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Cystic Fibrosis

Cystic Fibrosis

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FACTS ABOUT

Cystic

What Is What Are the Cystic fibrosis (CF) is a chronic, progressive, of CF? and frequently fatal genetic (inherited) dis­ CF does not follow the same pattern in all ease of the body’s glands. CF pri­ patients but affects different people in dif­ marily affects the respiratory and digestive ferent ways and to varying degrees. systems in children and young adults. The However, the basic problem is the same— sweat glands and the reproductive system an abnormality in the glands, which pro­ are also usually involved. On the average, duce or secrete sweat and mucus. Sweat individuals with CF have a lifespan of cools the body; mucus lubricates the respi­ approximately 30 years. ratory, digestive, and reproductive systems, and prevents tissues from drying out, pro­ CF-like disease has been known for over tecting them from . two centuries. The name, cystic fibrosis of the , was first applied to the disease People with CF lose excessive amounts of in 1938. salt when they sweat. This can upset the balance of minerals in the blood, which may How Common Is CF? cause abnormal heart rhythms. Going into shock is also a risk. According to the data collected by the Cystic Fibrosis Foundation, there are about Mucus in CF patients is very thick and 30,000 Americans, 3,000 Canadians, and accumulates in the intestines and . 20,000 Europeans with CF. The disease The result is , poor growth, occurs mostly in whites whose ancestors frequent respiratory , breathing came from northern Europe, although it difficulties, and eventually permanent affects all races and ethnic groups. damage. Lung disease is the usual cause of Accordingly, it is less common in African death in most patients. Americans, Native Americans, and Asian CF can cause various other medical prob­ Americans. Approximately 2,500 babies are lems. These include ( born with CF each year in the United of the nasal sinuses, which are cavities in States. Also, about 1 in every 20 the skull behind, above, and on both sides Americans is an unaffected carrier of an of the nose), nasal polyps (fleshy growths abnormal “CF .” These 12 million inside the nose), clubbing (rounding and people are usually unaware that they are enlargement of fingers and toes), pneu­ carriers. mothorax (rupture of lung tissue and trap-

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ping of air between the lung and the

chest wall), (coughing of CYSTIC FIBROSIS GENE blood), cor pulmonale (enlargement of the right side of the heart), AUTOSOMAL RECESSIVE INHERITANCE abdominal pain and discomfort, gassiness (too much gas in the intes­ Carrier Father Carrier Mother tine), and (protrusion of the through the anus). disease, , 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

usually has symptoms during Gg Gg 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 GG Gg Gg gg , bulky foul-smelling and greasy stools, frequent wheezing or , a chronic with thick mucus, salty-tasting , or poor growth. CF should be suspect­ ed in babies born with an intestinal blockage called ileus.

How Is CF Diagnosed? Normal Carrier Carrier Affected The most common test for CF is called the sweat test. It measures the

amount of salt (sodium chloride) in The presence of two mutant genes (g) is needed for CF to appear. Each parent the sweat. In this test, an area of the carries one defective gene (g) and one normal gene (G). The single normal skin (usually the forearm) is made to gene is sufficient for normal function of the mucus glands, and the parents are sweat by using a chemical called therefore CF-free. Each child has a 25 percent risk of inheriting two defective and applying a mild elec­ genes and getting CF, a 25 percent chance of inheriting two normal genes, tric current. To collect the sweat, the and a 50 percent chance of being an unaffected carrier like the parents. 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

