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

Rita Padoan, Alessandra Bassotti, Manuela Seia, Carlo Corbetta

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish
Pages (from-to)212-215
Number of pages4
JournalEuropean Journal of Pediatrics
Volume161
Issue number4
DOIs
Publication statusPublished - 2002

Keywords

  • CFTR gene
  • Cystic fibrosis
  • Delayed diagnosis
  • Sweat test

ASJC Scopus subject areas

  • Pediatrics, Perinatology, and Child Health

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