Negative sweat test in hypertrypsinaemic infants with cystic fibrosis carrying rare CFTR mutations

Eur J Pediatr. 2002 Apr;161(4):212-5. doi: 10.1007/s00431-001-0910-8.


Persistent hypertrypsinaemia in newborn screening for cystic fibrosis (CF) recognises subjects at high risk to be affected. Diagnosis is confirmed by a positive sweat test and/or by the presence of two mutations in the cystic fibrosis transmembrane regulator gene. The aim of the present study was to evaluate the occurrence of a negative sweat test (chloride < 60 mmol/l) during the first months of life, in hypertrypsinaemic infants, which would lead to a delayed diagnosis. We reviewed clinical charts of CF patients born between January 1993 and September 1998, when the neonatal screening programme consisted of an immunoreactive trypsinogen (IRT)/DNA (F508del) + IRT strategy. Laboratory and clinical data were collected for patients diagnosed after 12 months of life. Out of 446,492 newborns, 104 CF patients were diagnosed giving an overall incidence of 1:4293. Of these, six had a blood IRT level above the cut off value (99th percentile) and a negative sweat test in the first trimester of life. At a mean age of 3.5years, the patients were again referred to our CF Centre for re-evaluation in order to confirm or exclude the disorder. Molecular analysis identified the following genotypes: F508del/A309D, F508del/3849 + 10kbC-->T, F508del/R117H (in two patients), R117H/ L997F, and F508del/R117L.

Conclusion: Infants with cystic fibrosis bearing a spectrum of mild cystic fibrosis transmembrane regulator gene mutations may present as hypertrypsinaemic newborns with a sweat chloride within the normal range. Reference values for normal sweat test during the first months of life should be revised. A wide molecular genetic analysis is recommended for newborns presenting persistent hypertrypsinaemia and a sweat test result > 30 mmol/l in order to diagnose atypical forms of the disease.

MeSH terms

  • Child
  • Child, Preschool
  • Chlorides / analysis
  • Cystic Fibrosis / blood
  • Cystic Fibrosis / diagnosis*
  • Cystic Fibrosis / genetics
  • Cystic Fibrosis Transmembrane Conductance Regulator / analysis*
  • Cystic Fibrosis Transmembrane Conductance Regulator / genetics
  • Female
  • Humans
  • Infant
  • Infant, Newborn
  • Male
  • Mutation
  • Neonatal Screening*
  • Sweat / chemistry*
  • Trypsin / blood
  • Trypsinogen / blood


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