This autosomal recessive exocrinopathy is one of the most common fatal genetic disorders in whites. Cystic ibrosis is caused by one of more than 2000 mutations in a 230-kb gene on the long arm of chromosome 7 that encodes an amino acid polypeptide (Patel, 2015; Sorscher, 2015). his peptide functions as a chloride channel and is termed the cystic ibrosis transmembrane conductance regulator (CFTR). As discussed in Chapter 14 (p. 289), phenotypes vary widely, even among homozygotes for the common 6F508 mutation (Rowntree, 2003). Approximately 10 to 20 percent of afected newborns are diagnosed shortly after birth because of meconium peritonitis (Boczar, 2015; Sorscher, 2015). Currently, the median predicted survival is 37 years, and nearly 80 percent of females with cystic ibrosis now survive to adulthood (Gillet, 2002; Patel, 2015).
Mutations in the chloride channel cause altered epithelial cell membrane transport of electrolytes. his afects all sites in which epithelium expresses CFTR-secretory cells. These include the sinuses, lung, pancreas, liver, and reproductive tract. Disease severity depends on which two alleles are inherited, and approximately 10 percent are disease-causing mutations (Sorscher, 2015). Homozygosity for Phe508del (�F508) is one of the most severe, and 90 percent of individuals with clinical disease carry at least one F508 allele.
Exocrine gland ductal obstruction develops from thick, viscid secretions (Rowe, 2005). In the lung, submucosal glandular ducts are afected. Eccrine sweat gland abnormalities are the basis for the diagnostic sweat test, characterized by elevated sodium, potassium, and chloride levels in sweat.
Lung involvement is commonplace and is usually the cause of death. Bronchial gland hypertrophy with mucous plugging and small-airway obstruction leads to subsequent infection that ultimately causes chronic bronchitis and bronchiectasis. For complex and not completely explicable reasons, chronic inflammation from Pseudomonas aeruginosa occurs in more than 90 percent of patients. In a minority,aS aureus, H inluenzae, and Burkholderia cepacia are recovered (Rowe, 2005). Colonization with the last has been reported to signiy a worse prognosis, especially in pregnancy (Gillet, 2002). Acute and chronic parenchymal inlammation ultimately causes extensive fibrosis, and along with airway obstruction, ventilation-perfusion mismatch develops. Pulmonary insuiciency is the end result. Lung or heart-lung transplantation has a 5-year survival rate of only 50 to 60 percent (Sorscher, 2015). A few women have successfully undergone pregnancy following lung transplantation (Kruszka, 2002; Shaner, 2012).