Diagnostic dilemmas resulting from the immunoreactive trypsinogen/DNA cystic fibrosis newborn screening algorithm

UMMS Affiliation

Department of Pediatrics; New England Newborn Screening Program

Publication Date


Document Type



*Algorithms; Chlorides; Clinical Protocols; Cystic Fibrosis; Cystic Fibrosis Transmembrane Conductance Regulator; DNA Mutational Analysis; Decision Trees; False Negative Reactions; False Positive Reactions; Follow-Up Studies; Humans; Immunoassay; Infant, Newborn; Massachusetts; Mutation; Neonatal Screening; Practice Guidelines as Topic; Sweat; Trypsinogen


Genetics and Genomics | Medical Genetics | Pediatrics


OBJECTIVE: To quantitate the proportion of infants identified through cystic fibrosis (CF) newborn screening (NBS) by an immunoreactive trypsinogen (IRT)/DNA screening algorithm who have an unclear diagnosis as defined by the findings of an elevated IRT level and either 1) 2 CF gene (CFTR) mutations detected and sweat chloride level <60 mEq/L; or 2) 0 or 1 CFTR mutations and a "borderline" sweat chloride level >or=30 and <60 mEq/L.

STUDY DESIGN: Using the 4-year cohort of CF-affected infants recently described by the Massachusetts CF NBS program, we identified and described the number of infants with the diagnostic characteristics (diagnostic dilemmas) aforementioned.

RESULTS: Of infants with positive results on CF NBS who had 1 CFTR mutation detected and a borderline sweat chloride concentration, nearly 20% displayed a second CFTR mutation on further evaluation. Of all infants with positive CF NBS results considered affected with CF, 11% had a diagnosis that fell into 1 of the diagnostic dilemma categories aforementioned.

CONCLUSIONS: Four problematic diagnostic categories generated by CF NBS are defined. In the absence of data on the natural history of such infants, careful follow-up is recommended for infants in whom a definitive diagnosis is elusive.

DOI of Published Version



J Pediatr. 2005 Sep;147(3 Suppl):S78-82. Link to article on publisher's site

Journal/Book/Conference Title

The Journal of pediatrics

Related Resources

Link to Article in PubMed

PubMed ID