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

1997 ◽  
Vol 4 (1) ◽  
pp. 23-28 ◽  
Author(s):  
R J Pollitt ◽  
A Dalton ◽  
S Evans ◽  
H N Hughes ◽  
D Curtis
Keyword(s):  
Cystic Fibrosis ◽  
Blood Sample ◽  
Neonatal Screening ◽  
Dna Analysis ◽  
Phase 1 ◽  
Sweat Test ◽  
Intermediate Step ◽  
Two Stage ◽  
Immunoreactive Trypsin ◽  
Screening Protocol

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.

Neonatal screening for cystic fibrosis, using immunoreactive trypsin assay in dried blood spots

1981 ◽  
Vol 113 (2) ◽  
pp. 111-121 ◽  
Author(s):  
Jeanette R. Crossley ◽  
Patricia A. Smith ◽  
Brian W. Edgar ◽  
Peter D. Gluckman ◽  
Robert B. Elliott
Keyword(s):  
Cystic Fibrosis ◽  
Neonatal Screening ◽  
Dried Blood Spots ◽  
Immunoreactive Trypsin ◽  
Blood Spots

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.

Chronic Sinusitis and a Negative Sweat Test in a Patient with Cystic Fibrosis

1995 ◽  
Vol 9 (4) ◽  
pp. 225-228 ◽  
Author(s):  
Todd T Kingdom ◽  
Kelvin C. Lee ◽  
Gerd J. Cropp
Keyword(s):  
Cystic Fibrosis ◽  
Unusual Case ◽  
Dna Analysis ◽  
Chronic Sinusitis ◽  
Carrier State ◽  
Sweat Test ◽  
Genetic Mutations ◽  
Dna Mutation ◽  
Sweat Chloride ◽  
Sweat Testing

The diagnosis of cystic fibrosis (CF) is based on sweat chloride and DNA mutation testing. A subset of CF patients may have normal sweat chloride levels, thus requiring DNA analysis for confirmation of the diagnosis. These patients may escape diagnosis if sweat testing is the only modality used for screening. Recently, the putative structural gene for CF was localized to chromosome 7. The delta-F508 mutation accounts for approximately 70% of the CF chromosomes identified in North American Caucasians. Over 400 identified mutations constitute the remainder. It is now possible to screen patients for the presence of many of these genetic mutations, thus establishing the diagnosis of CF or defining a carrier state. We report an unusual case of a 17-year-old male with chronic sinusitis, mild pulmonary disease, and pancreatic sufficiency with nondiagnostic sweat chloride levels diagnosed to have CF after DNA analysis. This technique may thus serve as an important tool that pediatricians and otolaryngologists can use to diagnose children suspected of having CF.

scholarly journals History of Newborn Screening for Cystic Fibrosis—The Early Years

2020 ◽  
Vol 6 (1) ◽  
pp. 8 ◽  
Author(s):  
Georges Travert ◽  
Mary Heeley ◽  
Anthony Heeley
Keyword(s):  
Cystic Fibrosis ◽  
Newborn Screening ◽  
21St Century ◽  
Neonatal Screening ◽  
Dried Blood Spots ◽  
Early Years ◽  
Immunoreactive Trypsin ◽  
Blood Spots ◽  
Screening Strategies ◽  
History Of

This review summarises the trajectory of neonatal screening strategies for the detection of cystic fibrosis (CF) using the measurement of Immunoreactive Trypsin (IRT) in dried blood spots (DBS) from 1979 until the beginning of the 21st century when newborn screening (NBS) programmes started to spread throughout many countries, using IRT measurement combined with a CF genotype analysis of DBS.

