Cystic Fibrosis: Symptoms, Diagnosis, and Treatment

Introduction to Cystic Fibrosis

There are a number of fatal diseases with which a person can be born. One of the most debilitating is cystic fibrosis. It is important to examine its history, symptoms, diagnostic procedures, treatments, and prognosis in order to gain a better understanding of this disease.

Cystic fibrosis is a "recessive disorder common among Caucasians. Although the disease was known in the 1930s, it was only in the late 1980s that the molecular mechanisms of its development were established" (Tsui). In the United States, one in 2,500 people in the general population is born with cystic fibrosis.

Cystic fibrosis is sometimes referred to as "65 roses." This nickname came from a little boy who overheard his mother talking about the condition on the phone. He thought that each time she said "cystic fibrosis," she was talking about 65 roses.

Occurrence and Genetic Mutations

In the United States, the distribution of cystic fibrosis mutations among Caucasians is as follows:

50% have two copies of ΔF508 (the most common mutation); 40% have one copy of the deletion and one other mutation; and 10% do not have the ΔF508 deletion. In cystic fibrosis carriers of other ethnic backgrounds, the ΔF508 deletion is present in 45% of Italians, 30% of African Americans, and 30% of Ashkenazi Jews.

Cystic fibrosis presents with a number of symptoms. These can include: no meconium stool in the first 24 hours of life; pale, clay-colored, and foul-smelling stools; floating stools; salty-tasting skin in infants; persistent respiratory infections such as pneumonia; coughing or wheezing; weight loss; clubbing of the fingers or toes; diarrhea; delayed growth; easy fatigue; and splenomegaly.

Symptoms and Their Causes

Meconium is a black, tarry stool-like substance that passes shortly after birth, within the first few days of life. When a baby is unable to expel this meconium due to a blockage in the bowel, the condition is referred to as Meconium Ileus. In a baby with cystic fibrosis, the meconium may not be expelled due to intestinal secretions causing a blockage. Meconium Ileus occurs in approximately 15% of cases, is a very serious condition, and requires surgery within a few hours; otherwise, the baby will not survive.

Patients with cystic fibrosis may not be able to digest food correctly due to pancreatic insufficiency, resulting in the production of greasy, bulky, foul-smelling stools.

Cystic fibrosis may cause a condition known as "Failure to Thrive," during which a child is unable to gain weight or grow in height normally.

Patients with cystic fibrosis may experience recurring lung and sinus infections and carry a large volume of secretions in the respiratory system. These secretions are difficult to clear because they are thick and often infected. These chronic respiratory infections may cause frequent coughing, and patients who also suffer from asthma may experience wheezing.

Sufferers may have nasal congestion from chronic sinusitis and/or polyps, with nasal polyps sometimes requiring surgery. Patients may be infected with Pseudomonas aeruginosa or Burkholderia cepacia. Foul-smelling breath, which no amount of brushing or breath fresheners can eliminate, may be present — usually due to respiratory infections such as Pseudomonas aeruginosa — but may also result from improper digestion.

The most basic symptom of cystic fibrosis is salty sweat. The patient may also dehydrate easily, find it difficult to gain weight due to malabsorption and the energy demands of fighting infection, experience stomach aches, and have vitamin or mineral deficiencies due to malabsorption, especially Vitamin K.

In the decade preceding publication of these sources, there were a number of advances in the diagnosis of cystic fibrosis owing to research in molecular biology and genetics. Early diagnosis of the disease can lead to the most appropriate medical management of the patient and allows for genetic counseling and pulmonary surveillance (Andolsek).

The traditional diagnostic criteria for cystic fibrosis include persistently elevated concentrations of electrolytes in sweat, along with characteristic clinical findings — such as typical gastrointestinal or pulmonary disease and perhaps obstructive azoospermia — or a family history (Andolsek). Sweat testing is the main diagnostic tool used to determine classic cystic fibrosis; however, additional tests must be used to identify atypical forms of the disease.

There may be complications in diagnosing patients with an atypical form of the disease, including patients who present with cystic fibrosis late in childhood or in adulthood. These patients may lack characteristic gastrointestinal and pulmonary symptoms and may present with less widely recognized complications such as pancreatitis, congenital absence of the vas deferens, and nasal polyps (Andolsek).

Health care practitioners may administer a number of additional tests to confirm cystic fibrosis. These can include sweat testing, genotyping, semen analysis, sinus radiographs, tests of exocrine pancreatic function, nasal potential-difference measurements, and bronchoalveolar lavage. The correlation of genotype with phenotype, as well as the rational use of clinical signs and laboratory tests, is used to both diagnose and rule out cystic fibrosis (Andolsek).

Diagnosis of Cystic Fibrosis

The encoded gene product known as the cystic fibrosis transmembrane conductance regulator (CFTR) has been identified through gene mapping and cloning techniques. Studies have shown, however, that CFTR mutations extend beyond cystic fibrosis alone by inducing pancreatic disorder (Tsui).

In conditions involving single-gene disorders such as cystic fibrosis, the chromosomes — or karyotype — are expected to be normal (46, XX or 46, XY); therefore, chromosome studies are not recommended for these patients.

Cystic fibrosis is a hereditary disease. To inherit it, two abnormal genes — one from each parent — must be passed on. Genetic testing can show whether a person carries the common gene changes known to cause cystic fibrosis by analyzing DNA from a small number of cells or a blood sample. The easiest methods of collecting cells for genetic testing are using a cheek-brush kit to obtain cells from the mouth or drawing a blood sample. The DNA from these cells can be isolated and used in the laboratory to test for the presence of cystic fibrosis gene mutations.

While it is important for anyone who has a family history of cystic fibrosis to be tested as a carrier, 80% of children with cystic fibrosis are born to parents with no prior history of the disease. Testing can detect approximately 80–90% of cystic fibrosis carriers. While testing may not provide complete carrier-status information for all individuals, if a person is found to carry a mutation, then he or she is a carrier; if no identifiable mutation is found, the chance of being a carrier is much lower, but not zero.

In patients who do have a family history of cystic fibrosis, it is best to test the person with the disease first and determine which mutations he or she carries. Relatives can then be tested to see whether they carry the same mutations. If a close relative does not have these same mutations, the chance that they are a carrier is quite small.

Each gene has its own specific DNA code, which defines the gene's function. DNA is composed of four building blocks called bases. These bases are joined in a specific order for each gene, and when a change occurs in the arrangement of the bases, it can cause the gene to not work properly. A structural gene change that can cause a disease or a birth defect is called a mutation. As noted above, a person with cystic fibrosis inherits a mutated cystic fibrosis gene from each parent. This mutated gene is large, and there are currently over 700 known cystic fibrosis mutations, most of which are very rare. The most common mutation is referred to as the ΔF508 deletion. The form of genetic testing used to identify this deletion is known as direct testing, which can be performed on a single individual, thus eliminating the need to test the entire family at the same time.