Congenital multiorgan disease affecting mainly the
lungs, liver, and pancreas. Frequent lung infections, hemoptysis,
intolerance to exercise, presence of clubbing fingers suggesting pulmonary
hypertension, rectal prolapse, and nasal polyps.
In the United States, CF is the most common lethal
disease inherited in the white population. In America and Northern European
origin, the prevalence is estimated at 1:3000. In African Americans, the
prevalence is 1:15,000 whereas in hispanics, it is estimated at 1 case
per 9200. In Asian Americans, the prevalence is reported at 1 case per 31,000.
Autosomal recessive. More than 1000
mutations have been described on the long arm of chromosome 7
(7q21.3-7q22.1); the most frequent is ΔF508, which results in a
defect of the CF transmembrane regulator protein called CFTR.
Malfunction of the gene coding for the CF transmembrane conductance
regulator (CFTR) protein causes defective cAMP-dependent chloride secretion from the epithelium
of different exocrine tissues, leading to thick viscous and difficult-to-clear
secretions in lungs, sinuses, pancreas, intestine, liver, and reproductive tract. In
addition, the CFTR-mediated regulation of sodium channel activity may fail, leading to
increased sodium absorption from the airways, which contributes to the fluidity and mobilization of
the airway secretions. Also, hyperplastic airway epithelium with areas of erosion and
squamous metaplasia of the submucosal glands leads to plug of mucoid material and subsequently
to the release of inflammatory cells. Eventually, grossly dilated airways with purulent secretions
are observed and severely congested parenchyma develops. Radiologic findings reflect the pathologic changes in the airways. Although the lungs of infants born with CF
are structurally normal at birth, respiratory symptoms are usually the first sign of CF.
Difficult in children. Depends on the clinical history
and a high index of suspicion together with a family history of the disease;
a high sweat sodium concentration greater than 60 mmol/l, or abnormal in vivo nasal
potential difference. A normal nasal potential difference value is 0. 9-24.7 mV, whereas an abnormal measurement is 1.8-53 mV (difference of
potential voltage difference between the nasal mucosa and a reference electrode into the forearm).
Absent vas deferens and epididymis in the male. Immunoreactive
CF is now the most common cause of recurrent
bronchopulmonary infection in childhood and is an important cause in early
adult life. Finger clubbing is almost universal, hemoptysis is frequent, and
breathlessness occurs in the later stages as airflow limitation develops.
Older children may develop nasal polyps. Gastroesophageal reflux is often
present. Puberty and skeletal maturity are delayed in most patients with the
disease. Males are always infertile as a result of failure of development of
the vas deferens and epididymis. Females are able to reproduce, but often
develop secondary amenorrhea as the disease progresses. Approximately 85%
of patients have symptomatic steatorrhea because of pancreatic dysfunction.
Children may be born with meconium ileus because of the viscoid consistency
of meconium in CF and later in life develop the ...