Cystic Fibrosis

Question 1

What systems does it affect most?

Answer 1

digestive, sweat glands, reproductive tract, lungs

Question 2

Major cause of Morbidity and Mortality

Answer 2

progressive lung disease

Question 3

How many genes and what chromosome

Answer 3

single gene, chromosome 7

Question 4

What does chromosome 7 encode?

Answer 4

CF trans-membrane conductance regulator

(CFTR) protein

Question 5

Which endocrine system does it affect?

Answer 5

Exocrine

Question 6

Dominant or Recessive?

Answer 6

Autosomal recessive

Question 7

CFTR protein

Answer 7

regulates volume and composition of exocrine secretion

Question 8

How many different mutations are listed?

Answer 8

more than 1900

Question 9

What is the most common mutation?

Answer 9

delta F508 (CLASS II)
-- found in 70% of Caucasian CF patients

Question 10

Why is it found in higher frequency in certain ethnic groups?

Answer 10

Founders effect

Question 11

How many classes of the disease?

Answer 11

5

Question 12

What classes cause the most severe disease?

Answer 12

mutations in classes I-III

Question 13

Defective protein production is class…

Answer 13

…1

Question 14

Class I Mutation

• caused by
• leads to

Answer 14

• Caused by nonsense, frame-shift or splice-site mutations

- Leads to premature termination of the mRNA

Question 15

Founders Affect

• what pop and how frequent
• what kind of mutation

Answer 15

• 60% of Ashkenazi Jews

- nonsense mutation

Question 16

Class II Mutation

• caused by
• leads to

Answer 16

• deltaF508

- prevents protein from trafficking to the correct cell location

Question 17

deltaF508

Answer 17

class II
50% CF pts homozyg. for the deletion 
90% are heterozyg.

Question 18

Class III

Answer 18

Limited response to ATP

Question 19

Class IV

Answer 19

rate of ion flow and duration of channel opening are reduced compared to normal function of the protein

Question 20

Class V

Answer 20

reduced amount of the CFTR protein

can also alter stability of the mature protein

Question 21

Gene Modifiers

Answer 21

• causes inconsistent associations between CF geno and phenotypes
• not directly related to CFTR gene but affect the clinical manifestations

Question 22

Gene modifier evidence

Answer 22

20% pts with classic CF carry modifiers that exacerbates the pulmonary disease

Question 23

Mannose-binding lectin protein

Answer 23

• a gene modifier
• important component of complement system
• when deficient, increases risk for infections with fevers
• risk for Burkholderia cepacia infections and early death

Question 24

TGF-beta 1

Answer 24

• transforming growth factor-beta
• suppressor of T-cell activation
• associated with the most severe cases of CF

Question 25

How long to pts survive?

Answer 25

Highly varriable

Question 26

Chronic...

Answer 26

infections of the respiratory tract

Question 27

Mild?

Answer 27

10% pts have unusually mild sx

Question 28

immunoreactive trypsinogen test

Answer 28

- checks for immunoreactive trypsinogen chemical made by the pancreas - when pancreas is stressed when a baby is born, more of this chemical is made - can be high if premature or has CF

Question 29

Gibson-Cooke

Answer 29

gauze that collects sweat in chloride sweat test

Question 30

Chloride Sweat Test

Answer 30

value > 60 = CF - 20% of children with middle results have DNA evidence of CF - children with ambiguous results have (+)sweat test and some sx but not entire disease

Question 31

Classic CF

Answer 31

diagnosed if in one or more organ systems

Question 32

Non-classic

Answer 32

- likely in pts first diagnosed as adults | - lower frequency of delta F508 mutation

Question 33

Survival rate

Answer 33

36.8 years

Question 34

Signs and Sx

Answer 34

- persistant pulmonary infections - pancreatic insufficiency - elevated sweat chloride levels

Question 35

Staph. aureus Haemophilus flu pseudomonas aeruginosa

Answer 35

common flora found in CF cultures

Question 36

burkholderia cepacia complex

Answer 36

- bacteria that indicates significant disease and that pt is declining - accelerated decline in pulmonary function and shortened survival - contraindication to transplantation

Question 37

Tenacious exocrine secretions

Answer 37

obstruct pancreatic ducts and impair production and flow of digestive enzymes to duodenum

Question 38

Pancreatic effects

Answer 38

loss of islet cell mass= CF-related diabetes mellitus | -30% of adults

Question 39

Hepatic Effects

Answer 39

Multilobular cirrhosis in 4-15% of pts

Question 40

Intestinal Effects

Answer 40

10-20% of newborns with CF have meconium ileus

Question 41

Pediatric CF

Answer 41

- infants presenting with meconium ileus diagnosed within the first two weeks - others diagnosed around 14.5 months

Question 42

Reproductive effects

Answer 42

secretory obstruction of the vas deferens | -1/2 of men with bilateral absence of vas deferens have 2 CFTR mutations

Question 43

DNA test - what results should be checked? - what how many mutations do labs test for?

Answer 43

intermediate sweat test results should be clarified by DNA using a CFTR multi-mutation method - most labs in US test for 23 mutations - California does 40

Question 44

CF confirmed other ways?

Answer 44

- 2 CF causing mutations detected | - sweat test intermediate or positive

Question 45

CRMS

Answer 45

CFTR-related metabolic syndrome

Question 46

Nasal Potential Difference Measurements

Answer 46

test that shows abnormalities in epithelial chloride secretion

Question 47

pseudomonas aeruginosa

Answer 47

CF pts are particularly susceptible to this bacterial infection and can happen as early as the first year of life

Question 48

Staphylococcus

Answer 48

bacteria most frequently identified in CF secretions from children and infants