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What Is Cystic Fibrosis ?>

Cystic fibrosis (CF) is a chronic, progressive, and frequently fatal genetic (inherited) disease of the body's mucus glands. CF primarily affects the respiratory and digestive systems in children and young adults. The sweat glands and the reproductive system are also usually involved.

On the average, individuals with CF have a lifespan of approximately 30 years. CF-like disease has been known for over two centuries. The name, cystic fibrosis of the pancreas, was first applied to the disease in 1938.

How Common Is CF?

According to the data collected by the Cystic Fibrosis Foundation, there are about 30,000 Americans, 3,000 Canadians, and 20,000 Europeans with CF.

The disease occurs mostly in whites whose ancestors came from northern Europe, although it affects all races and ethnic groups. Accordingly, it is less common in African Americans, Native Americans, and Asian Americans. Approximately 2,500 babies are born with CF each year in the United States. Also, about 1 in every 20 Americans is an unaffected carrier of an abnormal "CF gene." These 12 million people are usually unaware that they are carriers.

What Are the Signs and Symptoms of CF? CF does not follow the same pattern in all patients but affects different people in different ways and to varying degrees. However, the basic problem is the same-an abnormality in the glands, which produce or secrete sweat and mucus. Sweat cools the body; mucus lubricates the respiratory, digestive, and reproductive systems, and prevents tissues from drying out, protecting them from infection.

People with CF lose excessive amounts of salt when they sweat. This can upset the balance of minerals in the blood, which may cause abnormal heart rhythms. Going into shock is also a risk. Mucus in CF patients is very thick and accumulates in the intestines and lungs. The result is malnutrition, poor growth, frequent respiratory infections, breathing difficulties, and eventually permanent lung damage.

Lung disease is the usual cause of death in most patients.

CF can cause various other medical problems. These include sinusitis (inflammation of the nasal sinuses, which are cavities in the skull behind, above, and on both sides of the nose), nasal polyps (fleshy growths inside the nose), clubbing (rounding and enlargement of fingers and toes), pneumothorax (rupture of lung tissue and trapping of air between the lung and the chest wall), hemoptysis (coughing of blood), cor pulmonale (enlargement of the right side of the heart), abdominal pain and discomfort, gassiness (too much gas in the intestine), and rectal prolapse (protrusion of the rectum through the anus). Liver disease, diabetes, inflammation of the pancreas, and gallstones also occur in some people with CF.

When Should You Suspect That a Child May Have CF?

CF symptoms vary from child to child. A baby born with the CF genes usually has symptoms during its first year. Sometimes, however, signs of the disease may not show up until adolescence or even later. Infants or young children should be tested for CF if they have persistent diarrhea, bulky foul-smelling and greasy stools, frequent wheezing or pneumonia, a chronic cough with thick mucus, salty-tasting skin, or poor growth. CF should be suspected in babies born with an intestinal blockage called meconium ileus.

How Is CF Diagnosed?

The most common test for CF is called the sweat test. It measures the amount of salt (sodium chloride) in the sweat. In this test, an area of the skin (usually the forearm) is made to sweat by using a chemical called pilocarpine and applying a mild electric current. To collect the sweat, the area is covered with a gauze pad or filter paper and wrapped in plastic. After 30 to 40 minutes, the plastic is removed, and the sweat collected in the pad or paper is analyzed. Higher than normal amounts of sodium and chloride suggest that the person has cystic fibrosis.

CYSTIC FIBROSIS GENE

The presence of two mutant genes (g) is needed for CF to appear. Each parent carries one defective gene (g) and one normal gene (G). The single normal gene is sufficient for normal function of the mucus glands, and the parents are therefore CF-free. Each child has a 25 percent risk of inheriting two defective genes and getting CF, a 25 percent chance of inheriting two normal genes, and a 50 percent chance of being an unaffected carrier like the parents.

The sweat test may not work well in newborns because they do not produce enough sweat. In that case, another type of test, such as the immunoreactive trypsinogen test (IRT), may be used. In the IRT test, blood drawn 2 to 3 days after birth is analyzed for a specific protein called trypsinogen. Positive IRT tests must be confirmed by sweat and other tests.

Also, a small percentage of people with CF have normal sweat chloride levels. They can only be diagnosed by chemical tests for the presence of the mutated gene. Some of the other tests that can assist in the diagnosis of CF are chest x-rays, lung function tests, and sputum (phlegm) cultures. Stool examinations can help identify the digestive abnormalities that are typical of CF.

What Makes CF a Genetic Disease?

Genes are the basic units of heredity. They are located on structures within the cell nucleus called chromosomes. The function of most genes is to instruct the cells to make particular proteins, most of which have important life-sustaining roles. Every human being has 46 chromosomes, 23 inherited from each parent. Because each of the 23 pairs of chromosomes contains a complete set of genes, every individual has two sets (one from each parent) of genes for each function. In some individuals, the basic building blocks of a gene (called base pairs) are altered (mutated). A mutation can cause the body to make a defective protein or no protein at all. The result is a loss of some essential biological function and that leads to disease. Children may inherit altered genes from one or both parents. Diseases such as CF that are caused by inherited genes are called genetic diseases. In CF, each parent carries one abnormal CF gene and one normal CF gene but shows no evidence of the disease because the normal CF gene dominates or "recesses" the abnormal CF gene. To have CF, a child must inherit two abnormal genes-one from each parent. The recessive CF gene can occur in both boys and girls because it is located on non-sex-linked chromosomes called autosomal chromosomes. CF is therefore called an autosomal recessive genetic disease. The inheritance patterns for the CF gene are shown in the accompanying diagram. Each child, whether male or female, has a 25 percent risk of inheriting a defective gene from each parent and of having CF. A child born to two CF patients (an unlikely event) would be at a 100 percent risk of developing CF.

How Does the Gene Mutation Cause CF?

The CF gene was identified in 1989. Since then, a great deal has been learned about this gene and its protein product. The biochemical abnormality in CF results from a mutation in a gene that produces a protein responsible for the movement through the cell membranes of chloride ions (a component of sodium chloride, or common table salt). The protein is called CFTR-cystic fibrosis transmembrane regulator. CFTR is present in cells that line the passageways of the lungs, pancreas, colon, and genitourinary tract. When this protein is abnormal, two of the hallmarks of CF result- blockage of the movement of chloride ions and water in the lung and other cells and secretion of abnormal mucus. The mutation involved in CF causes the deletion of three of the base pairs in the gene. This in turn, causes a loss in the CFTR protein of an amino acid (the building blocks of proteins). Because phenylalanine is located in position 508 of the protein chain, this mutant protein is called deltaF508 CFTR. However, deltaF508 CFTR accounts for only 70-80 percent of all CF cases. Various other mutations-over 400 at the last count-seem to be responsible for the remaining CF cases. Differences in disease patterns seen in individuals and families probably result from the combined effects of the particular mutation and various, but still unknown, factors in the CF patient and his or her environment.