CF Flashcards
What is the most common gene mutation in cystic fibrosis?
Mutations occur in a single large gene on chromosome 7 that encodes for the CFTR protein. Delta F 508 is the most common mutation - deletion of 3 DNA bases coding for the 508th amino acid. 50% homozygous, 40% heterozygous
What is the diagnostic test for CF?
Chloride sweat test >60mmol,
Genetic testing
Abnormal nasal potential difference
What is the inheritance of CF?
Autosomal recessive - clinical disease requires disease causing mutations in both copies of the CFTR gene.
What is the genetic defect that causes CF?
mutations in the Cystic Fibrosis transmembrane conductance regulator (CFTR) protein. This is a chloride channel and regulatory protein found in all exocrine tissues.
What are the 5 classes of mutations and their significance?
Class 1 - no synthesis
Class 2 - blick in processing, missense amino acid deletion - (delatF508)
CLass 3 - block in regulation, missense amino acid change (G551D)
Class 4 - Altered conductance, missense amino acid change (R117H, R347P)
CLass 5 - reduced synthesis, Missense amino acid change (A445E), alternative splicing
- in general classes 1-3 cause more severe disease than 4,5
What is the consequence of the derange CFTR protein in CF?
abnormal transport of chloride results in thick, viscous secretion in the lungs, pancreas, liver, intestines and reproductive tract.
What are the GIT complications of CF?
impaired flow of bile and pancreatic secretions - malabsor[tion and maldigestion.
Liver and pancreatic disease leads to CF diabetes.
Prone to intestinal obstruction and rectal prolapse
What are the pulmonary complications of CF?
chronic airway obstruction by thick secretions
colonisation by bacteria
- H. influenza
- Staph. aureus
- Pseudomonas
- Burkholderia cepacia
Bronchiectasis due to chronic inlammation
When is Ivakaftor indicated?
Mutations: G551D also R117H, G1244E, G1349D, G178R, G551S, S1251N, S1255P, S549N, or S549R
What long-term antibiotic has been shown to improve lung function in CF colonised by pseudomoas?
Azithromycin used 3 times a week
What are the goals of CF therapies?
Maintain lung function, maintain growth, manage complications
What infections are associated with a worse prognosis post lung transplant?
Burkolderia cepacia - higher 6 month mortality
Mycobacterium abscessus
Effects of CF on fertility?
95% of males azoospermic due to obliteration of vas deferns
20% of females infertile due to thick cervical mucus and effect of chronic illness on menstruation
What is the carrier rate of the CF mutation?
1 in 25 in northern europeans and NZ and australia
What is the incidence of CF?
1 in 3000 births
- less in asian populations 1 in 9000
