Early detection of cystic fibrosis in newborns using radioimmunoanalysis of trypsin in drops of blood absorbed on filter paper. Final report for the period 1 July 1996 - 30 June 1997

The objective was to establish the cut-off value for blood immunoreactive trypsin radioimmunoassay used in the screening program for cystic fibrosis. Ten thousand capillary blood samples were collected from newborns 48 hours after birth on Schleider and Schnell No.903 filter paper and screened for immunoreactive trypsin (IRT) using polyethylene glycol assisted double antibody radioimmunoassay. Samples with IRT values greater then 800 ng/ml were subjected to further molecular biological diagnosis by amplification of exons 10 and 11 of CFTR gene. The products were analysed for ΔF508 and G542X mutations by hybridization with specific allele probe and G551D and R553X mutations by restriction enzyme digestion and Southern Blot. One hundred and forty one patients showed IRT values of greater then 800 ng/ml. Five of them were homozygotes for mutation at and ΔF508 and one was heterozygote the disease (one allele was positive for ΔF508 and the other allele for G542X). Only one of them presented with meconium ileus and the rest were asymptomatic. None of them has value less than 1200ng/ml in the first week of life. Five heterozygote for mutation at ΔF508 was also detected using 800ng/ml as cut-off. Based on the above findings, the cut-off value is established at 1200ng/ml. This gives specificity and sensitivity of 100%. (author)