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20 Cards in this Set
- Front
- Back
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What is the genetic basis of cystic fibrosis?
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Autosomal recessive disorder
Common in the caucasian population Mutations in a single gene on chromosome 7 CFTR- chloride channels |
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What are the most common types of cystic fibrosis?
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Class II- improper folding, with failure to deliver CFTR protein to cell surface. DeltaF508 mutation.
Class III- gating defect. G551D mutation. |
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How is cystic fibrosis diagnosed in infants?
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Newborn screening
Meconium ileus Failure to thrive Nasal polyps Early diabetes Constipation Salty sweat, dehydration |
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How is cystic fibrosis diagnosed in adults?
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Bronchiectasis
Sinus infections Nasal polyps Pancreatitis Nutritional deficiencies Metabolic alkalosis, hypokalemia Male infertility Unexplained cirrhosis Early diabetes |
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What is the pathopysiology of CFTR dysfunction?
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Decreased chloride secretion from airway epithelial cells into lumen.
Sweat glands- inability to resorb chloride Airways- inability to secrete chloride and thickened mucous. |
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What is the pathophysiology of inflammation in cystic fibrosis?
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Early inflammatory response causes activated neutrophils to release proteases.
Large amounts of DNA increases viscosity. Abnormal flora increases respiratory infections. |
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What are pulmonary manifestations of cystic fibrosis?
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Cough
Bronchiectasis Hemoptysis Respiratory failure |
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What infections are common in cystic fibrosis?
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Early- staph aureus, H. influenza
Pseudomonas Late- Burkolderia cepacia |
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What bone abnormalities are found in CF?
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Inflammation stimulates bone resorption.
Malabsorption of Vitamin D, Vitamin K, calcium |
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What are GI manifestations of CF?
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GERD
Hepato-biliary disease Pancreatitis Intestinal obstruction |
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What current treatments are available for CF?
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Airway clearance
Antibiotics Oral steroids Anti-inflammatory therapy Mucolytics Gating correctors- ivacaftor |
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How was the CF gene cloned?
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Chromosomal walking used various probes to duplicate the gene and find the specific mutations on it.
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What residue was deleted in the deltaF508 mutation?
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Phenylalanine is lost, causing a defective protein.
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What is the function of the CFTR protein in a healthy person?
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Channel to guide chloride ions into the fluid of the respiratory tract. Balances with a sodium channel to balance. Sodium and chloride keep water at a certain level in the mucus.
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What is the molecular result of the CF defect?
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Lack of CFTR proteins being formed or transported to the surface results in deficiency of salt and water in the mucus.
Mucus builds up and leads to chronic infections. |
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What makes CFTR a good gene for replacement therapy? What are the challenges?
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Monogenic autosomal recessive disease, with only small amounts of functional CFTR protein needed.
However, thick mucus makes treatment difficult and host responses destroy vectors used. |
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How is kalydeco used to treat patients with G551 mutation?
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Potentiator to help the defective CFTR protein work better at the cell surface.
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What are alternative methods to treating CF?
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Na channel inhibitors
Activation of alternative Cl channels. Adding osmotically active agents to the lung |
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What new diagnostic methods are being discovered for CF?
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Allele-specific PCR
Polymorphism mapping of mutations Single strand conformation polymorphism mapping of mutations |
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How is VX-809 being used to treat deltaF508 mutation?
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Corrects folding defects in the CFTR protein.
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