Cystic fibrosis diagnosed by state newborn screening: Or is it?

Abstract

<jats:p> Newborn screening for cystic fibrosis is universal across the United States; however, each state chooses the method by which they screen. Illinois employs a two-step process which includes the measurement of the immunoreactive trypsinogen followed by an assay designed to detect 74 of the most common genetic mutations in the cystic fibrosis transmembrane conductance regulator protein. We report the case of an infant born in Illinois with a positive cystic fibrosis newborn screening with an elevated immunoreactive trypsinogen and two genetic mutations identified (F508del/F508del). The primary care physician informed the parents their child had cystic fibrosis and referred her for a confirmatory sweat test which was negative for cystic fibrosis. Upon further investigation, the assay was found to have been set up incorrectly and repeat analysis identified the genotype F508del/F508C. This case highlights the importance of performing the confirmatory sweat test prior to making a diagnosis of cystic fibrosis. </jats:p>

Soft, skin-interfaced sweat stickers for cystic fibrosis diagnosis and management

“…This typically involves measurement of immunoreactive trypsinogen (IRT), a pancreatic protein that is elevated in newborns with CF, followed by CFTR mutation testing in infants with elevated IRT (2,5,6). This test captures almost all infants with CF, but it suffers from several limitations including a high false-positive rate (2,13); an inability to ascertain rare CFTR mutations, deletions, and duplications (6); and, in the case of DNA-based mutation testing, poor sensitivity in detecting mutations in infants from ethnic and racial minority groups (14). These limitations necessitate the use of quantitative sweat testing to confirm a CF diagnosis even in cases where only one CFTR mutation is found (often indicating a heterozygote carrier); in some regions, a very high IRT concentration is considered a positive screening test.…”