Lecture 25: Clinical context of screening Flashcards
What is cystic fibrosis?
Mutation in the CFTR gene which results in its inability to transport Cl- ions this secretions are thick and mucous like (very little water) and it is very hard to clear
How are newborns tested for CF?
- Measure blood trypsin (pancreatic enzyme) as pancreas cant secrete b/c hyper-viscous mucous, these enzymes are then absorbed.
- If this enzyme is high then genetic analysis for the three common CF genes (/54)
Is CFTR disfunction always the same?
No many genetic variations
- No protein (classical)
- No protein trafficking
- No function
- Less function
- Less protein
- Less stable
Thus phenotype varies.
What are the steps following the positive newborn screening test?
Screening doesnt mean diagnosis
1) Sweat test (Cl-)
2) Genetics test (52 genes)
3) Stool sample (looking for pancreatic enzymes, indicative of severity, no enzymes = severe)
What can be the outcome of CF for an infant?
Prominently
- Recurrent pneumonias -> Progressive lung disease
- Failure to thrive/poor growth
What is the management for CF?
- History
- Growth tracking
- Physical examination
- Cough
- Chest deformity
- Oxygen sats
- Radiology (regularly)
- Lung function tests
Whats the treatment for CF?
- Respiratory
- Nutrition
- Other - now including specific gene therapies
How can respiratory function be treated in CF?
- Chest physiotherapy to clear airways
- Exercise (promotes lung growth)
- Antibiotics, (because increased bacteria)
How can nutrition be used as a treatment in CF?
- Enzyme replacement
- Vitamin supplementation
- Salt supplementation
- High calorie diet
- Supplements
- Gastrostomy feeds
What drug opportunities are there for CF?
Correctors (corrects protein deficits)
Potentiators (improves opening of CFTR channel)
How has life expectancy and lung function changed over time?
Treatments today better preserve lung function and increase life expectancy in those with CF
What is cascade testing?
Calculating the carrier risk for other relatives by working through the generations
note: children are only tested when they are adults as they can decide only then if they want to know (this is for carrier status)
What is preimplantation genetic testing?
Embyro is biopsied, ~5 cells are taken and transferred to an unaffected embyro
- See how they cope
- genetically test all aspects of genome
How else can you test a pregnancy?
Non-invasive prenatal diagnosis (NIPD)
What is NIPD?
Non-invasive prenatal diagnosis uses circulating cell-free fetal DNA (cffDNA) in the maternal plasma to test for a known genetic disease in a family by relative haplotype dosage analysis. (examining SNPs that flank the disease gene).
Note this was covered in an earlier lecture and flash cards
