Wallach's Interpretation of Diagnostic Tests: Pathways to Arriving at a Clinical Diagnosis (450 page)

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CYSTIC FIBROSIS AND RELATED DISORDERS

MIM #219700

   Definition

Cystic fibrosis (CF) is an autosomal recessive disorder with abnormal ion transport caused by mutations in the cystic fibrosis conductance regulator gene (CFTR) located on chromosome 7 that commonly affect the lungs and digestive system of patients. CF is the most common genetic disease in the Caucasian population in the United States. The disease occurs in 1 in 2,500–3,500 Caucasian newborns. CF is less common in other ethnic groups, affecting about 1 in 17,000 African Americans and 1 in 31,000 Asian Americans. Cystic fibrosis affects the epithelia of the respiratory tract, exocrine pancreas, intestine, male genital tract, hepatobiliary system, and exocrine sweat glands, resulting in complex multisystem disease. Respiratory symptoms include fatigue, cough, wheezing, recurrent pneumonia or sinus infections, excess sputum, and shortness of breath. Mutations in the CFTR gene can also cause congenital absence of the vas deferens (CAVD).

   Diagnostic Criteria for CF

   Presence of two disease-causing mutations in CFTR.

   Sweat chloride values (>60 mEq/L) accurately diagnosis approximately 90% of cases.

   Transepithelial nasal potential difference (NPD) measurements characteristic of CF.

   In newborn screening, immunoreactive trypsinogen (IRT) assays are performed on blood spots; abnormal IRT results are further evaluated through sweat testing and/or molecular genetic testing of the CFTR gene.

   Diagnostic Criteria for CAVD

   Azoospermia

   Low volume of ejaculated semen

   Absence of the vas deferens on clinical or ultrasound examination

   And at least one disease-causing mutation in the CFTR gene

   Relevant Tests

   Quantitative pilocarpine iontophoresis for sweat chloride concentrations remains the primary test for the diagnosis of CF.