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
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.
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.
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.
Table 514-1. Characteristics
of Various CFTR Mutations |Favorite Table|Download (.pdf)
Table 514-1. Characteristics
of Various CFTR Mutations
|ΔF508||70–75% in North America||Pancreatic insufficiency||II|
|W1282X||50–60% in Ashkenazi Jews; 2% worldwide||Pancreatic insufficiency||I|
|G542X||3.4% worldwide||Pancreatic insufficiency||I|
|G551D||2.4% worldwide||Pancreatic insufficiency||III|
|3905insT||2.1% worldwide||Pancreatic insufficiency||I|
|N1303K||1.8% worldwide||Pancreatic insufficiency||II|
|R553X||1.3% worldwide||Pancreatic insufficiency||I|
|621 + 1G → T||1.3% worldwide||Pancreatic insufficiency|
|1717 – 1G → T||1.3% worldwide||Pancreatic insufficiency|
|A455E||3–7% in Netherlands; 0–0.2% in North
America||Pancreatic sufficiency; mild lung disease||IV|
|3849 + 10kb C → T||1.4% worldwide; 4% in Israel...|
Log In to View More
If you don't have a subscription, please view our individual subscription options below to find out how you can gain access to this content.
Want remote access to your institution's subscription?
Sign in to your MyAccess profile while you are actively authenticated on this site via your institution (you will be able to verify this by looking at the top right corner of the screen - if you see your institution's name, you are authenticated). Once logged in to your MyAccess profile, you will be able to access your institution's subscription for 90 days from any location. You must be logged in while authenticated at least once every 90 days to maintain this remote access.
If your institution subscribes to this resource, and you don't have a MyAccess profile, please contact your library's reference desk for information on how to gain access to this resource from off-campus.
AccessPediatrics Full Site: One-Year Subscription
Connect to the full suite of AccessPediatrics content and resources including 20+ textbooks such as Rudolph’s Pediatrics and The Pediatric Practice series, high-quality procedural videos, images, and animations, interactive board review, an integrated pediatric drug database, and more.
Pay Per View: Timed Access to all of AccessPediatrics
24 Hour Subscription $34.95
48 Hour Subscription $54.95
Pop-up div Successfully Displayed
This div only appears when the trigger link is hovered over.
Otherwise it is hidden from view.