DELAYED DIAGNOSIS OF CYSTIC-FIBROSIS IN CHILDREN WITH A RARE GENOTYPE(DELTA-F508 R117H)/

Objective: In neonatal screening for cystic fibrosis (CF), infants rec ognised as Delta F508 heterozygotes require a sweat test to confirm th e diagnosis. However, compound heterozygotes with Delta F508 and the R 117H mutation are known to have nondiagnostic sweat chlorides (< 60 mm ol / L) at an early age. As genotyping for rare mutations is not readi ly available in Australia, there is a need to determine whether quanti tative pancreatic stimulation tests could facilitate the diagnosis of CF in three infants with the Delta F508/R117H mutation. Methodology: F ormal sweat testing, genotyping and pancreatic stimulation tests were performed in three subjects heterozygous for Delta F508 who initially had non-diagnostic sweat chloride results (40-60 mmol/L) but presented later with persisting chest symptoms and/or signs consistent with CF. Results: All three patients were shown to have the Delta F508/R117H g enotype with initial sweat chloride results ranging from 40 to 58 mmol /L Pancreatic stimulation tests demonstrated reduced enzyme secretion in two and decreased fluid, bicarbonate and chloride secretion in all three patients. Conclusions: in infants recognized as Delta F508 heter ozygotes by the newborn screening programme, the presence of an equivo cal sweat chloride does not exclude the diagnosis of GF. If such patie nts with an initially equivocal sweat chloride subsequently develop sy mptoms suggestive of CF and have a persisting non-diagnostic sweat chl oride then the diagnosis of CF can be confirmed by more extensive geno typing if available or by pancreatic stimulation testing.