersen-Twail Syndrome (autosomal disorder) associated with periodic paralysis, heart arrhythmias, and skeletal abnormalities.

Question 26

Ion Channel Myopathies - type SCN4A

Answer 26

Mutations affecting this Na channel cause several autosomal disorders that present with myotonia to periodic paralysis.