1.1 Clinical Aspects of Cystic Fibrosis: Cystic fibrosis (CF) is the most common lethal 
autosomal recessive disease that affects the Caucasian population (Boat et.al., 1989; Wood et.al., 
1976). Cystic fibrosis has an estimated incidence in the white population of between one in 
2,000 and one in 2,500. This disease also affects other ethnic groups, such as the North 
American black population, with an incidence of one in 17,000, and the native American 
population with an approximate incidence of one in 80,000. The basic defect of cystic fibrosis 
is an abnormality of cAMP regulated chloride secretion by epithelial cells, affecting exocrine 
glands and the lungs. The disease in characterized by abnormal secretions in the respiratory, 
gastrointestinal, and reproductive tracts and in the sweat glands. The failure of cAMP 
stimulated chloride secretion by epithelial cells leads to dehydration of secretions which are too 
viscid or too concentrated. Cystic fibrosis is manifested in the lung by obstructive pulmonary 
disease with chronic infection, in the gastrointestinal tract by exocrine pancreatic insufficiency 
leading to malabsorption, in the intestines where abnormal secretions result in small bowel 
obstruction, in the liver where focal biliary cirrhosis may develop, in the vas deferens resulting 
in obstructive azoospermia, and by the sweat glands, causing increased secretion of NaCl. 
Cystic fibrosis is inherited as an autosomal recessive disease, and the gene is located on the 
long arm of Chromosome 7 at position 7q31 (Rommens et.al., 1989; Riordan et.al., 1989; 
Kerem et.al., 1989). At the time of writing, more than 200 mutations have been recognized at 
this locus (Collins FS, personal communication !. 
For couples affected by cystic fibrosis, there is a one in four risk of have an affected child 
in each subsequent pregnancy. It is now feasible to perform limited genetic analysis for prenatal 
diagnosis, heterozygote detection, diagnosis of atypical cases, and for genetic counseling. 
The laboratory diagnosis of cystic fibrosis is based on analysis of sweat collected by the 
quantitative pilocarpine iontophoresis method of Gibson and Cooke (1959). Samples of sweat 
for analysis should weigh at least 100 mg; a concentration of chloride greater than 60 meq/1 is 
diagnostic for cystic fibrosis. A false negative sweat test can be found in the presence of edema 
or hypoproteinemia. A false positive result can be obtained with malnutrition, laboratory error, 
and various metabolic and endocrine conditions. 
The presentation of cystic fibrosis is usually with a combination of diarrhea, recurrent 
respiratory infections, and failure to thrive. There are many less common presentations of which 
the most important is small intestinal obstruction by thick inspissated meconium. These children 
usually present in the first day or two of life with abdominal distention, bile stained vomiting, 
and delayed passage of meconium. Other presentations of cystic fibrosis include rectal prolapse, 
nasal polyps, prolonged neonatal jaundice, hypochloremic alkalosis with dehydration, 
hepatomegaly, and a syndrome of anemia, edema, and hypoproteinemia (Boat et.al., 1989; 
Wood et.al., 1976). 
Although there is a generalized disorder of exocrine secretion in cystic fibrosis, the lungs 
take the brunt of this disease and account for most of the morbidity and mortality (Wood et.al., 
1976). The clinical progression of cystic fibrosis is very variable. Some children have mainly 
pulmonary disease while others have mainly malabsorption. The disease does not breed true 
in families and subsequent children in one family may have different presentations, different 
manifestations, and different degrees of severity. It has been reported that the most common 
mutation for cystic fibrosis, the deletion of phenylalanine at position 508 of the CFTR protein, 
is strongly associated with pancreatic insufficiency (Kerem et.al., 1990). Other mutations appear 
to be associated with pancreatic sufficiency and with a milder phenotype. In spite of this 
variation in phenotype, progressive obstructive pulmonary disease eventually develops in all CF 
patients. The earliest changes are gas trapping, as shown by an increased residual volume and 
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