Features

  • 2 major phenotypes
    • Typical CF: chronic sinopulmonary infection, nasal polyps (10-32%), hepatobiliary disease, pancreatic insufficiency, meconeum ileus at birth, elevated sweat chloride values, obstructive azoospermia
    • Atypical CF: as above, except sweat chloride is normal or borderline, and there is no meconeum ileus, pancreatic insufficiency, hepatobiliary disease
  • Lung disease may be complicated by ABPA
  • Frequency
    • 50% of children (4-16 years old) presenting with nasal polyps have CF
    • 1 in 2,500–3,500 Caucasian Americans
    • 1 in 4,000–10,000 Hispanic Americans
    • 1 in 15,000–20,000 African Americans
    • 1 in 100,000 Asian Americans



Diagnosis

  • AR mutation in CFTR chloride channel gene (>1000 mutations identified), affecting 1/3700 births, most common in (but not restricted to) Caucasians
  • Diagnostic criteria:
One of these:
--plus--
one of these:
1 typical phenotypic features of CF-----

Elevated sweat chloride test on 2 occasions-----
Sibling with CF

2 identified CFTR mutations
Positive newborn screening test (IRT)

Abnormal nasal potential difference (at research centers)
  • Newborn screen tests for immunoreactve trypsinogen (IRT) level which is 2-5 times higher in CF due to leakage of pancreatic secretions into the circulation caused by blocked pancreatic ducts
    • If IRT abnormal, some states confirm with repeat IRT, others perform DNA test

  • Sweat chloride test (quantitative pilocarpine iontophoresis) - diagnostic gold standard if done at an accredited CF center
    • Results
      • <40 mmol/L - negative
      • 40-60 mmol/L = borderline (infants <6 months can have lower values, therefore 30-60 considered borderline)
      • >60 mmol/L - positive
      • Note that some mutations (atypical CF) are associated with normal sweat test (~1% with CF have normal sweat chloride)
    • Diseases other than CF with elevated sweat chloride:
      • Adrenal insufficiency
      • Pseudohypoaldosteronism
      • Hypothyroidism
      • Hypoparathyroidism
      • Nephrogenic diabetes insipidus
      • Ectodermal dysplasia
      • Glycogen storage disease (type I)
      • Mucopolysaccharidoses
      • Fucosidosis
      • Malnutrition
      • Mauriac syndrome
      • Familial cholestasis syndrome
      • Pancreatitis
      • Prostaglandin E1 administration
      • Hypogammaglobulinemia

  • CFTR DNA mutatation analysis - confirms diagnosis if 2 CF-related mutations are found
    • F508 mutation accounts for 70% in Caucasians (30-48% in other groups), with 15-20 other common mutations accounting for 2-15%
    • Initial screen (e.g. Quest Diagnostics "CF screen") includes 23 (basic) to 32 (extended) of the most common CF mutations, and will detect CF in 90% of Caucasians and 97% of Ashkenazi Jews (lower in other ethnic groups)
    • If CF screen detects 0-1 mutations, consider expanded DNA analysis (e.g. Quest Diagnostics "CF Complete") via CFTR gene sequencing



Algorithm (Katkin)

CF_Algo_from_utd.gif


CF and ABPA