Cystic Fibrosis in Children and Adults Flashcards
What type of inheritance is CF
Autosomal recessive
What is the gene prevalence of CF
1:25
Where does the CF gene lie
Long arm of chromosome 7
What does the CFTR gene do
Provides instructions for making a protein called the cystic fibrosis transmembrane conductance regulator that acts as a channel across membrane of cells that produce mucous, sweat, saliva, tears and digestive enzymes
How many known mutations are there and how many are associated with CF
> 2000
30
How many classes of mutations are there
6
Class I
No synthesis
G542X
Class II
Block in processing
F508del
Class III
Block in regulation
G551D
Class IV
Altered conductance
R117H
D1152H
Class V
Reduced synthesis
3849+ 10kbC –>T
5T
A455E
What is the most common mutation
Class II
phe508del
Functions of CFTR
Active transport of chloride
Regulates liquid volume on epithelial surface
Neonatal Screening for Cystic Fibrosis
Guthrie test (blood spot day 5) Screen positive referred for clinical assessment and sweat test
Diagnosis
Clinical assessment
Sweat test
Repeat CF mutation analysis
Why is there high Cl- in patients with CF
Dysfunctional CFTR channel that doesn’t allow ions to pass through
Why is there a pancreatic insufficiency in CF patients
Mucous build up can block the cells from secreting key compounds such as the nutrient and fat-metabolising enzymes from the pancreas
Antenatal screening (3)
Pre-implantation genetic diagnosis
Chorionic villus sampling
Amniocentesis
Management of CF (5)
Multi-organ disease Specialist MDT Primary care Surveillance Early treatment of infection
Two cardinal features of CF
Pancreatic insufficiency
Failure to thrive
What are the features of pancreatic insufficiency
Pale or orange stools
Very offensive
Greasy or oily
Treatment for pancreatic insufficiency (3)
Enteric coated enzyme pellets
High energy diet- low in fat
Fat soluble vitamin and mineral supplements
Cycle of CF lung disease (4)
Infection
Increased inflammation
Fibrosis/scarring/bronchiectasis
Mucous obstruction
Therapeutic targets for: Infection Increased inflammation Fibrosis/scarring/bronchiectasis Mucus obstruction
Antibiotics
Azithromycin
Airway clearance physiotherapy, Dornase alfa and hypertonic solution
Respiratory Pathogens in CF (2)
Staph. aureus
H. influenzae
Pre-infection precautions (6)
Segregation Airway clearance and adjuncts Mucolytics Prophylactic antibiotics Annual influenza vaccinations Reduce inflammation: Ibuprofen, Azithromycin, Prednisolone
CFTR modulator treatment (3)
Gene therapy
Gene editing
Triple combination therapy
Other complications (GI)
Dysmotility Meconium ileus Gastro-oesophageal reflux Distal intestinal obstruction Constipation/rectal prolapse Crohn's Coeliac
Other complications (8)
Hepatopathy Upper airway polyps and sinusitis Diabetes Osteopenia Arthropathy Heat exhaustion Bilateral absence of vas deferens Vaginal candidiasis
Fertility Issues (2)
Puberty may occur later
Men- blocked or absent vas deferens
Male fertility issue options (3)
Adoption
Artificial insemination
Intra-cytoplasmic injections
Lung transplant issues (2)
last resort treatment
Not miracle cure
Severe patients experience (5)
FEV1 <30% Weight loss Hypoxia Hypercapnia Recurrent worsening sepsis
Contra-indications for lung transplant (9)
Organ failure Malignancy within 5 years Peripheral vascular disease Drug, nicotine or alcohol dependency Active systemic infection Steroids >20mg Osteoporosis Low BMI Surgical risks