Screening for cystic fibrosis in newborn infants: results of a pilot programme based on a two tier protocol (IRT/DNA/IRT) in the Italian population

2002 ◽  
Vol 9 (2) ◽  
pp. 60-63 ◽  
Author(s):  
C. Corbetta ◽  
M. Seia ◽  
A. Bassotti ◽  
A. Ambrosioni ◽  
A. Giunta ◽  
...  
Keyword(s):  
Cystic Fibrosis ◽  
Newborn Infants ◽  
Dried Blood Spots ◽  
Screening Strategy ◽  
Sweat Test ◽  
Italian Population ◽  
Screening Protocol ◽  
Oligonucleotide Ligation Assay ◽  
Cftr Mutations ◽  
Immunoreactive Trypsinogen

OBJECTIVE: To assess the performance of a two tier neonatal screening programme (IRT/DNA/IRT) for cystic fibrosis, based on immunoreactive trypsinogen (IRT) followed by direct cystic fibrosis transmembrane conductance regulator (CFTR) gene analysis (based on a panel of up to 31 mutations) in hypertrypsinaemic newborn infants and to compare it with a previous screening protocol. SETTING: The study comprised all the newborn infants in the period 1 October 1998 to 31 December 1999 in the Lombardia region, north western Italy. METHODS: The screening strategy consisted of an immunoreactive trypsinogen assay from dried blood spots, a polymerase chain reaction (PCR) followed by an oligonucleotide ligation assay (PCR-OLA), and a sequence code separation. RESULTS: 104 609 newborn infants were screened. 1457 hypertrypsinaemic infants (1.39%) were analysed with the PCR-OLA assay. 18 newborn homozygotes or compound heterozygotes for CFTR mutations were identified and referred to the cystic fibrosis (CF) centre at a mean age of 3 weeks. 125 infants presenting only one mutation were recalled for a sweat test: a diagnosis of CF was made in 13 infants, and parents of 112 neonates identified as carriers (1:13) received genetic counselling. The remaining 1314 hypertrypsinaemic newborn infants were recalled for IRT retesting and 177 were referred for a sweat test because the second IRT measurement was above the cut off value. Among this group a further two infants were diagnosed with CF (1.1%) leading to a CF prevalence of 1:3170. CONCLUSIONS: This strategy resulted in an early and accurate diagnosis of CF. The IRT/DNA/IRT protocol with an OLA assay was shown to be useful in an Italian population with a genetic heterogeneity, leading to the identification of 94% of infants with CF.

scholarly journals Neonatal screening for cystic fibrosis in Wales and the West Midlands: 1. Evaluation of immunoreactive trypsin test.

1988 ◽  
Vol 41 (7) ◽  
pp. 726-729 ◽  
Author(s):  
H C Ryley ◽  
S M Deam ◽  
J Williams ◽  
M Alfaham ◽  
P H Weller ◽  
...  
Keyword(s):  
Cystic Fibrosis ◽  
Neonatal Screening ◽  
The West ◽  
Immunoreactive Trypsin ◽  
West Midlands

Case report: a child with cystic fibrosis and phenylketonuria

2020 ◽  
Vol 1 (2) ◽  
pp. 38-44
Author(s):  
Irina V. Vakhlova ◽  
Anastasia D. Kazachina ◽  
Olga A. Beglyanina
Keyword(s):  
Cystic Fibrosis ◽  
Case Report ◽  
Clinical Practice ◽  
Neonatal Screening ◽  
Genetic Disorders ◽  
Epileptiform Activity ◽  
Autism Spectrum ◽  
Speech Development ◽  
Inherited Disorders ◽  
Congenital Diseases

