Cystic fibrosis (CF) is an autosomal recessive condition affecting approximately 30,000 Americans and 60,000 people worldwide. According to the Centers for Disease Control and Prevention (CDC), approximately 1,000 new cases are diagnosed yearly in the United States, with a known incidence of 1 per 3,900 live births. The disease prevalence varies greatly by ethnicity, with the highest prevalence occurring in Western European descendants and within the Ashkenazi Jewish population.
The cystic fibrosis gene, located on chromosome 7, was first identified in 1989. The disease process is caused by a mutation to the gene that encodes for the cystic fibrosis transmembrane conductance regulator (CFTR) protein. This mutation alters the production, structure, and function of cAMP (cyclic adenosine monophosphate), a dependent transmembrane chloride channel carrier protein found in the exocrine mucus glands throughout the body. The mutated carrier protein is unable to transport chloride across the cell membrane, resulting in an electrolyte and charge imbalance. Diffusion of water across the cell membrane is thus impaired, resulting in the development of a viscous layer of mucus. The thick mucus obstructs the cell membranes, traps nearby bacteria, and incites a local inflammatory response. Subsequent bacterial colonization occurs at an early age and ultimately this repetitive infectious process leads to progressive inflammatory damage to the organs involved in individuals with CF.
CF involves the exocrine mucous glands and typically affects the lungs, liver, pancreas, gastrointestinal tract, sweat glands, and genitourinary tracts. The severity of the disease and the organs affected depends largely on the specific type of genetic mutation involved. To date there are more than 1,200 known mutations of the CFTR gene, not all of which cause CF.
The specific type of mutation dictates the organ systems involved, the pathology observed, and the disease severity. The most prevalent mutation to the CFTR gene is the Delta-F508 mutation, accounting for 66% of CF patients worldwide. The Delta-F508 mutation is a deletion of only three nucleotide base pairs in the CFTR gene, resulting in the absence of the amino acid phenylalanine in the protein. Patients with the Delta-F508 mutation have predominant impairments in body structure and function of both the respiratory and gastrointestinal tracts. The respiratory system impairments in CF may include airway obstruction with recurrent and progressive lung infections (such as recurrent pneumonia), chronic bronchitis, asthma, chronic cough, and nasal polyps. Gastrointestinal system impairments may include pancreatic enzyme insufficiency, fat and protein malabsorption, type 1 or 2 diabetes mellitus, failure to thrive, abdominal pain, increased flatulence, intestinal obstruction, cirrhosis, pancreatic inflammation, and bulky, greasy, foul-smelling stools. In addition, the genitourinary systems in males with CF is impaired, with a 97% infertility rate due to congenital absence of the vas deferens, with a smaller percentage of men having obstructive azoospermia. The incidence of infertility of females with CF is not well documented but appears to be much less then in males. Female infertility in CF is primarily due to ...