|
|
| DiseaseID |
HGD4 |
| Genetic
Disorder |
CYSTIC FIBROSIS
|
| Gene
Name |
Cystic Fibrosis Transmembrane Regulator (CFTR) gene |
| Description |
Cystic fibrosis (CF) is the most common, fatal genetic disease in the United States. About 30,000 people in the United States have the disease. CF causes the body to produce thick, sticky mucus that clogs the lungs, leads to infection, and blocks the pancreas, which stops digestive enzymes from reaching the intestine where they are required in order to digest food.
Cystic fibrosis affects epithelia of the respiratory tract, exocrine pancreas, intestine, male genital tract, hepatobiliary system, and exocrine sweat glands, resulting in complex multisystem disease. Pulmonary disease is the major cause of morbidity and mortality in CF. Affected individuals have lower airway inflammation and chronic endobronchial infection, progressing to end-stage lung disease characterized by extensive airway damage (bronchiectasis, cysts, and abscesses) and fibrosis of lung parenchyma. Meconium ileus occurs at birth in 15%-20% of newborns with CF. Pancreatic insufficiency with malabsorption occurs in the great majority of individuals with CF. More than 95% of males with CF are infertile as a result of azoospermia caused by absent, atrophic, or fibrotic Wolffian duct structures.
|
| Symptoms |
The specific signs and symptoms of cystic fibrosis can vary with the severity of the disease. For example, one child with cystic fibrosis may have respiratory problems but not digestive problems, while another child may have both. In addition, the signs and symptoms of cystic fibrosis may vary with age.
Signs and symptoms in newborns :
In some newborns, the first sign may be a blockage of their intestines (meconium ileus). This occurs when meconium — tarry, greenish-black stools normally passed by an infant during the first day or two after birth — becomes so thick it can't move through the intestines. Other signs in newborns may include:
? Failure to grow
? Bulky and greasy stools (steatorrhea)
? Frequent respiratory infections
Signs and symptoms in children and young adults:
Cystic fibrosis symptoms in children and young adults may include:
? Salty taste to the skin. People with cystic fibrosis tend to have higher than normal amounts of salt (sodium chloride) in their sweat. This may be one of the first signs parents notice because they can taste the salt when they kiss their child.
? Blockage in the bowels.
? Foul-smelling, greasy stools.
? Delayed growth.
? Thick sputum. It's easy for parents to overlook this sign because young children tend to swallow their sputum rather than cough it up.
? Coughing or wheezing.
? Frequent chest and sinus infections with recurring pneumonia or bronchitis.
? Protrusion of part of the rectum through the anus (rectal prolapse). This is often caused by stools that are difficult to pass or by frequent coughing.
? Enlargement or rounding (clubbing) of the fingertips and toes. Although clubbing eventually occurs in most people with cystic fibrosis, it also occurs in some people born with heart disease and other types of lung problems.
Cystic fibrosis may also be accompanied by:
? Growths (polyps) in the nasal passages
? Cirrhosis of the liver due to inflammation or obstruction of the bile ducts
? Displacement of one part of the intestine into another part of the intestine (intussusception) in children older than age 4
|
| Causes |
Cystic fibrosis (CF) is caused by a defective gene which tells the body to produce abnormally thick and sticky fluid, called mucus. This mucus builds up in the breathing passages of the lungs and the pancreas, the organ that helps to break down and absorb food.
This collection of sticky mucus results in life-threatening lung infections and serious digestion problems. The disease may also affect the sweat glands and a man's reproductive system.
Millions of Americans carry the defective CF gene, but do not have any symptoms. That's because a person with CF must inherit two defective CF genes -- one from each parent. An estimated 1 in 29 Caucasian Americans have the CF gene. The disease is the most common, deadly, inherited disorder affecting Caucasians in the United States. It's more common among those of Northern or Central European descent.
