Cystic fibrosis

Most common lethal genetic disorder

   

Defect: mutation of the chloride channel protein, cystic fibrosis trans-membrane conductance regulator (CFTR)

Genetics

  

i. CFTR gene is located on chromosome 7

ii. Most common mutation is a deletion in amino acid position 508 (AF508)

Pathogenesis: 

• defective chloride channel protein leads to abnormally thick viscous mucous, which obstructs the ducts of exocrine organs

Distribution of disease

i. Lungs

• Recurrent pulmonary infections with P. aeruginosa and S. aureus . 
• Chronic bronchitis
• Bronchiectasis

ii. Pancreas

•  Plugging of pancreatic ducts results in atrophy and fibrosis
•  Pancreatic insufficiency
•  Fat malabsorption 
•  Malodorous steatorrhea
•  Deficiency of fat-soluble vitamins

iii. Male reproductive system

• Obstruction of the vas deferens and epididymis
• May lead to male infertility

 iv. Liver:

•  plugging of the biliary canaliculi may result in biliary cirrhosis

v. GI tract:

• small intestinal obstruction (meconium ileus)

Diagnosis

i. Sweat test (elevated NaCl)
ii. DNA probes

Treatment

• Chest Physiotherapy
• Antibiotics
• Mucolytics : N-acetylcysteine
• Gene therapy

Prognosis
i. Mean survival: 30 years
ii. Most common cause of death is pulmonary infections