Background. In the international clinical practice there have been occasional reports of phenylketonuria (PKU) and cystic fibrosis (CF) found simultaneously in the same patient. Both PKU and CF are the inherited disorders characterized by autosomal recessive type of inheritance. Currently the combination of two or more inherited disorders in one patient is considered to be a clinical rarity.Case description. This is a clinical case of two genetic disorders, CF and PKU, combined in a 5-year old patient who had been followed up since birth. Owing to implementation of neonatal screening for inherited and congenital diseases into clinical practice, during the first month of life the infant was diagnosed with CF (diagnostically significant elevation of immunoreactive trypsin [IRT] at the initial [163.2 ng/mL] and repeat testing on day 21 of life [138.7 ng/mL]) and PKU (phenylalanine [PA] level 15.9 mg/dL). Both disorders have been confirmed by genetic tests, i.e., homozygous DelF508 mutation was found in the cystic fibrosis transmembrane conductance regulator (CFTR) gene, and P281L mutation in the phenylalanine hydroxylase (PAH) gene was also present in homozygous state. Child’s parents strictly adhered to dietary and treatment recommendations. By the age of 5 years the child developed symptoms of neurological disorder and disorder of the respiratory system, cognitive impairment and delay in speech development, subclinical epileptiform activity with high risk of epilepsy, and chronic inflammation of the respiratory tract.Conclusion. This case report demonstrates the important role of neonatal screening in early diagnosis and timely start of therapy, and underscores the importance of continuous medication in such genetic disorders as CF and PKU. On the whole, such approach brings about a relative preservation of functioning of the most affected organs and systems. By the age of 5 years the child does not form bronchiectases, shows no signs of chronic hypoxia, nutritional deficiency or pronounced neurologic deficit, and is at low risk for the development of autism spectrum disorder. At the same time, the larger scale and longer-term observations are required in order to make the unequivocal conclusions about the prognosis of these diseases under conditions of modern-day medical follow-up.

scholarly journals Cystic fibrosis in disguise – the wolf in sheep’s clothing, a case report

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Friederike Wilbert ◽  
Sarah C. Grünert ◽  
Andrea Heinzmann ◽  
Sebastian F. N. Bode
Keyword(s):  
Cystic Fibrosis ◽  
Systemic Disease ◽  
Gastrointestinal Symptoms ◽  
Chloride Concentration ◽  
Failure To Thrive ◽  
Sweat Test ◽  
Upper Airways ◽  
Inborn Errors ◽  
Hepatic Involvement ◽  
Number Of Patients

Abstract Background Childhood hypoglycemia in combination with hepatomegaly is suspicious for inborn errors of metabolism. Cystic fibrosis typically presents with failure to thrive, pulmonary and gastrointestinal symptoms. Hepatic involvement and hypoglycemia can occur in a significant number of patients, although hepatomegaly is uncommon. Case presentation A 28 months old boy was presented with recurrent upper airways infections, progressive lethargy and weight loss. Clinically hepatomegaly was the main presenting feature and hypoglycemia (minimum 1.4 mmol/l) was noted as were elevated transaminases. The patient did not produce enough sweat to analyze it. Infectious causes for hepatitis were excluded and a broad metabolic work-up initiated. A therapy with starch was initiated to control hypoglycemia. In further course loose stools were reported and pancreatic elastase was found to be reduced. A further sweat test yielded pathological chloride concentration and genetic testing confirmed the diagnosis of cystic fibrosis. Conclusions Cystic fibrosis is a systemic disease and less common presentations need to be considered. Even in the age of CF-newborn screening in many countries CF needs to be ruled out in typical and atypical clinical presentations and diagnostics need to be repeated if inconclusive.

scholarly journals Cystic fibrosis

2019 ◽  
Vol 13 (1) ◽  
pp. 39-46
Author(s):  
Jen Standen
Keyword(s):  
Cystic Fibrosis ◽  
Genetic Testing ◽  
Neonatal Screening ◽  
Tertiary Care ◽  
Multidisciplinary Care ◽  
Shared Care ◽  
The Uk

In the UK over 10 000 people live with cystic fibrosis (CF), with 1-in-25 people being carriers of the disease. Multidisciplinary care is provided by tertiary care CF centres, with or without local secondary service shared care agreements. There are still, however, several reasons why CF sufferers or their families present to their GPs. This article aims to provide a brief overview of CF and its management. It also gives the information needed to guide patients about genetic testing and neonatal screening for the disease.

P012 Two-year neonatal screening for cystic fibrosis in Republic of North Macedonia

2021 ◽  
Vol 20 ◽  
pp. S42
Author(s):  
S. Fustik ◽  
V. Anastasovska ◽  
D. Plaseska Karanfilska ◽  
A. Stamatova ◽  
L. Spirevska ◽  
...  
Keyword(s):  
Cystic Fibrosis ◽  
Neonatal Screening
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