Delayed diagnosis of cystic fibrosis in children with a rare genotype (delta F508/R117H)

Abstract

Objective: In neonatal screening for cystic fibrosis (CF), infants recognised as delta F508 heterozygotes require a sweat test to confirm the diagnosis. However, compound heterozygotes with delta F508 and the R117H mutation are known to have non-diagnostic sweat chlorides (< 60 mmol/L) at an early age. As genotyping for rare mutations is not readily available in Australia, there is a need to determine whether quantitative pancreatic stimulation tests could facilitate the diagnosis of CF in three infants with the delta F508/R117H mutation.

Methodology: Formal 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 genotype 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 heterozygotes by the newborn screening programme, the presence of an equivocal sweat chloride does not exclude the diagnosis of CF. If such patients with an initially equivocal sweat chloride subsequently develop symptoms suggestive of CF and have a persisting non-diagnostic sweat chloride then the diagnosis of CF can be confirmed by more extensive genotyping if available or by pancreatic stimulation testing.