<prompt> In a child with respiratory distress, failure to thrive. His sweat chloride levels were estimated 35 mEqLand 41 mEqL. What is next best test to do cystic fibrosis for diagnosis?Transepithelial nasal potential differenceDNA analysis F 508 mutationCT chest72-hour fecal fat estimation  <response>: Ans. a. Transepithelial nasal potential difference Ref: Nelson 18e 1804, 1803Nasal potential difference is a sensitive test of electrolyte transport CFTR function that can be used to support or refute a diagnosis of cystic fibrosis.Diagnosis of cystic fibrosisSweat chloride testingNasal potential differenceGenetic analysis The sweat test is the standard approach to diagnosis. The diagnosis is made by elevated sodium and chloride level in the sweat 60 mEql. Two tests on different days are required for accurate diagnosis. A normal sweat chloride dose not exclude the diagnosis. Genotyping and other tests such as measurement of nasal membrane potential difference, pancreatic function should be done if there is high clinical suspicion of cystic fibrosis. Measurement of nasal transepithelial potential difference in vivo can be useful adjunct in the diagnosis of cystic fibrosis. Individual with cystic fibrosis demonstrate a significantly more negative baseline nasal potential difference, with the topical application of amiloride there is loss of this potential difference.Nasal potential difference is a sensitive test of electrolyte transport CFTR function that can be used to support or refute a diagnosis of cystic fibrosis. It is caused due to defect in CFTR Cystic fibrosis transmembrane conductance regulator protein. Cystic fibrosis is associated with large number of mutations. More than 1500 CFTR polymorphisms are associate with cystic fibrosis syndrome. The most prevalent mutation of CFTR is the deletion of single phenylalanine residue at amino acid D508This mutation is responsibly for high incidence of cystic fibrosis in northern European populations. Now days commercial laboratories test for 30- 80 of the most common CFTR mutations. Detection of atleast 2 CF mutations are necessary for making the diagnosis of cystic fibrosis. Diagnostic Criteria for Cystic FibrosisPresence of typical clinical featuresrespiratory, gastrointestinal or genitourinaryorA history of CF in a siblingorA positive newborn screening testplusLaboratory evidence for CFTR dysfunctionTwo eleveated sweat chloride concentrations obtained on separate daysorIdentification of two CF mutationsorAn abnormal nasal potential difference. 