Cystic fibrosis: Diagnostic considerations

With an estimated incidence as high as 1:2000 in caucasians, cystic fibrosis (CF) is the most common lethal inherited disorder in the United States. The condition also occurs in 1 of 17,000 American blacks and has been reported rarely in American Indians and orientals. The major clinical features are exocrine pancreatic insufficiency, chronic obstructive pulmonary disease and increased loss of electrolytes in the sweat. The basic defect is unknown, but most of the clinical manifestations can be related to obstruction of organ passages by mucus secretions which exhibit abnormal physicochemical behavior. Screening for CF in the newborn period has been advocated based on the observation of improved outcome with early intervention as a means of providing information for genetic counseling, and for purposes of enumeration and research. The sweat test has not been useful for screening because of expense and difficulty in obtaining an adequate quantity of sweat in the newborn period. The most widely used screening tests are those based on the presence of increased amounts of protein in meconium secondary to deficiency of pancreatic proteolytic enzymes. Protein can be detected semiquantitatively with a test strip or by a radial immunodiffusion technique. These tests will not identify those patients with residual pancreatic function. There may be false-positive values in the presence of prematurity and melena, and false-negative values have been reported in patients with pancreatic insufficiency. A recently proposed screening procedure involved the use of dried blood spots for assay of immunoreactive trypsin, which may be increased in the early stage of CF, including patients with residual pancreatic function.