Diagnostic Dilemmas Resulting From the Immunoreactive trypsinogen/DNA Cystic Fibrosis Newborn Screening Algorithm

J Pediatr. 2005 Sep;147(3 Suppl):S78-82. doi: 10.1016/j.jpeds.2005.08.017.


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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Validation Study

MeSH terms

  • Algorithms*
  • Chlorides / analysis
  • Clinical Protocols
  • Cystic Fibrosis / blood
  • Cystic Fibrosis / diagnosis*
  • Cystic Fibrosis / genetics
  • Cystic Fibrosis Transmembrane Conductance Regulator / genetics
  • DNA Mutational Analysis / methods*
  • DNA Mutational Analysis / standards
  • Decision Trees
  • False Negative Reactions
  • False Positive Reactions
  • Follow-Up Studies
  • Humans
  • Immunoassay / methods*
  • Immunoassay / standards
  • Infant, Newborn
  • Massachusetts
  • Mutation / genetics
  • Neonatal Screening / methods*
  • Neonatal Screening / standards
  • Practice Guidelines as Topic
  • Sweat / chemistry
  • Trypsinogen / blood*


  • CFTR protein, human
  • Chlorides
  • Cystic Fibrosis Transmembrane Conductance Regulator
  • Trypsinogen