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chloride suggest that the person has can cause the body to make a defec­ for the basic causes of CF, although cystic fibrosis. tive protein or no protein at all. The several drug-based approaches are result is a loss of some essential bio­ being investigated. In the mean­ The sweat test may not work well in logical function and that leads to time, the best that doctors can do is newborns because they do not pro­ disease. Children may inherit altered to ease the symptoms of CF or slow duce enough sweat. In that case, genes from one or both parents. the progress of the disease so the another type of test, such as the patient’s quality of life is improved. immunoreactive test Diseases such as CF that are caused This is achieved by thera­ (IRT), may be used. In the IRT test, by inherited genes are called genetic py combined with treatments to blood drawn 2 to 3 days after birth diseases. In CF, each parent carries clear the thick mucus from the is analyzed for a specific protein one abnormal CF gene and one nor­ lungs. The therapy is tailored to the called trypsinogen. Positive IRT mal CF gene but shows no evidence needs of each patient. For patients tests must be confirmed by sweat of the disease because the normal CF whose disease is very advanced, lung and other tests. gene dominates or “recesses” the transplantation may be an option. abnormal CF gene. To have CF, a Also, a small percentage of people child must inherit two abnormal CF was once always fatal in child­ with CF have normal sweat chloride genes—one from each parent. The hood. Better treatment methods levels. They can only be diagnosed recessive CF gene can occur in both developed over the past 20 years by chemical tests for the presence of boys and girls because it is located have increased the average lifespan the mutated gene. Some of the on non-sex-linked chromosomes of CF patients to nearly 30 years. other tests that can assist in the called autosomal chromosomes. CF These treatment approaches are diagnosis of CF are chest x-rays, is therefore called an autosomal detailed more fully below: lung function tests, and recessive genetic disease. () cultures. Stool examina­ ■ Management of lung problems tions can help identify the digestive The inheritance patterns for the CF A major focus of CF treatment is the abnormalities that are typical of CF. gene are shown in the accompany­ obstructed breathing that causes ing diagram. Each child, whether frequent lung infections. Physical What Makes CF a Genetic male or female, has a 25 percent risk therapy, exercise, and medications Disease? of inheriting a defective gene from are used to reduce the mucus block­ each parent and of having CF. A Genes are the basic units of heredity. age of the lung’s airways. child born to two CF patients (an They are located on structures with­ unlikely event) would be at a 100 Chest therapy consists of bronchial, in the cell nucleus called chromo­ percent risk of developing CF. or postural, drainage, which is done somes. The function of most genes by placing the patient in a position is to instruct the cells to make par­ that allows drainage of the mucus ticular proteins, most of which have How Is CF Treated? from the lungs. At the same time, important life-sustaining roles. Since CF is a genetic disease, the the chest or back is clapped (per­ only way to prevent or cure it would Every human being has 46 chromo­ cussed) and vibrated to dislodge the be with at an early somes, 23 inherited from each par­ mucus and help it move out of the age. Ideally, gene therapy could ent. Because each of the 23 pairs of airways. This process is repeated repair or replace the defective gene. chromosomes contains a complete over different parts of the chest and Another option for treatment would set of genes, every individual has back to loosen the mucus in differ­ be to give a person with CF the two sets (one from each parent) of ent areas of each lung. This proce­ active form of the protein product genes for each function. In some dure has to be done for children by that is scarce or missing. individuals, the basic building family members but older patients blocks of a gene (called base pairs) At present, neither gene therapy nor can learn to do it by themselves. are altered (mutated). A any other kind of treatment exists Mechanical aids that help chest

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are available com­ treat the gene abnormality that mercially. Exercise also helps to causes CF. In the laboratory, scien­ loosen the mucus, stimulate cough­ tists have been able to grow cells HOW DOES THE GENE MUTATION ing to clear the mucus, and improve from the nasal passages of CF CAUSE CF? the patient’s overall physical patients. By introducing the normal condition. gene into these cells, researchers corrected the cells’ chloride trans­ The CF gene was identified in 1989. Medications used to help breathing abnormality. The chloride Since then, a great deal has been learned are often aerosolized (misted) and defect has also been corrected in about this gene and its protein product. can be inhaled. These medicines small regions in the nasal passages The biochemical abnormality in CF include bronchodilators (which themselves by giving CF patients results from a mutation in a gene that widen the breathing tubes), the normal gene in nose drops. produces a protein responsible for the mucolytics (which thin the mucus), movement through the cell membranes and decongestants (which reduce Scientists are still looking for of chloride (a component of sodium swelling of the membranes of the answers to many questions about chloride, or common table salt). The breathing tubes). A recent advance, gene therapy. Some of these ques­ protein is called CFTR—cystic fibrosis approved by the Food and Drug tions are: How should the gene be transmembrane regulator. Administration, is an inhaled packaged? What are the best ways aerosolized enzyme that thins the to get the gene-containing package CFTR is present in cells that line the mucus by digesting the cellular into the patient’s lungs? What will passageways of the lungs, pancreas, material trapped in it. to the long-term results of this treat­ colon, and genitourinary tract. When fight lung infections also are used ment be? Can the abnormal chloride this protein is abnormal, two of the and may be taken orally or in transport be corrected in other parts hallmarks of CF result—blockage of the aerosol form, or by injection into a of the body? How long will the cor­ movement of chloride ions and water in vein. rection last? And, most importantly, the lung and other cells and secretion of can gene therapy cure or prevent abnormal mucus. ■ Management of digestive the lung disease in CF? problems The mutation involved in CF causes the of three of the base pairs in the The digestive problems in CF are Is It Possible to Detect CF in gene. This in turn, causes a loss in the less serious and more easily man­ an Unborn Baby? CFTR protein of an (the aged than those in the lungs. A Finding out whether a baby is likely building blocks of proteins). Because well-balanced, high-caloric diet, to have CF is possible using prenatal is located in position 508 low in fat and high in protein, and genetic tests. However, the tests of the protein chain, this mutant protein pancreatic enzymes (which help cannot detect all of the CF gene is called DF508 CFTR. ) are often prescribed. . Also, because these tests D Supplements of A, D, E, However, F508 CFTR accounts for only are very expensive and have certain and K are given to ensure good 70-80 percent of all CF cases. Various risks to the mother, they are not nutrition. Enemas and mucolytic other mutations—over 400 at the last used for all pregnant women. If agents are used to treat intestinal count—seem to be responsible for the there is another child with CF in the obstructions. remaining CF cases. Differences in family, the expectant mother may disease patterns seen in individuals and request a prenatal test to see if the Gene Therapy—The Future of families probably result from the fetus has CF genes from both par­ CF Treatment? combined effects of the particular ents, is a carrier for one gene, or is mutation and various, but still unknown, Gene therapy for CF is not yet pos­ altogether free of the CF genes. factors in the CF patient and his or her sible but impressive progress is There are two special prenatal tests environment. being made in developing ways to

