Genetic and physiologic correlates of longitudinal immunoreactive trypsinogen decline in infants with cystic fibrosis identified through newborn screening

J Pediatr. 2006 Nov;149(5):650-657. doi: 10.1016/j.jpeds.2006.07.026.


Objectives: To characterize the time course and physiologic significance of decline in serum immunoreactive trypsinogen (IRT) levels in infants with cystic fibrosis (CF) by mode of diagnosis and genotype, and to examine IRT heritability.

Study design: We studied longitudinal IRT measurements in 317 children with CF. We developed statistical models to describe IRT decline. Pancreatic disease severity (Mild or Severe) was assigned using CF genotype and was confirmed in 47 infants through fat malabsorption studies.

Results: Infants with severe disease exhibited IRT decline with non-detectable levels typically seen by 5 years of age. Infants with mild disease exhibited a decline in the first 2 years, asymptomatically approaching a level greater than published norms. IRT and fecal fat were inversely correlated. IRT values in infants with meconium ileus (MI) were significantly lower than newborn-screened infants at birth. The high proportion of shared variation in predicted IRT values among sibling pairs with severe disease suggests that IRT is heritable.

Conclusions: IRT declines characteristically in infants with CF. Lower IRT values in newborns with MI suggest increased pancreatic injury. Furthermore, IRT is heritable among patients with severe disease suggesting genetic modifiers of early CF pancreatic injury. This study demonstrates heritability of a statistically modeled quantitative phenotype.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Biomarkers / analysis
  • Biomarkers / metabolism
  • Body Height
  • Body Weight
  • Chlorides / analysis
  • Cystic Fibrosis / enzymology
  • Cystic Fibrosis / genetics*
  • Cystic Fibrosis / immunology
  • Cystic Fibrosis / physiopathology*
  • DNA Mutational Analysis
  • Fats / analysis
  • Feces / chemistry
  • Female
  • Follow-Up Studies
  • Genetic Predisposition to Disease
  • Genotype
  • Humans
  • Ileus / genetics
  • Ileus / physiopathology
  • Infant, Newborn
  • Longitudinal Studies
  • Malabsorption Syndromes / genetics
  • Malabsorption Syndromes / physiopathology
  • Male
  • Neonatal Screening*
  • Predictive Value of Tests
  • Severity of Illness Index
  • Sweat / chemistry
  • Trypsinogen / blood*
  • Vitamins / blood


  • Biomarkers
  • Chlorides
  • Fats
  • Vitamins
  • Trypsinogen