Cystic Fibrosis (CF)

also called MUCOVISCIDOSIS, formerly CYSTIC FIBROSIS OF THE PANCREAS, an inherited recessive disorder, the chief symptom of which is the production of a thick, sticky mucus that clogs the respiratory tract and the gastrointestinal tract.

Cystic fibrosis is the most common inherited disorder affecting people of European ancestry. It is estimated to occur in 1 per 2,000 live births in these populations and is particularly concentrated in people of northwestern European descent. It is much less common among people of African ancestry (about 1 per 17,000 live births) and is very rare in Asiatics. The disorder was long known to be recessive--i.e., only persons inheriting a defective gene from both parents will manifest the disease. The disease has no manifestations in heterozygotes--i.e., those individuals who have one normal copy and one defective copy of the particular gene involved. When both parents are heterozygous, however, they may expect that, on the basis of chance, one out of four of their offspring will have the disease. In 1989 the defective gene responsible for cystic fibrosis was isolated; the gene lies in the middle of chromosome 7. This discovery raised the possibility of a screening test to identify those people (heterozygotes) who unknowingly carry the defective gene and may pass it on to their offspring.

Cystic fibrosis affects the functioning of the body's epithelia cells and exocrine glands--e.g., the mucus-secreting and sweat glands. In persons affected with the disease, the normal mucous secretions in the respiratory and digestive systems become abnormally thick, sticky, and concentrated. The defect (or mutation) found in the gene on chromosome 7 of persons with cystic fibrosis causes the production of a protein (CFTR) that lacks the amino acid phenylalanine at position 508. This mutated CFTR, a Cl- channel, no longer facilitates the movement of salt and water across the epithelial cell membranes that line the lungs and gut, resulting in dehydration of the mucus that normally coats these surfaces. The thick, sticky mucus accumulates in the lungs, plugging the bronchi and making breathing difficult. This results in chronic respiratory infections, often with Staphylococcus aureus or Pseudomonas aeruginosa. Chronic cough, recurrent pneumonia, and the progressive loss of lung function are the major manifestations of lung disease, which is the most common cause of death of persons with cystic fibrosis.

In the digestive system, the abnormally thick mucous secretions interfere with the passage of digestive enzymes and thus block the body's absorption of essential nutrients. The resulting maldigestion and malabsorption of food can cause affected individuals to become malnourished despite an adequate diet. Bulky, greasy, foul-smelling stools are often the first signs of cystic fibrosis. About 10 percent of infants with cystic fibrosis have intestinal obstruction at birth due to very thick secretions.

Cystic fibrosis causes the sweat glands to produce sweat that has an abnormally high salt content. The high salt content in perspiration is the basis for the "sweat test," which is the definitive diagnostic test for the presence of cystic fibrosis.

The treatment of cystic fibrosis includes the intake of pancreatic enzyme supplements and a diet high in calories, protein, and fat. Vigorous physical therapy on a daily basis is used to loosen and drain the mucous secretions that accumulate in the lungs. Antibiotics are regularly ingested in order to fight the accompanying lung infections; the enzyme deoxyribonuclease also is administered to clear mucus and reduce infection. Cystic fibrosis was not recognized as a separate disease until 1938 and was then classified as a childhood disease because mortality among afflicted infants and children was high; by the mid-1980s, however, more than half of all victims of cystic fibrosis survived into adulthood owing to the aggressive therapeutic measures described above. Adult males who have cystic fibrosis usually are sterile.