Cystic Fibrosis: Carrier Testing, Newborn Screening, and Diagnostic Testing

Abstract

Cystic fibrosis (CF) is the most common life-shortening autosomal recessive genetic disorder in the Caucasian population. CF is due to mutations in the cystic fibrosis transmembrane regulator (CFTR) gene, located on chromosome 7 at 7q31.2, which encodes a cyclic AMP-activated chloride channel [1, 2]. The disorder has a broad range of severity, but classical CF is manifested by chronic pulmonary disease, exocrine pancreatic insufficiency, and elevated concentrations of chloride in sweat. Approximately 85 % of individuals with CF do not retain sufficient exocrine pancreatic function to adequately digest food. Thus, without oral pancreatic enzyme supplementation, severe malnutrition and growth failure can occur within the first years of life. The major cause of morbidity and mortality in CF is the chronic, suppurative pulmonary disease. The CF lung is extremely susceptible to infection, particularly with the mucoid form of the gram negative bacterium Pseudomonas aeruginosa and the gram-positive Staphylococcus aureus [3]. Although the details are still unclear, the mechanism of the lung disease is thought to originate in the relative lack of airway surface hydration due to abnormal sodium and chloride transport and the associated movement of water across the apical epithelia. The dehydrated mucus lining the airways becomes difficult for the cilia to move and clear trapped particulate matter, including inhaled bacteria. Subsequent bacterial growth stimulates inflammation and mucus hypersecretion, which in turn becomes dehydrated and difficult to expel. Thus, there is cycle of increasing pulmonary obstruction and inflammation that leads, without treatment, and in some cases, in spite of treatment, to bronchiectasis and end-stage lung disease [4].