Neonatal screening for cystic fibrosis using immunoreactive trypsinogen and direct gene analysis: four years' experience

Ranieri, Enzo; Lewis, Barry; Gerace, R L; Ryall, Rosemary L.; Morris, C. Phillip; Pv, Nelson; Carey, W.F.; Robertson, Evelyn F.

doi:10.1136/bmj.308.6942.1469

Cited by 80 publications

(40 citation statements)

References 25 publications

(5 reference statements)

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“…This is consistent with the higher immunoreactive trypsin concentrations found in~F508 heterozygotes at 4-6 days of age" and the increased frequency noted by Laroche and Traverr" and Lucotte and coworkers," and found by other programmes using the immunoreactive trypsin-DNA protocol.' [13][14][15][16][17] In the present study babies without cystic fibrosis who were hypertrypsinaemic at 6 days and heterozygous for~F508 also had, on average, higher immunoreactive trypsin concentrations in the 27 day blood sample than those without the mutation (table 1).…”

Section: Resultsmentioning

confidence: 86%

“…Babies without F508 are reported as normal, though some will have the disease. This immunoreactive trypsin-DNA two-stage screen, instituted by Ranieri er azt' 14 and now reported in other programmes,' [15][16][17][18] has the advantages of an earlier diagnosis in patients homozygous for F508 and of eliminating the need for a second blood sample. However, the increase in the number of unaffected babies given a sweat test seems to us to be a significant drawback of this approach.…”

Section: Subjects-437859 Babies Born Between August 1989 and March 1996mentioning

confidence: 99%

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Neonatal Screening for Cystic Fibrosis in the Trent Region (UK): Two-Stage Immunoreactive Trypsin Screening Compared with a Three-Stage Protocol with DNA Analysis as an Intermediate Step

Pollitt

Dalton²,

Evans³

et al. 1997

J Med Screen

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Objectives— To assess neonatal screening for cystic fibrosis using immunoreactive trypsin, either alone or in conjunction with DNA analysis for the AF508 mutation. A novel three-stage screening protocol was compared with the previously introduced two-stage immunoreactive trypsin-DNA protocol. Design— (a) Collection of data from a 41/2 year period (phase 1) of two-stage immunoreactive trypsin screening. The initial dried blood samples were obtained at 6 days of age and repeat samples at 27 days of age from babies with results above the 99.5th centile. Babies with persistent hypertrypsinaemia were referred for a diagnostic sweat test. (b) Retrospective DNA analysis: Patients with cystic fibrosis diagnosed in phase 1 were genotyped and most samples from babies with increased initial immunoreactive trypsin but normal results in the second sample were analysed for the δF508 mutation, (c) Phase 2, a prospective study of a three-stage neonatal screening protocol, in which only babies heterozygous for the δF508 cystic fibrosis mutation progressed to the second immunoreactive trypsin test. Setting— The Trent neonatal screening programme. Subjects— 437 859 babies born between August 1989 and March 1996. Main outcome measures— Proportions of unaffected babies requiring a second blood sample or a sweat test. Overall sensitivity for the detection of cystic fibrosis. Results— The two-stage screen failed to identify six out of 94 cases of cystic fibrosis (without meconium ileus). The introduction of the DNA analysis step would have resulted in one additional case being missed. With the three-stage screen there was a 92% reduction in babies requiring a second blood sample and an 80% reduction in negative sweat tests, results close to the predictions of the retrospective study. Conclusions— The three-stage screening protocol is a marked improvement on the two-stage immunoreactive trypsin strategy and on the two-stage immunoreactive trypsin-DNA strategy recently introduced in some other screening programmes.

