Cystic fibrosis

Abstract

Over 7000 people have cystic fibrosis in the United Kingdom.It is the commonest genetically inherited disease in white populations (1 in 2500 newborns), although it is increasingly recognised as being important in non-white populations.However, most general practitioners have only one or two patients on their list, and as management generally takes place in specialist centres, many general paediatricians will be involved in the care of only a small number of patients.Progress in our understanding of the disease and the impact of this on management has been rapid over the past 20 years.Cystic fibrosis used to be a digestive and lung disease of young children but more recently has become a complex, multisystem disease extending into adulthood; there will soon be more adults than children with the condition.The predicted median survival for babies born in the 21st century is now more than 50 years.1 This increased survival-together with changes in standard treatment, the increasing implementation of newborn screening, and the focus on new therapeutic strategies-leads us to consider that an update on this albeit relatively rare disease may be of general interest. What is the cause of cystic fibrosis?Cystic fibrosis is an autosomal recessive disease.It is caused by mutations in the CFTR (cystic fibrosis transmembrane conductance regulator) gene. 2 The commonest mutation is the deletion of phenylalanine at codon 508 (phe508del, until recently known as ΔF508).This occurs in about 70% of patients with cystic fibrosis (www.ornl.gov/sci/techresources/Human_Genome/posters/chromosome/cftr.shtml).Over 1600 mutations of the CFTR gene have been described.Different mutations in this gene have varying effects on CFTR function and can result in different phenotypes of the disease.Some mutations will result in milder forms of the disease, although there is not enough evidence about these rarer mutations to counsel patients about their prognosis.The CFTR protein is expressed in many cells and has several functions, not all of which have been linked with disease.The primary function of the CFTR protein is as an ion channel that regulates liquid volume on epithelial surfaces through chloride secretion and inhibition of sodium absorption.