Combining Immunoreactive Trypsinogen and Pancreatitis-Associated Protein Assays, a Method of Newborn Screening for Cystic Fibrosis that Avoids DNA Analysis

2005 ◽  
Vol 147 (3) ◽  
pp. 302-305 ◽  
Author(s):  
Jacques Sarles ◽  
Patrice Berthézène ◽  
Christian Le Louarn ◽  
Claude Somma ◽  
Jean-Marc Perini ◽  
...  
Keyword(s):  
Cystic Fibrosis ◽  
Newborn Screening ◽  
Dna Analysis ◽  
Protein Assays ◽  
Pancreatitis Associated Protein ◽  
Immunoreactive Trypsinogen

scholarly journals A product of immunoreactive trypsinogen and pancreatitis-associated protein as second-tier strategy in cystic fibrosis newborn screening

2016 ◽  
Vol 15 (6) ◽  
pp. 752-758 ◽  
Author(s):  
Sophia Weidler ◽  
Konrad H. Stopsack ◽  
Jutta Hammermann ◽  
Olaf Sommerburg ◽  
Marcus A. Mall ◽  
...  
Keyword(s):  
Cystic Fibrosis ◽  
Newborn Screening ◽  
Second Tier ◽  
Pancreatitis Associated Protein ◽  
Immunoreactive Trypsinogen

scholarly journals Cystic Fibrosis Newborn Screening in Austria Using PAP and the Numeric Product of PAP and IRT Concentrations as Second-Tier Parameters

Diagnostics ◽  
2021 ◽  
Vol 11 (2) ◽  
pp. 299
Author(s):  
Maximilian Zeyda ◽  
Andrea Schanzer ◽  
Pavel Basek ◽  
Vera Bauer ◽  
Ernst Eber ◽  
...  
Keyword(s):  
Cystic Fibrosis ◽  
Newborn Screening ◽  
Dried Blood Spots ◽  
False Negatives ◽  
Blood Spots ◽  
Second Tier ◽  
Pancreatitis Associated Protein ◽  
Immunoreactive Trypsinogen ◽  
Sweat Tests ◽  
Observation Period

In Austria, newborns have been screened for cystic fibrosis (CF) by analyzing immunoreactive trypsinogen (IRT) from dried blood spots (DBS)s for nearly 20 years. Recently, pancreatitis-associated protein (PAP) analysis was introduced as a second-tier test with the aim of reducing recalls for second DBS cards while keeping sensitivity high. For 28 months, when IRT was elevated (65–130 ng/mL), PAP was measured from the first DBS (n = 198,927) with a two-step cut-off applied. For the last 12 months of the observation period (n = 85,421), an additional IRT×PAP cut-off was introduced. If PAP or IRT×PAP were above cut-off, a second card was analyzed for IRT and in case of elevated values identified as screen-positive. Above 130 ng/mL IRT in the first DBS, newborns were classified as screen-positive. IRT analysis of first DBS resulted in 1961 (1%) tests for PAP. In the first 16 months, 26 of 93 screen-positive were confirmed to have CF. Two false-negatives have been reported (sensitivity = 92.8%). Importantly, less than 30% of families compared to the previous IRT-IRT screening scheme had to be contacted causing distress. Adding IRT×PAP caused a marginally increased number of second cards and sweat tests to be requested during this period (15 and 3, respectively) compared to the initial IRT-PAP scheme. One case of confirmed CF was found due to IRT×PAP, demonstrating an increase in sensitivity. Thus, the relatively simple and economical algorithm presented here performs effectively and may be a useful model for inclusion of CF into NBS panels or modification of existing schemes.

P015 Evaluation of the specificity and sensitivity of the cut-off values of immunoreactive trypsinogen in the cystic fibrosis newborn screening program

2021 ◽  
Vol 20 ◽  
pp. S43
Author(s):  
T. Ramasli Gursoy ◽  
P. Asfuroglu ◽  
T. Sismanlar Eyuboglu ◽  
A.T. Aslan ◽  
A.I. Yilmaz ◽  
...  
Keyword(s):  
Cystic Fibrosis ◽  
Newborn Screening ◽  
Screening Program ◽  
Newborn Screening Program ◽  
Specificity And Sensitivity ◽  
Immunoreactive Trypsinogen

Newborn Screening for Cystic Fibrosis

PEDIATRICS ◽  
1991 ◽  
Vol 87 (6) ◽  
pp. 954-955
Author(s):  
IAN C. T. LYON ◽  
DIANNE R. WEBSTER
Keyword(s):  
Cystic Fibrosis ◽  
Newborn Screening ◽  
Elevated Level ◽  
Meconium Ileus ◽  
Screening Tests ◽  
Initial Screening ◽  
False Negatives ◽  
Immunoreactive Trypsinogen

To the Editor.— The report on newborn screening for cystic fibrosis1 illustrates the need for continued evaluation of such programs. The authors state that the identification of cases of cystic fibrosis (CF) by an elevated level of immunoreactive trypsinogen (IRT) in second (follow-up) samples from infants with positive initial screening tests could result in false negatives in 27% of cases of cystic fibrosis without meconium ileus (MI). We have screened 401 122 infants using the method originally reported.2

Clarification of Laboratory and Clinical Variables That Influence Cystic Fibrosis Newborn Screening With Initial Analysis of Immunoreactive Trypsinogen

PEDIATRICS ◽  
2009 ◽  
Author(s):  
M. Kloosterboer ◽  
G. Hoffman ◽  
M. Rock ◽  
W. Gershan ◽  
A. Laxova ◽  
...  
Keyword(s):  
Cystic Fibrosis ◽  
Newborn Screening ◽  
Clinical Variables ◽  
Initial Analysis ◽  
Immunoreactive Trypsinogen

scholarly journals The Role of Extended CFTR Gene Sequencing in Newborn Screening for Cystic Fibrosis

