Cystic fibrosis (CF) is a multisystem disease affecting the gastrointestinal, respiratory, and reproductive tracts and the sweat glands. It is the most common life-shortening autosomal recessive disorder in the Caucasian population, affecting approximately 1 in 2500 to 3300 live births. However, CF occurs among persons of all races and ethnicities. Although the classic CF triad is chronic obstructive lung disease, exocrine pancreatic insufficiency, and sweat gland abnormalities, CF can mimic many other common pediatric conditions. Its presentation can vary from classic CF with severe manifestations early in life to later presentations with mild or even atypical symptoms.1-4 In 2009, newborn screening for CF became mandatory in all 50 states.5-7 With the implementation of universal newborn screening for CF, clinical care guidelines were developed to aggressively identify and address respiratory and nutritional problems prior to the development of symptoms.8-11 Each of these factors has relevance to the pediatric hospitalist, who may evaluate and treat patients with chronic respiratory or gastrointestinal symptoms in which the differential diagnosis includes CF or manage disease-related complications in individuals with known CF.
CF is caused by mutations in a single gene on the long arm of chromosome 7 that encodes for the cystic fibrosis transmembrane conductance regulator (CFTR) protein.12 More than 1600 CFTR mutations have been identified of which at least 200 cause disease;12 six functional classifications have been devised to better understand the implications of specific gene abnormalities (Table 144-1). Despite the sheer number of CFTR mutations that lead to clinical disease (CF), there is a single mutation, F508del, that accounts for approximately 70% of affected alleles.1-4 The F508del mutation results in the deletion of phenylalanine in the 508 position of the CFTR protein and is an example of a class 2 mutation (see Table 144-1).
TABLE 144-1CFTR Mutations ||Download (.pdf) TABLE 144-1 CFTR Mutations
|Class ||CFTR Defect ||Examples |
|1 ||No CFTR protein synthesis ||W1282X, G542X |
|2 ||Block in processing of CFTR ||ΔAF508, N1303K |
|3 ||Improper regulation of CFTR ||G551D, G551S |
|4 ||Abnormal conduction through CFTR ||R117H, R334W |
|5 ||Reduced synthesis and/or mistargeting of CFTR ||A455E, Q1412X |
|6 ||Increased turnover of CFTR at the cell surface ||N287Y |
The CFTR protein functions as a chloride channel in the apical membrane of cells.1-3 In addition, it affects other apical membrane conductance pathways. CFTR is expressed in the cells of affected organs, including the respiratory and intestinal epithelia, pancreatic ducts, hepatobiliary tract, and sweat ducts. It is believed that the loss of function of the CFTR ion channel in CF results in abnormal ion and fluid movement across epithelial membranes, which leads to abnormal secretions in the affected organs.1-4,13 These abnormalities can lead to inspissated mucus and obstruction of glandular ducts, inflammation, and eventual organ destruction. In the lung, it can lead to a slower ...