(Nelson) Muscle Diseases

Question 1

Spinal Muscular Atrophy

Name:

1) Affected Structure
2) Affected Gene
3) Who’s affected
4) Most common form

Answer 1

• Distinctive group of autosomal recessive motor neuron diseases that present in childhood or adolescence.
• All forms of SMA are associated with mutations affecting survival motor neuron 1 (SMN1), a gene on chromosome 5 that is required for motor neuron survival.
• The most common form of SMA is known as Werdnig-Hoffmann disease.

Question 2

Name the two most common forms of childhood Muscular Dystrophy.

What chromosome & protein is affected in these disorders?

What is the difference in protein expression between the two?

Answer 2

Duchenne muscular dystrophy (DMD) and Becker muscular dystrophy (BMD).

caused by mutations of an X-linked gene (Xp21 region) that encodes for a protein named dystrophin

Patients with DMD have little or no dystrophin; patients with BMD have decreased amounts of dystrophin or a defective, abnormal form of dystrophin.

Question 3

Clinical Presentation of DMD

Answer 3

Patients with DMD usually develop symptoms by age 5, with weakness in the pelvic girdle, followed by the shoulder girdle. Patients may have a waddling “duck-like” gait and place hands on knees to assist in standing (Gower’s maneuver); may also see “pseudohypertrophy” of the calf muscles; patients are often wheel chair dependant by 10-12 years; complications include respiratory insufficiency with infections and cardiomyopthy, with median survival approximately 35 years.

Question 4

Clinical Presentation of BMD

Answer 4

Patients with BMD have a later onset with milder symptoms, and can survive well into the 40’s and beyond.

Question 5

Most common form of Adult MD

Answer 5

MYOTONIC DYSTROPHY

Question 6

What is Malignant hyperpyrexia/hyperthermia?

Answer 6

an ion-channel myopathy triggered by certain inhalational anesthetics.

Rare clinical syndrome characterized by a marked hypermetabolic state

Question 7

Three subgroups of inflammatory myopathies:

Answer 7

Infectious (Gangrene, group A strep infection)

Associated with systemic inflammatory disease (Lupus)

Noninfectious inflammatory disease (Dermatomyositosis)

Question 8

Dermatomyositis

vs.

Polymyositis

vs.

Inclusion Body Myositis

Answer 8

Dermatomyositis

Inflammatory disorder of skin and skeletal muscle.

Classic rash is violaceous discoloration of **upper eyelids **

20-25% of patients with dermatomyositis have an underlying malignancy!

Pathogenesis is thought to be related to immunologic injury to small blood vessels and capillaries in the skeletal muscle.

Polymyositis

Muscle and systemic involvement is similar to that seen in dermatomyositis, except for the **lack of skin involvement. **

No vascular injury is seen.

Inclusion Body Myositis

Begins with the involvement of distal muscles, in contrast to dermatomyositis and polymyositis.

Question 9

Classic Labs for diagnosis of Myopathies

Answer 9

ELEVATED Myoglobin and CREATININE KINASE!

Elevations in these occur when skeletal muscle has been damaged.

Creatine kinase is cytosolic enzyme which converts creatine to phoshocreatine; in the process ATP is converted to ADP.

Creatine kinase exists as three isoenzymes: CK-BB, CK-MB, and CK-MM (B = brain, M = muscle) .

Skeletal muscle primarily expresses CK-MM (98%) with very low levels of CK-MB; however, as skeletal muscle is damaged and regeneration occurs, skeletal muscle can exhibit increased CK-MB expression. Cardiac muscle expresses CK-MM (70%) and CK-MB (20-25%). CK-BB is expressed at low levels in many tissues.

CK-MB isoenzyme is used primarily for the diagnosis of acute myocardial infarct, along with cardiac troponin I; while cardiac troponin I is specific for cardiac muscle, CK-MB is not. As such, cardiac troponin I is the preferred enzyme to measure for detection of myocardial injury.

Total CK is helpful in the assessment of skeletal muscle injury, in the absence of cardiac disease or other conditions that may cause increased CK

Question 10

What is MYASTHENIA GRAVIS?

*Name a condition that presents similarly

Answer 10

An autoimmune disease of the neuromuscular junction, caused by immune mediated loss of acetylcholine receptor (AChR).

is often associated with thymic abnormalities

*LAMBERT-EATON MYASTHENIA! autoantibodies directed against calcium channels; this condition is often seen as a paraneoplastic syndrome, with malignancy present in 60% of cases