Makindo Medical Notes.com

Related Subjects: |Osteoporosis |Malabsorption |Bronchiectasis |Pseudomonas infection (Pseudomonas aeruginosa) |Autosomal Recessive |Genetic Mutations |Clustered Regularly Interspaced Short Palindromic Repeats CRISPR

Disease presents without warning and some forms milder than others. A sweat chloride concentration of 80 mmol/l is diagnostic. A person with CF cannot contract cholera, because the toxin cannot open the chloride channels in the small intestine. With improved supportive care, the median survival in the UK is now more than 50 years.

Curbed flows of chloride
Lung’s massed mucus, thick and dried
Bad bugs stick and thrive
Body’s small tubes have it worst
Baby gut often blocked first
@DrCindyCooper

About

• Inherited Defect of the Cystic fibrosis transmembrane conductance regulator (CFTR)
• Leads to the production of thick viscid mucus and secondary infection

Aetiology

• CF is inherited as an AR and there are at least 800 gene mutations
• Mutation in cystic fibrosis transmembrane conductance regulator (CFTR) gene on 7q31.2.
• Genotype is a poor guide to disease severity even within families possibly due to unknown modifier genes
• Over 70% are due to the delta F508 mutation on chromosome 7q which codes for the CFTR
• Incidence in the UK is 1 in 2500 and life expectancy for teenagers is 40-50 years old

Gene Mutations and effects

Diagnosis

• Positive test results in people with no symptoms, for example infant screening (blood spot immunoreactive trypsin test) followed by sweat and gene tests for confirmation or
• clinical manifestations, supported by sweat or gene test results for confirmation or
• Clinical manifestations alone, in the rare case of people with symptoms who have normal sweat or gene test results.

Clinical Gastrointestinal

• Failure to thrive and Malabsorption
• Meconium ileus - intestinal obstruction at birth
• Meconium ileus equivalent later
• Gallstone ileus and gallstone related disease
• Pancreatic insufficiency - steatorrhoea, weight loss
• Increased incidence of cholecystitis and gallstones
• Fatty liver and focal biliary cirrhosis
• Secondary Diabetes develops in 25% of patients
• Rectal prolapse

Pulmonary

• Normal lungs become progressively damaged
• Recurrent chest symptoms - infections, bronchiectasis
• Pneumothorax - seen mainly in adults
• Massive haemoptysis, Bronchitis, bronchiolitis, Bronchiectasis
• Eventual Respiratory failure, Rhinitis and nasal polyps
• Overtime increasing Pseudomonas infection
• Respiratory infections: Staphylococcus aureus, Haemophilus influenzae, Pseudomonas aeruginosa

Others

• Finger clubbing and Nasal polyps and sinusitis
• Circulating immune complexes and amyloidosis
• Male infertility - Failure to develop epididymis and vas deferens
• Osteoporosis and rickets
• Infant's sweat tastes salty - may be noted by parent

Carriers of CF enjoy the mixed blessing of a balanced polymorphism. They do not have enough abnormal chloride channels to cause the laboured breathing and clogged pancreas of cystic fibrosis, but they do have enough of a defect to prevent cholera from taking hold. During the devastating cholera epidemics that have peppered history, individuals carrying mutant CF alleles had a selective advantage, and they disproportionately transmitted those alleles to future generations. However, because CF arose in Western Europe and cholera in Africa, perhaps an initial increase in CF heterozygosity was a response to a different diarrheal infection

Investigations

• Immunoreactive trypsinogen is elevated in new-borns. This will need a sweat test if positive
• Sweat test: CF is diagnosed by clinical suspicion followed by a sweat test using Pilocarpine iontophoresis. If the sweat [Cl] or [Na] > 60 mmol/l then the test is considered positive. Two reliable positive sweat tests with a chloride concentration > 60 mmol/l is considered to be diagnostic
• DNA analysis may be done but with a large number of mutations is not needed
• Pancreatic insufficiency - faecal elastase, ? faecal fats, ? glucose with secondary diabetes
• USS testes may show an absent vas deferens and epididymis
• Establish baseline respiratory function testing

Summary of testing for CF

Complications

• Being underweight
• Meconium ileus (affects 1 in 7 newborn babies)
• Fat-soluble vitamin deficiencies (including vitamins A, D, E and K)
• Distal intestinal obstruction syndrome
• Muscle pains and arthralgia
• Male infertility caused by obstructive azoospermia (almost all males with cystic fibrosis are infertile)
• Reduced female fertility
• Upper airway complications, including nasal polyps and sinusitis (prevalence increases with age)
• Chronic liver disease (the prevalence increases with age until early adulthood)
• Urinary stress incontinence
• Cystic-fibrosis-related diabetes (uncommon in children under 10 years, but the prevalence increases with age and it affects up to 1 in 2 adults)
• Reduced bone mineral density (including osteoporosis).
• Cystic-fibrosis-related arthritis
• Delayed puberty (associated with severe cystic fibrosis)
• Renal calculi (incidence increases with age and 1 in 20 adults are affected).

Management

References

• NICE guidance on CF