Genetic Diseases - Cystic Fibrosis

CF is the most common inherited fatal disease among children and young adults in the United States. It occurs most commonly in white people (in one of every 3,200 births of white children and in one in 3,900 of all Americans), and there are approximately 30,000 young people who have the disease; their median (half above and half below) life span is 33.4 years. However, as more medical advances are made in treating CF, the number of adults with CF is growing; in fact, in 2003 almost 40 percent of those with CF are age eighteen and older. Unfortunately, additional health problems—such as CF-related diabetes and osteoporosis and reproductive problems (95 percent of men with CF are infertile)—occur in adults with CF.

More than ten million Americans, almost all of whom are white, are symptomless carriers of the CF gene. To inherit this disease, a child must receive the CF gene from both parents.

At first, a child with CF does not appear to have a serious illness, but the diagnosis usually is made by the age of three years. Often, the only signs are a persistent cough; a large appetite but poor weight gain; an extremely salty taste to the skin; and large, foul-smelling bowel movements. A simple "sweat test" is currently the standard diagnostic test for CF. The test measures the amount of salt in the sweat; abnormally high levels are the hallmark of CF.

Children with CF have great difficulty breathing. The CF gene causes the body to produce thick, sticky mucus in the lungs and pancreas, causing difficulty in breathing and interference with digestion. This thick drainage must be removed constantly.

Cystic Fibrosis Gene-Screening Falters

In August 1989 researchers isolated the specific gene that causes CF. The mutation of this gene accounts for about 70 percent of the cases of the disease. In 1990 scientists successfully corrected the biochemical defect by inserting a healthy gene into diseased cells grown in the laboratory, a major step toward developing new therapies for the disease. In 1992 they injected healthy genes into laboratory rats by using a deactivated common cold virus as the delivery agent. The rats began to manufacture the missing protein, which regulates the chloride and sodium in the tissues, preventing the deadly buildup of mucus. Scientists were hopeful that within only a few years CF would be eliminated as a fatal disease, giving many children the chance for healthy, normal lives.

In 1993, however, optimism faded when the medical community discovered that the CF gene was more complicated than expected four years earlier. Biologists found that the gene can be mutated at hundreds of points, and more points are being discovered at an alarming rate. At the same time, they discovered that many people who have inherited mutated genes from both parents do not have CF. With so many possible mutations, the potential combinations in a person who inherits one gene from each parent are immeasurable.

The combinations of different mutations create different effects. Some may result in crippling and fatal CF, whereas others may cause less serious disorders, such as infertility, asthma, or chronic bronchitis. To further complicate the picture, other genes can alter the way different mutations of the CF gene affect the body.

Researchers also are finding that CF mutations may be much more common than previously thought. Five thousand healthy women receiving prenatal care at Kaiser Permanente in northern California were tested for the CF gene, thought to be present in less than 1 percent of the population. Of those screened, 11 percent had the mutation. This may show that many more common diseases, such as asthma, may be caused by mutations of the CF gene.

In 2002, results from the Phase III clinical trial of the antibiotic azithromycin supported by the Cystic Fibrosis Foundation were very encouraging. Results showed that patients with CF who took the antibiotic experienced an almost 50 percent reduction in hospitalizations, had a significant improvement in lung function, and gained weight.

Currently, more than two dozen potential CF therapies are in the drug development pipeline. Any one of these—or a combination—could have a profound affect on the lives and future of people with CF, according to the Cystic Fibrosis Foundation.

Cystic Fibrosis Carrier Screening

Since the discovery in 1989 of the gene (called CFTR) that causes CF, more than 900 mutations of the gene have been identified. Screening is available for the most frequent CF mutations.

In 2000 the National Institutes of Health (NIH), American College of Medical Genetics, and American College of Obstetricians and Gynecologists (ACOG) issued a recommendation that CF screening be recommended to every white woman who is pregnant or considering having a baby. The same year the results of a research study conducted at Northwestern University Medical School in Chicago found that many people who carry the CF gene fail to inform family members about their risk.

However, further research ushered another change by ACOG in 2001. As a result of discoveries made by the human genome project, the organization issued the recommendation that obstetrician–gynecologists make DNA screening for cystic fibrosis available to all couples seeking preconception or prenatal care—not just to those with a personal or family history of carrying the CF gene, as recommended in 2000.