2020 ◽  
Vol 6 (1) ◽  
pp. 23 ◽  
Author(s):  
Anne Bergougnoux ◽  
Maureen Lopez ◽  
Emmanuelle Girodon
Keyword(s):  
Cystic Fibrosis ◽  
Newborn Screening ◽  
Dna Analysis ◽  
Genetic Diseases ◽  
Major Drawback ◽  
Coding Regions ◽  
Sequencing Technologies ◽  
Second Tier ◽  
Real Challenge

There has been considerable progress in the implementation of newborn screening (NBS) programs for cystic fibrosis (CF), with DNA analysis being part of an increasing number of strategies. Thanks to advances in genomic sequencing technologies, CFTR-extended genetic analysis (EGA) by sequencing its coding regions has become affordable and has already been included as part of a limited number of core NBS programs, to the benefit of admixed populations. Based on results analysis of existing programs, the values and challenges of EGA are reviewed in the perspective of its implementation on a larger scale. Sensitivity would be increased at best by using EGA as a second tier, but this could be at the expense of positive predictive value, which improves, however, if EGA is applied after testing a variant panel. The increased detection of babies with an inconclusive diagnosis has proved to be a major drawback in programs using EGA. The lack of knowledge on pathogenicity and penetrance associated with numerous variants hinders the introduction of EGA as a second tier, but EGA with filtering for all known CF variants with full penetrance could be a solution. The issue of incomplete knowledge is a real challenge in terms of the implemention of NBS extended to many genetic diseases.

scholarly journals Newborn Screening for Cystic Fibrosis by Use of a Multiplex Immunoassay

2010 ◽  
Vol 56 (3) ◽  
pp. 445-450 ◽  
Author(s):  
Barbara A Lindau-Shepard ◽  
Kenneth A Pass
Keyword(s):  
Cystic Fibrosis ◽  
Newborn Screening ◽  
Screening Program ◽  
Pancreatic Disease ◽  
High Rate ◽  
Dna Testing ◽  
Second Tier ◽  
Sample Set ◽  
Positive Results ◽  
Immunoreactive Trypsinogen

Abstract Background: Since its beginnings, newborn screening for cystic fibrosis (CF) using an assay for immunoreactive trypsinogen (IRT) has been plagued by a high rate of false-positive results (screen positive, diagnosis negative), despite attempts to reduce this rate by use of altered cutoffs and second-tier DNA testing. IRT exists as 2 isoforms: IRT1 and IRT2, with IRT2 being more closely aligned with pancreatic disease, including CF. Assay standardization between programs is a continuing problem because the IRT assays currently in use variously recognize either 1 or both isoforms. Here we report the development of a multiplexed assay for both forms of IRT simultaneously. Methods: Using 2 different Luminex bead sets, we developed assays for each IRT isoform separately and then combined them. Using the sum of IRT1 and IRT2 values (IRT1+IRT2), we compared the results with a CF kit currently in use. Results: In a sample set consisting of 16 cases confirmed positive for CF, we established a cutoff at >97 μg/L total IRT. Seven of 8 carriers with 1 CF mutation screen-positive by the standard method were also screen-positive by IRT1+IRT2. Of 32 cases screen-positive by standard IRT, 11 were screen-negative by IRT1+IRT2. None of these 11 cases had CF mutations identified by the screening program. Conclusions: These data indicate that the multiplex method with specificity for 2 isoforms of IRT has performance comparable to that of a standard IRT method and the advantage of improved standardization by detection of the 2 isoforms.

Cystic fibrosis newborn screening: outcome of infants with normal sweat tests

2017 ◽  
Vol 103 (8) ◽  
pp. 753-756 ◽  
Author(s):  
Claire Edmondson ◽  
Christopher Grime ◽  
Ammani Prasad ◽  
Jacqui Cowlard ◽  
Chinedu E C Nwokoro ◽  
...  
Keyword(s):  
Cystic Fibrosis ◽  
Newborn Screening ◽  
Genome Sequencing ◽  
Dna Analysis ◽  
Gene Mutations ◽  
High Serum ◽  
Sweat Test ◽  
Sweat Chloride ◽  
South East England

Newborn babies positively screened for cystic fibrosis (CF) (high serum immunoreactive trypsin (IRT) with DNA analysis) are referred for a diagnostic sweat test, which may be normal (sweat chloride <30 mmol/L). Unless two gene mutations are identified during Newborn screening (NBS), the babies are discharged from follow-up. We wished to check that none had subsequently developed symptoms suggestive of CF. We retrospectively reviewed patient notes and contacted general practitioners of all babies with a negative sweat test, conducted in one of the four paediatric specialist CF centres in London, over the first 6 years of screening in South East England.Of 511 babies referred, 95 (19%) had a normal sweat test. Five (5%) had CF diagnosed genetically, two of them on extended genome sequencing after clinical suspicion. Eleven (12%) were designated as CF screen positive inconclusive diagnosis (CFSPID); one of the five CF children was originally designated as CFSPID. Seventy-nine (83%) were assumed to be false-positive cases and discharged; follow-up data were available for 51/79 (65%); 32/51 (63%) had no health issues, 19/51 (37%) had other significant non-CF pathology.These results are reassuring in that within the limitations of those lost to follow-up, CF symptoms have not emerged in the discharged children. The high non-CF morbidity in these children may relate to known causes of high IRT at birth. Clinicians need to be aware that a child can have CF despite a normal sweat test following NBS, and if symptoms suggest the diagnosis, further testing, including extended genome sequencing, is required.

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