[Cystic fibrosis from the exocrine pancreatic point of view].
Cystic fibrosis (CF) is the most common life-limiting autosomal recessive genetic disorder in Caucasians and is characterized by a wide variability of clinical expression. The vast majority of patients with CF have pancreatic insufficiency (PI) requiring exogenous pancreatic enzyme replacement therapy with meals. It is caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene, which encodes a protein that functions as a chloride channel and is regulated by cAMP. CFTR gene mutations may be classified as severe or mild with respect to pancreatic function status. Patients homozygous for two severe mutations experience severe clinical presentation including PI. Patients carrying at least one mild mutation are considered to be pancreatic sufficient (PS) and carry an overall prognosis that is vastly superior to CF patients with PI. Thus mild mutations appear to be dominant, providing enough functional CFTR to avoid PI. Five general mechanisms have been proposed which describe how CFTR gene mutations influence CFTR-mediated chloride secretion. Classes 1, 2, and 3. that confer little or no chloride channel function, confer the PI phenotype. In contrast, classes 4 and 5 allow CFTR residual function, that are expected to confer the less severe PS phenotype. Recent advances in mutation detection technology and the demonstration of characteristic abnormalities in trans-epithelial potential difference measurements, have expanded the spectrum of diseases associated with the CFTR mutant genes, and paradoxically, in some ways complicated rather than simplified CF diagnosis. Until new diagnostic criteria is conclusively determined, CF diagnosis should be made on clinical rather than laboratory grounds.
Virgilis
Dov
D
Clalit Health Services, Sharon-Shomron District, Hadera Child Health Center, Israel.
D003550:Cystic Fibrosis / Q000188:drug therapy / Q000235:genetics / Q000503:physiopathology*; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000235:genetics; D057487:Enzyme Therapy; D004798:Enzymes / Q000008:administration & dosage; D006801:Humans; D009154:Mutation; D010179:Pancreas / Q000201:enzymology / Q000503:physiopathology*
C505032:CFTR protein, human; D004798:Enzymes; D019005:Cystic Fibrosis Transmembrane Conductance Regulator