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Cystic fibrosis (CF) is the most common profoundly life-shortening
inherited disease in North America. In 1938, Dr. Dorothy Andersen
first described the complex of respiratory and digestive signs and
symptoms that make up this syndrome,1 but references
to a childhood disorder characterized by salty sweat and early death
date back to at least the Middle Ages. The cellular and molecular
bases for the disorder have recently been elucidated.2,3
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Cystic fibrosis (CF) is inherited as an autosomal recessive disorder.
It is most common in those of northern European descent, with an
incidence of approximately 1 in every 3200 live births. It is seen
in about 1 in every 17,000 births in African Americans and is much
less common in Asian populations. It has been found in virtually
every ethnic and racial group. Approximately 4% of whites
are heterozygous for CF (ie, carry one CF allele); heterozygotes
have no evidence of clinical disease.
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Pathophysiology
and Genetics
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CF affects virtually every organ system with epithelial surfaces—most
importantly, the lungs, pancreas, intestinal mucus glands, liver,
the reproductive tracts, and sweat glands. A common pathogenetic
mechanism in major target systems is abnormal ion transport across
epithelial surfaces. Impermeable chloride channels and overactive
sodium pumps of these epithelial cells lead to biochemical and bioelectric
abnormalities within organ lumina, leading in turn to viscid intralumenal
secretions in the affected organs. These abnormally viscous secretions
cause the blockage of ducts and air passages.
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The most common mutation in the CF gene is a three-base-pair
deletion that leads to the loss of a single phenylalanine at position
508 of the protein product (“ΔF508”).4 The ΔF508
mutation accounts for 70% to 80% of CF chromosomes;
about 50% of CF patients in North America are homozygous
for this mutation. More than 1500 other mutations at the CF locus
have been discovered, but these account for only a small percentage
of CF cases. In a few ethnic groups, a small number of mutations
account for a large proportion of CF cases (Table
514-1). Prenatal testing and carrier testing can be accomplished
in virtually every family desiring this information.
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