Which test is considered definitive for the diagnosis of cystic fibrosis?

Which test is considered definitive for the diagnosis of cystic fibrosis?

• A. Chest X-ray
• B. Sweat chloride > 60 mmol/L on 2 occasions after pilocarpine
• C. DNA analysis
• D. PFTs

Answer: (C)

Cystic fibrosis is diagnosed definitively when genetic testing shows two disease-causing mutations in the CFTR gene, one on each chromosome. This direct demonstration of the underlying defect proves CF regardless of how the disease presents clinically or what a sweat test shows. Sweat chloride testing after pilocarpine is highly suggestive and remains an important supportive tool, but it can be influenced by age, technique, or atypical mutations, so it isn’t absolutely definitive on its own. If two clearly pathogenic CFTR mutations are found, the diagnosis is confirmed. If only one mutation is detected or results are inconclusive, further genetic testing or extended sequencing may be needed, guided by the clinical picture and sweat test findings.

Cystic fibrosis is diagnosed definitively when genetic testing shows two disease-causing mutations in the CFTR gene, one on each chromosome. This direct demonstration of the underlying defect proves CF regardless of how the disease presents clinically or what a sweat test shows. Sweat chloride testing after pilocarpine is highly suggestive and remains an important supportive tool, but it can be influenced by age, technique, or atypical mutations, so it isn’t absolutely definitive on its own. If two clearly pathogenic CFTR mutations are found, the diagnosis is confirmed. If only one mutation is detected or results are inconclusive, further genetic testing or extended sequencing may be needed, guided by the clinical picture and sweat test findings.