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that can be done—either an amnio­ How Can Patients and Their although they may be less fertile centesis or chorionic villus biopsy Families and Friends Be than women without CF. will be performed. In , Helped To Cope with CF? ■ Patients and families should cells from the fluid surrounding the CF education helps patients and work closely with doctors and other baby in the mother’s womb (called their families face the physical and medical specialists to develop self- the amniotic fluid) are tested to see emotional effects of the disease and management skills that can improve if the CF genes common to the par­ encourages CF patients to lead their quality of life. ents are present. In chorionic villus active, fulfilling lives. Educational Above all, CF patients and their biopsy, cells from the tissue that will programs and materials suitable for families should keep a positive atti­ eventually form the placenta are both patients of various ages and tude. Scientists continue to make tested for the CF gene. their parents are available from local significant advances in understand­ CF centers and from local chapters ing the genetic and physiological Can CF Be Prevented? of the CF Foundation. disturbances in CF and in develop­ At this time, preventing CF is not Patients and their families and ing new treatment approaches such possible. In babies with two abnor­ friends should know that: as gene therapy. The outlook is mal CF genes, the disease is already bright for further improvements in present at birth in some organs, ■ CF parents should not feel guilty the care of CF patients and even for such as the pancreas and liver, but or responsible for causing their the discovery of a cure. develops only after birth in the child’s disease; they could not have lungs. Someday, gene therapy may prevented it. be used to prevent the lung disease ■ Parents should treat their chil­ from developing. dren with CF as normally as possi­ Yet, CF might be prevented in the ble. They shouldn’t be over-pro­ future. Since CF occurs only when tective but should encourage them both parents pass on a CF gene to a to be active and self-reliant. child, it could be prevented by iden­ ■ Family and friends should tifying all carriers of CF genes. remember that CF is not conta­ Genetic counselors might then per­ gious; nobody can get it from a suade couples who are carriers not patient. to have children. However, as noted, current tests can detect only some of ■ In families with CF, brothers, sis­ the more than 400 gene mutations ters, and first cousins of the CF and so the tests are only 80-85 per­ patient should be tested to see if cent accurate. they carry a defective gene, especial­ ly if they seem to have a chronic Yet, progress in gene therapy and lung or digestive problem. Carriers the realization that not all CF muta­ of the abnormal gene should get tions are life-threatening should . reassure couples. Potential parents who carry the defective gene may ■ Individuals with CF have normal choose to have children. sexual development and can expect to have a normal sex life. However, most, but not all, men are infertile because of a mechanical blockage of sperm and cannot have children. Women with CF can have children,

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FOR MORE INFORMATION

Additional information about CF can be obtained from the following organizations:

National Heart, Lung, and Blood Institute (NHLBI) Information Center P.O. Box 30105 Bethesda, MD 20824-0105 Telephone: 301-251-1222

The Cystic Fibrosis Foundation 6931 Arlington Road, #200 Bethesda, MD 20814 Telephone: 301-951-4422 1- 800-344-4823

National Diabetes Information Clearinghouse 1 Information Way Bethesda, MD 20892-3560 Telephone: 301-654-3327 1-800-891-5388

U.S. DEPARTMENT OF HEALTH AND HUMAN SERVICES

Public Health Service National Institutes of Health National Heart, Lung, and Blood Institute

NIH Publication No. 95-3650

6 November 1995

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