Lecture 25- Integrated Approach to a genetic disorder: Cystic Fibrosis Flashcards Preview

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Screening process

Heal prick done after birth
20+ metabolic disorders tested, 45babies/year found. Info goes to midwife.


Cystic Fibrosis

CF is inherited in an autosomal recessive manner. It is caused by the presence of mutations in both copies of the gene for the cystic fibrosis transmembrane conductance regulator (CFTR) protein. This is a chloride channel involved in mucus formation. When mutated the Cl can't leave the cell, so Na+ and therefore water also remains> thick sticky mucus


New born screening for CF

1) Blood test for trypsin (pancreatic enzyme): Thick secretions 1st block pancreatic duct, enzymes can't move into GI tract and will instead by found in the blood stream

2) if high > three common CF genes


Family have had first baby Zak, get a letter that their baby has CF/is a carrier. What do they wan't to know?

Does he has disease or is he a carrier?
What is CF?
What will happen?
Can he be treated?


If Zak is positive on the newborn screen, the next testing steps are..

1) Sweat test: Much higher NaCl levels

2) Zak's genetics: for any issues, more specific mutations, double checking he does have CF

3) Stool sample for enzymes: look for trypsin, if not there we immediately start enzyme supplementation so he can digest food


What are issues Zak is going to have to face?

Most common:
Recurrant pneumonia > progressive lung disease
Failure to thrive/poor growth (pancreatic issues)

Other potential Issues all due to thick sticky mucus:

-nasal polyps
-gall stones
-portal hypertension


Management of Zaks CF includes

1: History
2: Growth and height
3: Physical signs; chest deformity & finger clubbing

Regular auscultation

Respiratory testing: Oxygen saturation, lung function

Radiology: CT scans, ultrasounds

Check for infection: swabs, mucus, bronchoscopy


Infection risk is common

staph, pseudomonas aeruginosa is common

these change with age


Treatment is centered around

1) Respiratory issues
2) Nutrition Issues
3) Other that may show up


Types of treatment

physiotherapy: to strengthen lungs/clear mucus. kids get tired of it


Antibiotics: nebulised (high levels in lungs), oral

Growth & nutrition: Enzyme replacement from birth, and vitamin replacement.
Need a high calorie diet, sometimes gastrostomy feeding required (tube straight to stomach)

Treatment requires huge daily effort/undertaking, strenuous on patient.

It is working, as life expectancy hugely increasing every year.


First Genetic counselling appointment

Review diagnosis, ask questions (many on inheritance), talk about the future
-having more kids
-impact on family (siblings wanting kids)

Testing arranged (check both parents are carriers AR disorder)

Check to see how they are managing



Things to Consider for the family

With Genetic Testing
-Important to know which mutation from which side
-but may inadvertantly reveal family relationships
-they need to have the ability to give consent for the testing (informed, for kids a direct benefit for testing is required, who can have access to results)

Distress with diagnosis/loss of 'perfect' child

Feelings of guilt for 'giving this' to their child


Family Planning

-Can be extremely difficult and distressing

Options are to....
not have more kids, have kids with no more testing, a sperm donor, prenatal testing (CVS and amniocentesis), pre-implantation genetics with IVF

Decisions influenced by ethical, religious beliefs, views on sickness and disability, treatment availability/efficiency, availability of social and financial support for the family.


Pre-implantation genetic diagnosis with IVF

couples who are eligible can access upto 2 publicaly funded cycles
Criteria: woman under 40, BMI


why is pregnancy not accurate

no eggs recovered
no viable embryos
results not 100% accurate
risk of miscarriage
chromosomal abnormalities can occur



If couple want PGD
refered to fertility service, put on waitlist

If couple get pregnant naturally
referral to maternal fetal medicine
-do genetic testing


Testing the pregnancy. Is the fetus affected?

Why may they be doing this?
-previous child with a condition
-family history of a condition
-abnormality on a pregnancy scan
-just really concerned, many parents just want to know


We need DNA to test to get answers for parents

DNA from tissue 'invasive test'
Trophoblast- early placenta
fetal cells - fibroblasts in amniotic fluid

also DNA from maternal plasma


Trophoblast (part of placenta)

Chorionic Villus Sampling (CVS)

DNA from CV ~12wks (suck themout with needle)

earlier in pregnancy
direct DNA extraction

Technically more difficult then amniocentesis
Maternal cell contamination ~1% samples




Done later in pregnancy
takes longer as you have to grow cells



no miscarriage risk
Simpler less stressful
preperation for affected