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Section: Resultsmentioning

confidence: 86%

Section: Subjects-437859 Babies Born Between August 1989 and March 1996mentioning

confidence: 99%

Neonatal Screening for Cystic Fibrosis in the Trent Region (UK): Two-Stage Immunoreactive Trypsin Screening Compared with a Three-Stage Protocol with DNA Analysis as an Intermediate Step

Pollitt

Dalton²,

Evans³

et al. 1997

J Med Screen

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“…All centres that screen currently use neonatal immunoreactive trypsinogen (IRT) as the primary screen followed by DF508 mutation analysis in those with an elevated (w99th percentile) IRT. One Australian centre (South Australia) includes the mutations G551D, G452X, DI507, R553X and R117H as part of routine screening of infants with an elevated IRT [12]. All individuals with a positive result on newborn screen (either one or two mutations) are referred for sweat testing.…”

Section: Methodsmentioning

confidence: 99%

Intron-8 polythymidine sequence in Australasian individuals with CF mutations R117H and R117C

Massie¹,

Poplawski²,

Wilcken³

et al. 2001

Eur Respir J

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Compound heterozygotes for a severe cystic fibrosis transmembrane conductance regulator (CFTR) mutation and the R117H or R117C mutation (R117H/ C) have clinical presentations that vary from classic cystic fibrosis (CF) to an incidental genetic finding.The aim of this study was to assess the influence of the intron-8 polythymidine sequence (IVS8) on the relationship between genotype and phenotype of individuals with R117H/C.All individuals with R117H/C known to CF clinics in Australia and New Zealand were retrospectively studied by collecting information on genotype, age, pancreatic status, sweat electrolytes, sputum microbiology and pulmonary function.Forty-one individuals (39 with R117H and two with R117C), 16 on an IVS8-5T background and 25 on an IVS8-7T background were identified. Twelve individuals presented clinically, four were siblings of known R117H/C compound heterozygotes and 25 were detected by newborn screening. Eleven of 14 of the IVS8-5T group (78%) with sweat chloride results available had sweat Clw60 mmol?L -1 compared to 5 (20%) of the R117H/7T group (Chi-squared~10.4, p~0.001). Two were pancreatic insufficient, both IVS8-5T. Two IVS8-5T individuals have recently died (aged 43 and 19) and of the 14 surviving IVS8-5T group, 11 (79%) are symptomatic compared to eight (32%) of the IVS8-7T individuals (Chi-squared~6.1, p~0.01).In conclusion, most individuals with R117H/C on a IVS8-5T background have an elevated sweat chloride and clinical cystic fibrosis, which in some cases is severe. Most individuals with R117H/C on an IVS8-7T background do not have clinical cystic fibrosis but should be followed for the development of clinical disease.

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“…In addition, immediate genetic confirmation of steroid CYP21 deficiency allows early treatment, which eliminates the risk of the salt-wasting syndrome. A two-tier strategy combining an immunologic technique with genetic confirmation has already been successfully introduced for neonatal screening for cystic fibrosis (17 ). In the majority of the screening programs, the nonspecificity of the 17-OHP assay accounts for Ͼ80% of all recalls.…”

Section: Clinical Chemistry 51 No 2 2005mentioning

confidence: 99%

Rapid Second-Tier Molecular Genetic Analysis for Congenital Adrenal Hyperplasia Attributable to Steroid 21-Hydroxylase Deficiency

Kösel¹,

Burggraf²,

Fingerhut³

et al. 2005

Clinical Chemistry

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Neonatal screening for cystic fibrosis using immunoreactive trypsinogen and direct gene analysis: four years' experience

Abstract: This strategy results in early and accurate diagnosis of cystic fibrosis and performs better than screening strategies based on immunoreactive trypsinogen measurement alone.

Cited by 80 publications

References 25 publications

Neonatal Screening for Cystic Fibrosis in the Trent Region (UK): Two-Stage Immunoreactive Trypsin Screening Compared with a Three-Stage Protocol with DNA Analysis as an Intermediate Step

Neonatal Screening for Cystic Fibrosis in the Trent Region (UK): Two-Stage Immunoreactive Trypsin Screening Compared with a Three-Stage Protocol with DNA Analysis as an Intermediate Step

Intron-8 polythymidine sequence in Australasian individuals with CF mutations R117H and R117C

Rapid Second-Tier Molecular Genetic Analysis for Congenital Adrenal Hyperplasia Attributable to Steroid 21-Hydroxylase Deficiency

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