Cystic fibrosis 30/7/03. By Richard Twyman Cystic fibrosis is a relatively common inherited disorder involving the accumulation of thick mucus in the lungs and pancreatic ducts.

This causes breathing difficulties, chronic respiratory infections and problems with digestion. Although there is no cure for the disease, appropriate clinical management in the form of physiotherapy, antibiotic treatment and a supplemented diet allows most patients to live well into their 30s.

Genetics

Cystic fibrosis is a single gene disorder caused by a malfunctioning gene on chromosome 7. It is a recessive disease , which means that both copies of the gene must be defective. It has the highest incidence of any recessive disease in Caucasian populations (approximately 1 in 2000) but it is less common in other population groups (1 in 15 000 in Africans, and 1 in 30 000 in Asians).

The disease gene is named CFTR, which stands for cystic fibrosis transmembrane conductance regulator. The normal product of this gene is a chloride channel, a protein whose function is to export chloride ions from the cell. The CFTR protein also helps to regulate the import of sodium ions. Its overall effect is to prevent the accumulation of salt (sodium chloride) inside mucus-producing cells, which is necessary to produce mucus of the correct consistency.

See the CFTR gene in the interactive chromosome browser [requires Flash]

Mutations that reduce the amount of CFTR protein or interfere with its activity allow salt to accumulate inside these cells, resulting in the production of thick, sticky mucus that does not drain away effectively.

Symptoms

The most common symptoms of cystic fibrosis are coughing and chronic breathing difficulties brought about by the excess mucus lining the lungs and respiratory tubes. This encourages persistent and repeated lung infections, often involving the bacterium Pseudomonas aeruginosa which rarely infects healthy people. Over time, the recurrent infections result in lung damage characterised by the deposition of fibrous cysts, hence the name of the disease. The infections and the damage they inflict become more difficult to manage over time, contributing to the early death of cystic fibrosis patients.

About 85 per cent of cystic fibrosis cases also include a pancreatic deficiency caused by mucus blocking the pancreatic ducts. The pancreas produces enzymes that are necessary to digest food, and in cystic fibrosis these enzymes are prevented from reaching the alimentary canal. Children with the disease suffer malnutrition, and gain weight very slowly.

Almost all males with cystic fibrosis are sterile because the vasa deferentia (the tubes that carry sperm) are missing. Some males have a very mild form of cystic fibrosis where sterility is the only symptom.

Diagnosis

Tests for cystic fibrosis are often carried out in children with persistent lung infections or growth problems. The disease is diagnosed using a simple test that measures the amount of salt in the sweat. Individuals with the disease have more salt in their sweat than unaffected people. If there is a family history of the disease, a prenatal test may be offered, which is based on the detection of mutations in the CFTR gene.

Treatment

The respiratory problems associated with cystic fibrosis can be reduced by daily therapy involving a parent of carer drumming on the back and chest of the patient to loosen the mucus and help clear it from the lungs. A mucus-thinning drug can also be used if necessary. These precautions reduce the risk of lung infections but do not eliminate them. Careful monitoring is required and the use of antibiotics such as tobramycin, often inhaled as a vapour, can be used to manage infections quite efficiently.

The pancreatic deficiency can be treated by supplementing the diet with pancreatic enzymes. Children with the disease often adhere to high-calorie diets supplemented with vitamins and minerals to ensure proper growth and development. Although there is no cure for the disease, there have been several attempts to provide medium to long-term relief using gene therapy .