Microbiology 4s: Prion Disease

Question 1

What is a prion?

Answer 1

Misfolded proteins with the ability to transmit their misfolded shape onto normal variants of the same protein.

• They do contain DNA, but they are only made of protein

Question 2

What happens when prions enter the brain?

Answer 2

• When they enter the brain, they can trigger a cascade where existing prion proteins become rapidly affected and develop the abnormal isoform of the prion protein
• → spongiform vacuolisation of the brain
• → rapid neurodegeneration

Question 3

What is the curative Tx for prion disease?

Answer 3

• no curative Tx
• palliative care (see later for Txs)

Question 4

Is there a prion protein gene?

Answer 4

Question 5

What are the polymorphisms found on codon 129 (Chr 20)

Answer 5

On Codon 129 there are THREE polymorphisms that we can find:

• MM– predisposes to prion disease
• MV
• VV

M=Methionine

V=Valine

Question 6

What is the protein structure of prion protein?

Answer 6

sc = scrapie isoform of the prion protein

Question 7

How do prion replicate?

Answer 7

like dominos!

Question 8

How is prion disease classified?

Answer 8

Question 9

Epidemiology and prognosis of sporadic CJD?

Answer 9

• Epidemiology:
  
  • Incidence: 1/million/year
  • mean age: 65yrs
• prognosis:
  
  • death within 6 months

Question 10

Cause of sporadic CJD?

Answer 10

Cause is uncertain; could be due to…

• Somatic PRNP mutation
• Spontaneous conversion of PrP to PrPSc
• Environmental exposure to prions

Question 11

Signs & symptoms of sporadic CJD?

Answer 11

Question 12

Ix for diagnosis of sporadic CJD?

Answer 12

Question 13

brain histology. What does it show?

Answer 13

spongiform vacuolation (sporadic CJD)

Question 14

brain histology. What does it show?

Answer 14

amyloid plaques (sporadic CJD)

Question 15

DDx for sporadic CJD?

Answer 15

Question 16

Variant CJD clinical picture & prognosis?

Answer 16

Question 17

Ix for variant CJD diagnosis?

Answer 17

Question 18

Causes of iatrogenic CJD?

Answer 18

• Human cadaveric growth hormone
• Neurosurgical procedures (e.g. corneal grafts)
• Other surgical procedures (e.g. appendicectomy, tonsillectomy)
• Corneal transplants
• Blood transfusions

Question 19

Clinical features of iatrogenic CJD?

Answer 19

• Progressive ataxia → dementia and myoclonus
• Speed of progression depends on route of inoculation (CNS inoculation is the fastest)

Question 20

Summarise the genetics of prion disease

Answer 20

• Codon 129 MM polymorphism (MM confers increased risk – more so than MV and VV)
  
  • (sporadic prion disease)
• Specific PRNP mutations (~30 so far) – all autosomal DOMINANT
  
  • (familial prion disease)

Question 21

Name some familial prion disease

Answer 21

• Gerstmann-Straussler-Sheinker syndrome
• Familial Fatal Insomnia

Question 22

What is important to ask for in FHx when considering familial prion disease?

Answer 22

Question 23

How is diagnosis of familial prion disease made?

Answer 23

Question 24

Summarise Gerstmann-Straussler-Sheinker Syndrome

Answer 24

Question 25

Summarise Fatal Familial Insomnia

Answer 25

Question 26

Summarise kuru

Answer 26

Question 27

Tx of prion disease?

Answer 27