Most children are diagnosed with CF by their 2nd birthday. A small number, however, are not diagnosed until age 18 or older. These patients usually have a milder form of the disease |
| Diagnosis |
Most commonly the diagnosis of cystic fibrosis (CF) is established in individuals with one or more characteristic phenotypic features of CF plus evidence of an abnormality in cystic fibrosis transmembrane conductance regulator (CFTR) function based on one of the following: presence of two disease-causing mutations in the CFTR gene or two abnormal quantitative pilocarpine iontophoresis sweat chloride values (>60 mEq/L) or transepithelial nasal potential difference (NPD) measurements characteristic of CF. The CFTR mutation detection rate varies by test method and ethnic background. In some symptomatic individuals, only one or neither disease-causing mutation is detectable; in some carriers, the disease-causing mutation is not detectable.
|
| Treatment |
Many treatments exist for the symptoms and complications of cystic fibrosis. The main goal is to prevent infections, reduce the amount and thickness of secretions in the lungs, improve airflow, and maintain adequate calories and nutrition.
To accomplish these objectives, cystic fibrosis treatment may include:
? Antibiotics. Newer antibiotics may more effectively fight the bacteria that cause lung infections in people with cystic fibrosis. Among these are aerosolized antibiotics that send medication directly into airways. One of the major drawbacks of long-term use of antibiotics is the development of bacteria that are resistant to drug therapy. In addition, using antibiotics over a long period of time can lead to fungal infections of the mouth, throat and respiratory tract.
? Mucus-thinning drugs. When your white blood cells attack bacteria in your airways, DNA in your cells is released, making the mucus in your airways even thicker. The aerosolized drug dornase alfa (Pulmozyme) is an enzyme that fragments DNA, making mucus thinner and easier to cough up. Side effects of the drug may include airway irritation and sore throat.
? Bronchodilators. Use of medications such as albuterol, which can be delivered by an inhaler or a nebulizer, may help keep open the bronchial tubes by clearing thick secretions.
? Bronchial airway drainage. People with cystic fibrosis need a way to physically remove thick mucus from their lungs. This is often done by manually clapping with cupped hands on the front and back of the chest — a procedure that's best performed with the person's head over the edge of the bed so that gravity helps clear the secretions.
In some cases an electric chest clapper, known as a mechanical percussor, is used. An inflatable vest that vibrates at high frequency also can help people with cystic fibrosis cough up secretions. Many adults and children with pulmonary cystic fibrosis need to have bronchial airway drainage at least twice a day for 20 to 30 minutes. Older children and adults can learn to do this themselves, especially if they use mechanical aids, such as vests and percussors. Young children need the aid of parents, grandparents or older siblings.
? Oral enzymes and better nutrition. Cystic fibrosis can cause you to become malnourished because the pancreatic enzymes needed for digestion don't reach your small intestine, preventing food from being absorbed. As a result, you may need many more calories than you otherwise would. Supplemental high-calorie nutrition, special fat-soluble vitamins and enteric-coated oral pancreatic enzymes can help you maintain or even gain weight.
? Lung transplantation. Your doctor may suggest lung transplantation if you have severe breathing problems, life-threatening pulmonary complications or increasing resistance to antibiotics used to treat lung infections. Whether you're a good candidate for the procedure depends on a number of factors, including your overall health, certain lifestyle factors and the availability of donor organs. Because both lungs are affected by cystic fibrosis, both need to be replaced. If your chest isn't large enough to hold two adult donor lungs, your surgeon is likely to use two lower lobes contributed by two living donors. However it's performed, lung transplantation is a major operation and may lead to serious complications, especially post-surgical infections.
? Pain relievers. Ibuprofen (Advil, Motrin, others) may slow lung deterioration in some children with cystic fibrosis.
Future treatments
Major progress in cystic fibrosis research came in 1989, when researchers identified the genetic mutation that causes the disease. Since then scientists have been studying ways to insert copies of the normal gene into cells of the respiratory tract.
The challenge has been to find a reliable way to deliver the normal genetic material to affected cells that line the airways. Several methods have been developed as delivery systems, including using modified viruses, fat capsules (liposomes) and synthetic vectors. Clinical trials are under way to test the effectiveness of these delivery systems.
Other research is focusing on modifying the protein that the cystic fibrosis gene produces. This may help normalize the movement of salt and water in and out of the cells. |
|
|
