In a child with respiratory distress, failure to thrive. His sweat chloride levels were estimated at 35 meq/L and 41 meq/L. What is next best test to do cystic fibrosis for diagnosis -
Ans-A i.e., the Transepithelial nasal potential difference Diagnosis of cystic fibrosis Sweat chloride testingThe sweat test is the standard approach to diagnosis.The diagnosis is made by elevated sodium and chloride level in the sweat > 60 meq/l.Two tests on different days are required for accurate diagnosis.A normal sweat chloride does not exclude the diagnosis.Genotyping and other tests such as measurement of nasal membrane potential difference, the pancreatic function should be done if there is high clinical suspicion of cystic fibrosis.Nasal potential differenceMeasurement of nasal transepithelial potential difference in vivo can be a 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 a loss of this potential difference.The 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.Genetic analysisCystic fibrosis is an autosomal recessive disorder.It is caused due to a defect in CFTR (Cystic fibrosis transmembrane conductance regulator) protein.Cystic fibrosis is associated with a large number of mutations.More than 1500 CFTR polymorphisms are associated with cystic fibrosis syndrome.The most prevalent mutation of CFTR is the deletion of a single phenylalanine residue at amino acid A508This mutation is responsible for high incidence of cystic fibrosis in northern European populations.Approximately 50% of individuals with CF who are of northern European ancestry are homozygous for A508 and > 70% carry at least one A508 gene. The remainder of patients has an extensive array of mutation, none of which has the prevalence of more than several percents.Testing for cystic fibrosis mutation was not possible because of the large no. of mutations associated with the disease.Now day's commercial laboratories test for 30-80 of the most common CFTR mutations.This testing identifies > 90% of individuals who carry 2 CF mutations.Nowhere it is mentioned in the texts that testing only for A508 is enough for diagnosis.Detection of at least 2 CF mutations is 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 differenceDemonstrating 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.
Nasal transmembrane potential difference
DNA analysis AF 508 mutation
CT chest
72-hour fecal fat estimation