Degenerative Diseases part 2

Question 1

Where is the dysfunction with Spinocerebellar Degenerations?

Answer 1

Cerebellum
Spinal cord
Peripheral nerves

Question 2

Spinocerebellar Ataxias are a group of disorders that involve spinocerebellar degenerations. How are they inherited and what gene mutation is involved?

Answer 2

Autosomal Dominant inheritance

– SCA mutations

Question 3

What are 3 Spinocerebellar Degenerations?

Answer 3

1. Friedreich Ataxia
2. Ataxia-Telangiectasia
3. Amyotrophic Lateral Sclerosis

Question 4

What are 3 Spinocerebellar Degenerations?

Answer 4

1. Friedreich Ataxia
2. Ataxia-Telangiectasia
3. Amyotrophic Lateral Sclerosis

Question 5

What trinucleotide repeat is present with Friedreich Ataxia?

Answer 5

GAA

Question 6

With Friedreich Ataxia, what protein is decreased?

Answer 6

Frataxin

Question 7

What presents in the 1st decade of life with Friedreich Ataxia?

Answer 7

Gait ataxia

Question 8

As Friedreich Ataxia progresses, what symptoms are unique?

Answer 8

Cardiomyopathy

– increased arrhythmias and congestive heart failure

Question 9

As Friedreich Ataxia progresses, what symptoms are unique?

Answer 9

Cardiomyopathies

– increased arrhythmias and congestive heart failure

Question 10

This spinocerebellar degeneration involves decreased DTRs but still (+) extensor plantar reflex

Answer 10

Friedreich Ataxia

Question 11

Patients with Friedreich Ataxia usually also have what condition?

Answer 11

Diabetes Mellitus

Question 12

When does Ataxia-Telangiectasia begin and what is the outlook for it?

Answer 12

Begins in childhood –> death by 2nd decade

Question 13

Ataxia-Telangiectasia involves telangiectasias where?

Answer 13

Conjunctiva, skin, CNS

Question 14

What gene is mutated with Ataxia-Telangiectasia and on what chromosome?

Answer 14

ATM gene on chromosome 11

Question 15

What is the ATM gene on chromosome 11 responsible for?

Answer 15

Response to double stranded DNA breaks

Question 16

Those with Ataxia-Telangiectasia fail to remove cells with?

Answer 16

Fail to remove cells with DNA damage

– mutated ATM gene that response to double stranded DNA breaks

Question 17

What will patients with Ataxia-Telangiectasia be very sensitive to?

Answer 17

X-rays

– cannot fix double stranded DNA breaks

Question 18

What is lost with Amyotrophic Lateral Sclerosis (ALS)?

Answer 18

Loss of upper and lower motor neurons!

Question 19

Loss of upper and lower motor neurons

Answer 19

Amyotrophic Lateral Sclerosis (ALS)

Question 20

What genes are associated with ALS development?

Answer 20

SOD1

TDP-43

Question 21

What genes are associated with ALS development?

Answer 21

SOD1

TDP-43

Question 22

What is decreased with ALS?

Answer 22

Decreased # of Anterior horn neurons

Question 23

This spinocerebellar degeneration involves thin anterior roots of the spinal cord and an atrophic precentral gyrus

Answer 23

ALS

Question 24

What cytoplasmic inclusions are present with ALS?

Answer 24

Bunina Bodies

Question 25

Due to LMN loss with ALS, what will occur?

Answer 25

Neurogenic atrophy of skeletal muscles

Question 26

Due to UMN loss with ALS, what will occur?

Answer 26

Degeneration of corticospinal tracts

Question 27

Decreased # of Anterior horn neurons and intracytoplasmic Bunina Bodies suggests?

Answer 27

Amyotrophic Lateral Sclerosis (ALS)

Question 28

What are the early symptoms of ALS?

Answer 28

Asymmetric hand weakness | --> dropping things/cramping

Question 29

As ALS progresses, what other symptoms will be seen?

Answer 29

Fasciculations and recurrent pneumonia | Deglutination and phonation difficulties (speaking and swallowing)

Question 30

First sign of ALS?

Answer 30

Dropping things/cramping in the hands asymmetrically

Question 31

What is 1 Neuronal storage disease?

Answer 31

Tay-sachs

Question 32

What gene is mutated with Tay Sachs?

Answer 32

HEXA

Question 33

What enzyme is deficient with Tay Sachs?

Answer 33

Hexosaminidase A

Question 34

What substrate accumulates in the neuron with Tay Sachs?

Answer 34

GM2 Gangliosides

Question 35

What is a physical exam finding with Tay Sachs?

Answer 35

Cherry red spots on the maculae