WS11.6 Interpretation of nasal potential difference (nPD) measurements in difficult cases of possible cystic fibrosis and the role of published equations

Abstract

Objectives: Norway introduced newborn screening for Cystic Fibrosis (CF) in March 2012 based on a three tier immunoreactive trypsinogen (IRT)/DNA/DNA protocol. The cystic fibrosis transmembrane conductance regulator (CFTR) mutation spectrum of Norwegian CF patients as well as mutations previously not seen in the population were included in the mutation panels. We present the results from the first 22 months of nationwide CF screening in Norway. Methods: IRT was measured using GSPTM (Perkin Elmer) and samples above 60 ng/ml were included in 2nd tier testing. This involved Luminex-based analysis of 71 mutations and Sanger sequencing of a local common mutation. If only one mutation was found, 3rd tier testing included sequencing of an additional panel of clinically rare alleles found in Norwegian CF patients. Infants carrying two mutations were reported for diagnostic follow-up. Results: At the end of 2013, 111 648 samples had been screened for CF and 875 children (0.78%) had tested positive in primary IRT screening. 2nd tier DNA assessments revealed 22 samples carrying two CFTR mutations. 3rd tier DNA testing of 86 samples disclosed one child with two mutations. Based on the 23 reported children the most frequent alleles were p.R117H (32.6%) and p.F508del (30.4%). In addition, five infants where no mutation was found were reported due to very high IRT values (>400 ng/ml). Conclusion: We found fewer children with a clear CF genotype than expected, and the CFTR mutations and allele frequencies were different compared to clinical material. This suggests reviewing the IRT cut-off level and continued reporting of p.R117H variants as well as extending the 2nd tier mutation panel. WS11.6 Interpretation of nasal potential difference (nPD) measurements in difficult cases of possible cystic fibrosis and the role of published equations R. Pabary1,2, M. Waller2, K. Harman2, I. Ya-Tung2, D. Bilton2,3, N.J. Simmonds2,3, E.W. Alton2, J.C. Davies1,2. 1Royal Brompton & Harefield NHS Foundation Trust, Paediatric Respiratory Medicine, London, United Kingdom; 2Imperial College, National Heart and Lung Institute, London, United Kingdom; 3Royal Brompton & Harefield NHS Foundation Trust, Adult Cystic Fibrosis Unit, London, United Kingdom