Cystic fibrosis(genetic disease)

understanding Cystic fibrosis(genetic disease).

1. Cystic fibrosis(genetic disease) Presented by- Vl -a M.Sc Department of biotechnology Central Mizoram university

2. Outline What is cystic fibrosis (CF)? What causes CF? What are the manifestations? How do you diagnose CF? How do you treat CF?

3. Cystic Fibrosis Inherited monogenic disorder presenting as a multisystem disease. Typically presents in childhood 7% of CF patients diagnosed as adults Most common life limiting recessive trait among whites

4. Cystic Fibrosis Prognosis improving >38% of CF patients are older than 18 13% of CF patients are older than 30 Median survival Males: 32 years Females: 29 years

5. Genetics of CF Autosomal recessive Gene located on chromosome 7 Prevalence- varies with ethnic origin 1 in 3000 live births in Caucasians in North America and Northern Europe 1 in 17,000 live births of African Americans 1 in 90,000 live births in Hawaiian Asians

6. Genetics of CF Most common mutation Occurs in 70% of CF chromosomes 3 base pair deletion leading to absence of phenylalanine at position 508 ( D F 508 ) of the CF transmembrane conductance regulator (CFTR) Large number (>1000) of relatively uncommon mutations.

7. Genetics of CF D F 508 mutation leads to improper processing and intracellular degradation of the CFTR protein Other mutations in the CF gene produce fully processed CFTR proteins that are either non-functional or partially functional

8. Mutation of CFTR

9. Normal airway epithelia CF altered airway epithelia

10. Pathophysiology Lung High rate of sodium absorption and low rate of chloride secretion reduces salt and water content in mucus, depletes peri-ciliary liquid Mucus adheres to airway surface, leads to decreased mucus clearing Predisposition to Staph and Pseudomonas infections

11. Pathophysiology Gastrointestinal Biliary tree Retention of biliary secretion Focal biliary cirrhosis Bile duct proliferation Chronic cholecystitis, cholelithiasis Sweat Normal volume of sweat Inability to reabsorb NaCl from sweat as it passes through sweat duct

12. Pathophysiology Gastrointestinal Biliary tree Retention of biliary secretion Focal biliary cirrhosis Bile duct proliferation Chronic cholecystitis, cholelithiasis Sweat Normal volume of sweat Inability to reabsorb NaCl from sweat as it passes through sweat duct

13. Manifestations Genitourinary Late onset puberty Due to chronic lung disease and inadequate nutrition >95% of male patients with CF have azospermia due to obliteration of the vas deferens 20% of female patients with CF are infertile >90% of completed pregnancies produce viable infants

14. Diagnosis DNA analysis not useful due to large variety of CF mutations Sweat chloride test >70 mEq/L 1-2% of patients with clinical manifestations of CF have a normal sweat chloride test Nasal transepithelial potential difference

15. Diagnosis Criteria One of the following Presence of typical clinical features History of CF in a sibling Positive newborn screening test Plus laboratory evidence for CFTR dysfunction Two elevated sweat chloride concentrations on two separate days Identification of two CF mutations Abnormal nasal potential difference measurement

16. Treatment Major objectives Promote clearance of secretions Control lung infection Provide adequate nutrition Prevent intestinal obstruction Investigation into therapies to restore the processing of misfolded CFTR protein

17. Treatment Lung >95% of CF patients die from complications of lung infection Breathing exercises Flutter valves Chest percussion ? Hypertonic saline aerosols

18. Treatment Lung Atelectasis Chest PT + antibiotics Respiratory failure and cor pulmonale Vigorous medical management Oxygen supplementation Only effective treatment for respiratory failure is lung transplantation 2 year survival >60% with lung transplatation

19. Treatment Gastrointestinal Pancreatic enzyme replacement Replacement of fat-soluble vitamins- especially vitamin E & K Insulin for hyperglycemia Intestinal obstruction Pancreatic enzymes + osmotically active agents Distal- hypertonic radiocontrast material via enema

20. Treatment Gastrointestinal End-stage liver disease- transplantation 2 year survival rate >50% Hepatic and gallbladder complications treated as in patient without CF

21. Summary CF is an inherited monogenic disorder presenting as a multisystem disease Pathophysiology is related to abnormal ion transportation across epithelia Respiratory, GI and GU manifestations Treatment is currently preventative and supportive

22. REFERENCE: Collin F.S(2006) Cystic fibrosis National Library of Medicine 2008,Cystic Fibrosis The Nemours Foundation 2008,Cystic fibrosis,accessed on 18 Aug ,2009 Genetic Sciences Learning Center 2009,Cystic fibrosis,accessed on 18 Aug ,2009

23. THANK YOU…….