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 language | English |
|---|---|
| Pages (from-to) | 212-215 |
| Number of pages | 4 |
| Journal | European Journal of Pediatrics |
| Volume | 161 |
| Issue number | 4 |
| DOIs | |
| Publication status | Published - 2002 |
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Keywords
- CFTR gene
- Cystic fibrosis
- Delayed diagnosis
- Sweat test
ASJC Scopus subject areas
- Pediatrics, Perinatology, and Child Health
Cite this
Negative sweat test in hypertrypsinaemic infants with cystic fibrosis carrying rare CFTR mutations. / Padoan, Rita; Bassotti, Alessandra; Seia, Manuela; Corbetta, Carlo.
In: European Journal of Pediatrics, Vol. 161, No. 4, 2002, p. 212-215.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Negative sweat test in hypertrypsinaemic infants with cystic fibrosis carrying rare CFTR mutations
AU - Padoan, Rita
AU - Bassotti, Alessandra
AU - Seia, Manuela
AU - Corbetta, Carlo
PY - 2002
Y1 - 2002
N2 - 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.
AB - 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.
KW - CFTR gene
KW - Cystic fibrosis
KW - Delayed diagnosis
KW - Sweat test
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U2 - 10.1007/s00431-001-0910-8
DO - 10.1007/s00431-001-0910-8
M3 - Article
VL - 161
SP - 212
EP - 215
JO - European Journal of Pediatrics
JF - European Journal of Pediatrics
SN - 0340-6199
IS - 4
ER -