Cystic Fibrosis

• Hereditary metabolic disorder common among white

populations – Autosomal Recessive
• Defective CFTR (cystic fibrosis transmembrane conductance
regulator)
• The most common mutation is ΔF508 (absence of
phenylalanine) mutation on chromosome 7
• Mutated CFTR gene → misfolded protein → retained protein
in RER that is unable to reach the cell membrane  →
defective chloride channel → inability to transport
intracellular chloride ions across the membrane → exocrine
glands (pancreas) produce hyperviscous
secretions  → accumulation of secretions and blockage
of exocrine glands  → chronic inflammation  organ damage
 Clinical Features
• Respiratory symptoms
– recurrent pulmonary infections  Bronchoectasias
• Pseudomona, S. aureus, Burkholderia Cepacia
– chronic sinusitis
• Gastrointestinal symptoms
– chronic, frequent diarrhea
• greasy stool with flatulence from malabsorption secondary to pancreatic
insufficiency
• can lead to rectal prolapse
– meconium ileus in infants (15%) 
– pancreatitis 
• Other features – Digital clubbing, Nasal polyps, Salty skin,
Infertility in men(absence of vas deferens), Subfertility in
women (thick cervical mucus)
 Diagnosis
• Sweat chloride test - historical diagnostic gold
standard
– >60 mEq/L in patients <20 years old
– >80 mEq/L in adults
• Immunoreactive trypsinogen assay
• Increased Nasal transepithelial potential
difference
 Treatment

• chest physiotherapy (percussion, positive pressure,

nebulizers)
• bronchodilators
• inhaled corticosteriods 
– if asthmatic
• DNA-ase and hypertonic saline
– antibiotics 
• chronic macrolide therapy common
• IV antibiotics for acute exacerbations
– anti-inflammatory agents (ibuprofen)
• pancreatic enzymes and fat-soluble vitamins
• A 1-year-old child who was born outside of the United States is
brought to a pediatrician for the first time because she is not
gaining weight. Upon questioning, the pediatrician learns that the
child has had frequent pulmonary infections since birth, and on
exam the pediatrician appreciates several nasal polyps. Genetic
testing is subsequently ordered to confirm the suspected diagnosis.
Testing is most likely to show absence of which of the following
amino acids from the protein involved in this child's condition? 
• A. Histidine
• B. Leucine
• C. Lysine
• D. Valine
• E. Phenylalanine
• A newborn is found to have cystic fibrosis during routine newborn
screening. The parents, both biochemists, are curious about the
biochemical basis of their newborn's condition. The pediatrician
explains that the mutation causing cystic fibrosis affects the CFTR
gene which codes for the CFTR channel. Which of the following
correctly describes the pathogenesis of the most common CFTR
mutation?

• A. Insufficient CFTR channel production

• B. Defective post-translational glycosylation of the CFTR channel
• C. Excess CFTR channel production
• D. Defective post-translational hydroxylation of the CFTR channel
• E. Defective post-translational phosphorylation of the CFTR channel
• A 1-year-old male with a history of recurrent pseudomonal
respiratory infections and steatorrhea presents to the pediatrician
for a sweat test. The results demonstrate a chloride concentration
of 70 mEq/L (nl < 40 mEq/L). Which of the following defects has a
similar mode of inheritance as the disorder experienced by this
patient?
• A. Trinucleotide repeat expansion of CAG on chromosome 4
• B. Accumulation of glycogen in the lysosome
• C. Inability to convert carbamoyl phosphate and ornithine into
citrulline
• D. Abnormal production of type IV collagen
• E. Mutated gene for mitochondrial-tRNA-Lys
• A 27-year-old female presents to general medical clinic for a routine
checkup. She has a genetic disease marked by a mutation in a chloride
transporter. She has a history of chronic bronchitis. She has a brother
with a similar history of infections as well as infertility. Which of the
following is most likely true regarding a potential vitamin deficiency
complication secondary to this patient's chronic illness?

• A. It may result in connective tissue defects

• B. It may result in corneal vascularization
• C. It may result in the triad of confusion, ophthalmoplegia, and ataxia
• D. It may be exacerbated by excessive ingestion of raw eggs
• E. It may manifest itself as a prolonged PT
• A 4-year-old Caucasian girl previously diagnosed with
asthma presents with recurrent sinusitis, otitis media, and
clubbing of the nail bed. Family history is significant for a
distant cousin with cystic fibrosis. A "sweat test" is
performed and comes back normal. What additional
diagnostic test would be helpful in establishing a diagnosis?
• A. Nasal transepithelial potential difference
• B. Chest radiograph
• C. Skeletal survey
• D. Complete blood cell count
• E. Urinalysis