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In a child with respiratory distress, failure to thrive. His sweat chloride leveles were estimated 35 meq/L and 41 meq/L. What is next best test to do cystic fibrosis for diagnosis aEUR'
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The correct answer is  Trans epithelial nasal potential difference Diagnosis of cystic fibrosis Sweat chloride testing The sweat test is the standard approach to diagnosis. The diagnosis is made by elevated sodium and chloride level in the sweat > 60 meoll. 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. Nasal potential difference Measurement of nasal transepithelial potential difference in vivo can be useful adjunct in the diagnosis of cystic fibrosis. Individuals 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 transpo (CFTR) function that can be used to suppo or refute a diagnosis of cystic fibrosis. Genetic analysis Cystic .fibrosis is an autosomal recessive disorder. 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 polymoiphisms are associated with cystic fibrosis syndrome. The most prevalent mutation of CFTR is the deletion of single phenylalanine residue at amino acid 4.508 This mutation is responsible for high incidence of cystic fibrosis in nohern European populations. Approximately 50% of individuals with CF who are of nohern European ancestry are homozygous for 4.508 and > 70% carry at least one 4.508 gene. The remainder of patients has an extensive array of mutation, none of which has prevalence of more than several percent. Testing for cystic .fibrosis mutation was not possible because of the large no. of mutations associated with the disease. Now days commercial laboratories test for 30-80 of the most common CFTR mutations. This testing identifies > 90% individuals who carry 2 CF mutations. No where it is mentioned in the texts that testing only for 4508 is enough for diagnosis. Detection of atleast 2 CF mutations are necessary for making the diagnosis of cystic fibrosis. The patient has features of cystic fibrosis but sweat chloride levels are normal. - To diagnose cystic .fibrosis in this patient, another laboratory evidence demonstrating CFTR dysfunction is required. This can be done by two methods:? - Demonstrating abnormal potential difference - Demonstrating abnormal CF mutations. But the diagnostic criteria for cystic fibrosis requires. - Demonstration of two CF mutations (demonstration of single abnormal F508 mutation is not enough) So we are left with abnormal nasal potential difference. - It is an established laboratory evidence for CFTR dysfunction and is accepted as a diagnostic criteria to establish the diagnosis of cystic fibrosis. Diagnostic criteria for cystic fibrosis Presence of typical clinical features (respiratory, G.LT, genitourinary) OR A history of CF in a sibling OR A positive newborn screening test PLUS Laboratory evidence for CFTR Dysfunction Two elevated sweat chloride concentrations obtained on separate days OR Identification of two CF mutations OR An abnormal nasal potential difference