Ninety percent of patients with CF are born with exocrine pancreatic insufficiency. The inspissation of mucus and subsequent destruction of the pancreatic ducts result in the inability toexcrete pancreatic enzymes into the intestine. This leads to malabsorption of proteins, sugars (to a lesser extent), and especially fat. Fat malabsorption manifests clinically as steatorrhea (largefoul-smelling stools), deficiencies of fat-soluble vitamins (A, D,E, and K), and failure to thrive. Protein malabsorption can present early in infancy as hypoproteinemia and peripheral edema.Approximately 10% of patients with CF are born with intestinal obstruction caused by inspissated meconium (meconium ileus). In older patients, intestinal obstruction may result fromthick inspissated mucus in the intestinal lumen (distal intestinal obstruction syndrome). In adolescent or adult patients,progressive pancreatic damage can lead to enough islet celldestruction to cause insulin deficiency. This initially presentsas glucose intolerance, but true diabetes that requires insulintherapy (CF-related diabetes) may develop. The failure of thesweat ducts to conserve sodium and chloride may lead to hyponatremia and hypochloremic metabolic alkalosis, especially ininfants. Inspissation of mucus in the reproductive tract leads toreproductive dysfunction in both males and females. In males,congenital absence of the vas deferens and azoospermia arenearly universal. In females, secondary amenorrhea is oftenpresent as a result of chronic illness and reduced body weight.Fertility is also diminished by abnormal secretions in the fallopian tubes and cervix, but women with CF can conceive.
All infants with a positive newborn screen and/or with meconium ileus should be evaluated for CF. The diagnosis of CF should be seriously considered in any infant presenting with failure to thrive, cholestatic jaundice, chronic respiratory symptoms, or electrolyte abnormalities (hyponatremia, hypochloremia, metabolic alkalosis). CF should be in the differential diagnosis of children with chronic respiratory or gastrointestinal symptoms, especially if there is digital clubbing. Any child with nasal polyps, especially those younger than 12 years, should be evaluated for CF. All siblings of patients with CF should also be evaluated.
Readily available commercial DNA tests detect many CF mutations, but because there are more than 1500 identified mutations (and others yet to be identified), DNA analysis will not detect all cases of CF. All U.S. states have newborn screening for CF, based either on elevated immunoreactive trypsinogen (IRT) levels or DNA tests, identifying the majority of infants with CF, but there are both false-positive and false-negative results. Therefore, the diagnostic test of choice is still the sweat test. Indications for performing a sweat test are listed in Table 137-2. The following criteria should be met to establish the diagnosis of CF:The presence of one or more typical clinical features of CF (chronic pulmonary disease, characteristic gastrointestinal and nutritional abnormalities, salt loss syndromes, or 1.
Two elevated sweat chloride tests performed at an accredited CF Foundation certified laboratory (positive if the value is >60 mEq/L, borderline if 40 to 60 mEq/L, and negative if <40mEq/L, with adequate sweat collection) 2.
Two mutations known to cause CF identified by DNA analysis or 3.
because a sibling has CF, positive sweat chloride testing or the
Recurrent wheezing/difficult to control asthma Recurrent or persistent atelectasis Hemoptysis Pseudomonas aeruginosa in the respiratory tract (if not explained by other factors, e.g., tracheostomy or prolonged intubation)