Cystic Fibrosis (CF)

Cystic fibrosis is a recessively inherited disease involving the chloride channels in the apical membrane of epithelial cells. It is characterised principally by pancreatic and respiratory dysfunction. One in every 2,500 babies has CF. One in every 25 people in the NSW population is a carrier of CF. CF is commonest in persons of a Northern European background, but it is also relatively common in Mediterranean and Middle Eastern populations and possibly in parts of India. Early diagnosis and treatment are important, as recent medical and scientific advances have greatly improved the outlook for babies with CF.

The most common mutation in the CF gene, CFTR, which causes the disorder of cystic fibrosis is a three-base-pair deletion resulting in the loss of a phenylalanine residue at position 508. This mutation is called F508.

Clinical features:

Cystic fibrosis is classically characterised by the triad of pancreatic insufficiency, recurrent and eventually chronic lung disease, and increased sweat electrolytes. The pancreatic disease causes meconium ileus (a bowel blockage) in about 20% of CF babies. It is also responsible for fatty motions, failure to thrive, and various specific nutritional deficiencies. Approximately 10% of CF patients show only partial pancreatic insufficiency, and retain enough function to prevent the syndrome of malabsorption. The respiratory disease is associated with thick and sticky mucus, causing a suppurative lung disease. The disease is almost invariably associated with elevated levels of electrolytes in the sweat, and this has been used as a definitive test.

Laboratory tests:

The initial screening test measures immunoreactive trypsin (IRT) in the blood sample. The 1% of samples with the highest IRT are further investigated by a mutational analysis for F508 deletion. Babies who are homozygous for F508 are referred to a CF clinic. Babies who are heterozygous for F508 are referred for sweat testing to an experienced sweat testing laboratory.

Treatment:

Treatment of CF is complex, and needs to be assessed for each individual. There are two main areas of treatment strategy: those dealing with pancreatic insufficiency and poor nutrition, and those concerned with improvement of lung function.

Screening considerations:

Detection of CF in the neonate depends on the presence of an elevated IRT concentration in the blood sample, followed by a DNA analysis of samples with high IRT values. In babies with meconium ileus the IRT levels may not be very elevated. Therefore, information about meconium ileus should be indicated on the sample card to ensure that mutation analysis is carried out, even if the IRT falls into the normal range.