Patterns of GI disease in adulthood associated with mutations in the CFTR gene.
There has been tremendous growth in the population of adults with cystic fibrosis (CF). This demographic change has created the need for special clinics to care for adults with CF and has resulted in an awakening of interest in CF among physicians caring for adults. The protean and varied manifestations of CF disease in multiple organs call for expanded knowledge of the condition among physicians in a wide variety of subspecialties, including, but not limited to, pulmonary medicine, gastroenterology, hepatology, clinical nutrition, endocrinology, infectious diseases, rheumatology and andrology. This review will focus on disease pathobiology of the gastrointestinal and hepatic manifestations of CF disease which the internist is likely to encounter.
We will first examine the clinical manifestations of CF disease that are directly associated with loss of function of the cystic fibrosis transmembrane regulator (CFTR) protein and then summarise those which are secondary. We will elaborate the challenges of establishing or excluding a CF diagnosis in patients who present de novo in adulthood, with particular attention to conditions with CF?like phenotypes that are associated with an increased frequency of mutations in the CFTR gene. Finally, we will briefly discuss emerging knowledge of the potential contribution of mutations in the CFTR gene to other complex genetic conditions.
Over the past three decades the most striking result of advances in the care of patients with CF has been the dramatic improvement in survival. Whereas median survival in the United States was only 16?years in 1970, it has risen to over 32?years in 2005. For patients born in the 1990s median survival is predicted to exceed 40?years. Of patients born in the United Kingdom in 1980, 82% were alive at age 20, whereas for children born in 1990, 96.5% are alive at age 15. As a consequence, there has been a striking increase in the number and proportion of adults with CF disease. For example, this decade the proportion of patients with CF over the age of 18 in the United States has reached 40%, whereas in 1970 it was only 10% of the CF population. In other developed nations the proportion of adults in the CF population is similar to, or even greater than, those reported in the US CF patient data registry. In the UK, the percentage of adult patients reached 50.8% in 2003 (UK CF database). This demographic change is largely attributable to improved survival of patients diagnosed in infancy and childhood, mainly owing to advances in nutritional and respiratory care. Furthermore, with advances in our understanding of the heterogeneity and spectrum of CF disease, together with improved awareness among internists, an increasing number of patients are being diagnosed de novo in adulthood. Both these factors have shifted the burden of illness to the third and fourth decades of life and beyond. With improvement in survival, the natural history of the disease is changing and new, hitherto unknown, complications are emerging.