Is There an Acquired Form of Cystic Fibrosis?
No, cystic fibrosis cannot be acquired—it is exclusively an autosomal recessive genetic disorder caused by mutations in both copies of the CFTR gene present from birth. 1
Why CF Cannot Be Acquired
- CF is a genetic disease requiring biallelic CFTR mutations (mutations on both maternal and paternal chromosomes) that must be inherited at conception 1
- The CFTR gene on chromosome 7q31.2 encodes a chloride channel protein essential for normal epithelial cell function 1
- Over 1,950 CFTR mutations have been identified, with the F508del mutation accounting for 66-70% of CF alleles worldwide 1, 2
- Birth prevalence is approximately 1/3,700 in the United States, with higher rates (1/2,500-3,500) among non-Hispanic whites 1
Conditions That Mimic CF Symptoms
While CF itself cannot be acquired, several conditions can produce strikingly similar respiratory and pancreatic manifestations:
Atypical CF and CFTR-Related Disorders
- "Mild" CFTR mutations can produce monosymptomatic or late-onset disease that mimics acquired conditions 3, 4
- Patients with compound heterozygous mutations (one severe mutation like F508del paired with a mild mutation like 5T polymorphism) may have minimal or no symptoms until adulthood 1
- These individuals can present with isolated bronchiectasis, chronic sinusitis, or recurrent pancreatitis without classic CF features 4
Specific CFTR-Related Phenotypes That Appear "Acquired":
Congenital Bilateral Absence of Vas Deferens (CBAVD)
- 78% of men with CBAVD have at least one CFTR mutation, with 46% having two identifiable mutations 1
- These men typically have normal pulmonary and pancreatic function, presenting only with male infertility 1
- The most common pairing is F508del with the 5T polymorphism (17% of CBAVD cases) 1
Late-Onset Pulmonary Disease
- Patients with residual CFTR function can develop bronchiectasis and chronic bacterial infections in adulthood without prior CF diagnosis 4
- These individuals may have been asymptomatic in childhood and appear to have "acquired" lung disease 3
Idiopathic Chronic Pancreatitis
- CFTR mutations are associated with recurrent pancreatitis in adults without other CF manifestations 4
- Patients maintain pancreatic sufficiency but experience episodic inflammation 4
Non-CF Conditions With Similar Presentations:
Primary Ciliary Dyskinesia
- Produces chronic sinopulmonary disease with bronchiectasis similar to CF
- Distinguished by absent or dysfunctional cilia rather than CFTR defects
- Does not cause pancreatic insufficiency or elevated sweat chloride
Chronic Pancreatitis (Non-CFTR)
- Alcohol-related, autoimmune, or hereditary pancreatitis can mimic CF pancreatic disease
- Lacks respiratory symptoms and normal sweat chloride testing
Non-CF Bronchiectasis
- Post-infectious, immunodeficiency-related, or idiopathic bronchiectasis produces similar respiratory symptoms
- Sweat chloride testing (>60 mEq/L) definitively distinguishes CF from other causes 1, 5
Critical Diagnostic Distinction
The sweat chloride test remains the gold standard for distinguishing CF from CF-mimicking conditions:
- Values >60 mEq/L confirm CF diagnosis 1, 5
- Values 30-59 mEq/L in infants may require repeat testing 6, 5
- Normal sweat chloride (<30 mEq/L) excludes classic CF but does not rule out CFTR-related disorders 1
Common Pitfall to Avoid
Do not assume adult-onset bronchiectasis or pancreatitis excludes CF—comprehensive CFTR genetic testing should be performed in patients with unexplained chronic sinopulmonary disease, bronchiectasis, or recurrent pancreatitis, as mild CFTR mutations can produce late-presenting phenotypes that appear "acquired" 3, 4, 7. The phenotypic spectrum extends far beyond classic childhood CF, and approximately 5% of the general population carries the 5T polymorphism that can act as a disease-causing mutation when paired with a severe CFTR mutation 1.