Cystic Fibrosis Flashcards
What is cystic fibrosis (CF)?
Autosomal recessive genetic condition that results in a multisystem syndrome of chronic sinopulmonary infections; malabsorption; and nutritional abnormalities. Most common life-shortening genetic disease in Caucasians in the US (1:3000)
Which chromosome mutation causes CF?
Gene that encodes for the CF transmembrane conductance regulator (CFTR) protein. On Chr. 7. Causes a deft in the ATP-binding cassette transporter gene
What is the most common mutation?
F508del. But there are more than 1500 others identified
How are CF gene mutations categorized?
5 main classes (I-V). Grouped by molecular consequences.
What is a class I mutation?
No synthesis of CFTR. Often caused by nonsense G542X
What is a class II mutation?
Block in CFTR synthesis. Often caused by AA deletion (F508del)
What is a class III mutation?
Block in gating. Often caused by missense G551D
What is a class IV mutation?
Altered conductance of CFTR. Often caused by missense R117H
What is a class V mutation?
Reduced synthesis of CFTR. Often caused by missense mut or alternative splicing
What effects do defects/deficiences of CFTR proteins cause?
Problems in salt and water movement across cell membranes; resulting in abnormally thick secretions in various organ systems
Why are CFTR effects in lungs often major cause of morbidity and mortality?
Depleted periciliary layer in the lung leads to impaired mucociliary clearance and altered host defense; critical to the pathogenesis of CF lung disease. Chronic infections with CF-related pathogens and excessive inflammatory response progressively damage the airways and lung parenchyma. Results in widespread bronchiectasis; decline in lung function; early death from respiratory failure
What are typical clinical features in sinus?
Chronic sinus infections; nasal polyps
What are typical clinical features in lung?
Recurrent respiratory infections (endobronchitis) with opportunistic bacteria (e.g. Staphylococcus aureus; Pseudomonas aeruginosa and Burkholderia cepacia); Bronchiectasis
What are typical clinical features in pancreas?
Exocrine pancreatic insufficiency (85%) - greasy; bulky; malodorous stools; failure to thrive and malabsorption nutritional consequences; CF-related diabetes
What are typical clinical features in GI?
Meconium ileus; rectal prolapse; constipation; distal ileal obstructive syndrome (DIOS)