What Is a Cystic Fibrosis Diagnosis?

Cystic fibrosis (CF) is the most common life-limiting genetic disorder in whites, with an incidence of 1 in 3200 newborns in the United States. 46 It is less common in African Americans (1 in 15,000) and Asian Americans (1 in 31,000), but the diagnosis needs to be considered in patients of diverse racial and ethnic backgrounds. 46 , 116 Although CF is a well-characterized genetic disorder, it remains a clinical diagnosis suggested by phenotypic (clinical) features (Table 1) and, in most cases, confirmed by demonstration of an elevated concentration of electrolytes in the sweat. 116 It is marked by great variability in the frequency and severity of clinical manifestations and complications. The possibility of CF should never be discounted because of how well a patient appears. In 70% of cases, the diagnosis is established prior to age 1 year, usually within the first several months of life. 30 In 8% of patients, however, the diagnosis is not established until after age 10 years, and the diagnosis is being made in an increasing number of adults. Almost all patients have chronic sinopulmonary disease and, in postpubertal men, obstructive azoospermia. 116 Approximately 90% of patients have exocrine pancreatic insufficiency, whereas the remainder are pancreatic sufficient. 116 The subset of patients with pancreatic sufficiency is characterized by milder clinical course, better nutritional status, better pulmonary function, and a distinctly later age at diagnosis. 33 In recent years, the ability to detect CF mutations and to measure transepithelial bioelectric properties has greatly expanded the CF clinical spectrum. An “atypical” phenotype in which there is chronic sinopulmonary disease, pancreatic sufficiency, and either borderline (40 to 60 mmol/L) 6 , 101 or normal (<40 mmol/L) 49 , 105 sweat chloride concentrations exists in approximately 2% of patients. In addition, there are patients in whom a single clinical feature—for example, electrolyte abnormalities, 66 pancreatitis, 5 , 96 liver disease, 102 sinusitis, 117 or obstructive azoospermia—predominates. 3 , 14 , 16 , 54 , 78 The frequencies of common presenting manifestations among patients reported to the United States Cystic Fibrosis Foundation Data Registry are shown in Table 2. In most cases, the family history is negative for CF.