Degenerative Diseases part 2 Flashcards
Where is the dysfunction with Spinocerebellar Degenerations?
Cerebellum
Spinal cord
Peripheral nerves
Spinocerebellar Ataxias are a group of disorders that involve spinocerebellar degenerations. How are they inherited and what gene mutation is involved?
Autosomal Dominant inheritance
– SCA mutations
What are 3 Spinocerebellar Degenerations?
- Friedreich Ataxia
- Ataxia-Telangiectasia
- Amyotrophic Lateral Sclerosis
What are 3 Spinocerebellar Degenerations?
- Friedreich Ataxia
- Ataxia-Telangiectasia
- Amyotrophic Lateral Sclerosis
What trinucleotide repeat is present with Friedreich Ataxia?
GAA
With Friedreich Ataxia, what protein is decreased?
Frataxin
What presents in the 1st decade of life with Friedreich Ataxia?
Gait ataxia
As Friedreich Ataxia progresses, what symptoms are unique?
Cardiomyopathy
– increased arrhythmias and congestive heart failure
As Friedreich Ataxia progresses, what symptoms are unique?
Cardiomyopathies
– increased arrhythmias and congestive heart failure
This spinocerebellar degeneration involves decreased DTRs but still (+) extensor plantar reflex
Friedreich Ataxia
Patients with Friedreich Ataxia usually also have what condition?
Diabetes Mellitus
When does Ataxia-Telangiectasia begin and what is the outlook for it?
Begins in childhood –> death by 2nd decade
Ataxia-Telangiectasia involves telangiectasias where?
Conjunctiva, skin, CNS
What gene is mutated with Ataxia-Telangiectasia and on what chromosome?
ATM gene on chromosome 11
What is the ATM gene on chromosome 11 responsible for?
Response to double stranded DNA breaks
Those with Ataxia-Telangiectasia fail to remove cells with?
Fail to remove cells with DNA damage
– mutated ATM gene that response to double stranded DNA breaks
What will patients with Ataxia-Telangiectasia be very sensitive to?
X-rays
– cannot fix double stranded DNA breaks
What is lost with Amyotrophic Lateral Sclerosis (ALS)?
Loss of upper and lower motor neurons!
Loss of upper and lower motor neurons
Amyotrophic Lateral Sclerosis (ALS)
What genes are associated with ALS development?
SOD1
TDP-43
What genes are associated with ALS development?
SOD1
TDP-43
What is decreased with ALS?
Decreased # of Anterior horn neurons
This spinocerebellar degeneration involves thin anterior roots of the spinal cord and an atrophic precentral gyrus
ALS
What cytoplasmic inclusions are present with ALS?
Bunina Bodies
Due to LMN loss with ALS, what will occur?
Neurogenic atrophy of skeletal muscles
Due to UMN loss with ALS, what will occur?
Degeneration of corticospinal tracts
Decreased # of Anterior horn neurons and intracytoplasmic Bunina Bodies suggests?
Amyotrophic Lateral Sclerosis (ALS)
What are the early symptoms of ALS?
Asymmetric hand weakness
–> dropping things/cramping
As ALS progresses, what other symptoms will be seen?
Fasciculations and recurrent pneumonia
Deglutination and phonation difficulties (speaking and swallowing)
First sign of ALS?
Dropping things/cramping in the hands asymmetrically
What is 1 Neuronal storage disease?
Tay-sachs
What gene is mutated with Tay Sachs?
HEXA
What enzyme is deficient with Tay Sachs?
Hexosaminidase A
What substrate accumulates in the neuron with Tay Sachs?
GM2 Gangliosides
What is a physical exam finding with Tay Sachs?
Cherry red spots on the maculae
