scholarly journals Two years of newborn screening for cystic fibrosis in North Macedonia: First experience

2021 ◽  
Vol 24 (1) ◽  
pp. 41-46
Author(s):  
S Fustik ◽  
V Anastasovska ◽  
D Plaseska-Karanfilska ◽  
A Stamatova ◽  
L Spirevska ◽  
...  
Keyword(s):  
Cystic Fibrosis ◽  
Pilot Study ◽  
Newborn Screening ◽  
Chloride Concentration ◽  
Sweat Test ◽  
Sweat Chloride ◽  
Frequent Mutations ◽  
Cftr Mutations ◽  
The Republic ◽  
Cf Transmembrane Conductance Regulator

Abstract There is a widely accepted consensus on the benefits of newborn screening (NBS) for cystic fibrosis (CF) in terms of reduced disease severity, improved quality of life, lower treatment burden, and reduced costs. More and more countries in the world are introducing NBS for CF as a national preventive health program. Newborn screening for CF was introduced in the Republic of North Macedonia (RNM) in April, 2019, after a pilot study of 6 months in 2018. A two-step immunoreactive trysinogen (IRT-IRT) algorithm is performed, and then a sweat test for confirmation/exclusion of the CF diagnosis when the IRT values were both over the cutoff (70.0 and 45.0 ng/mL, respectively). In cases with confirmed diagnosis of CF (a sweat chloride concentration >60.0 mmol/L) or with intermediate sweat test results (a sweat chloride concentration of between 30.0 and 59.0 mmol/L), CF transmembrane conductance regulator (CFTR) mutation analysis is performed. By the end of 2020, over a period of 27 months, including the pilot study period, a total number of 43,139 newborns were screened for CF. Seventeen (0.039%) newborns were diagnosed with CF. In all newly discovered CF cases by screening, the diagnosis was confirmed by determination of the CFTR mutations. The most common CFTR mutation, F508del, was found with an overall incidence of 70.6%. Other more frequent mutations were G542X (11.8%) and N1303K (5.9%). Four mutations were found in one CFTR allele each: G1349D, G126D, 457TAT>G and CFTRdupexon22, with the last one being newly discovered with unknown consequences. An incredibly large difference was found in the incidence of the disease between the Macedonian and Albanian neonatal population, with almost four time higher prevalence among Albanians (1:4530 vs. 1:1284).

Test for the Concentration of Electrolytes in Cystic Fibrosis of the Pancreas Utilizing Pilocarpine by Iontophoresis, by Lewis E. Gibson and Robert E. Cooke,Pediatrics; 1959;24:545–549

PEDIATRICS ◽  
1998 ◽  
Vol 102 (Supplement_1) ◽  
pp. 230-231
Author(s):  
Victor Chernick
Keyword(s):  
Cystic Fibrosis ◽  
Filter Paper ◽  
Direct Injection ◽  
Heat Stroke ◽  
Chloride Concentration ◽  
Hot Water ◽  
Sweat Test ◽  
High Concentration ◽  
Sweat Chloride ◽  
Plastic Bag

Aim. To develop a method for stimulating sweating that is rapid, painless, and avoids the risk of heat stress. Background. Since the discovery that there is a high concentration of sodium and chloride in the sweat of patients with cystic fibrosis of the pancreas in 1953, the sweat test has been performed by placing the patient's body in a plastic bag with or without hot water bottles to stimulate sweating. This method is unsatisfactory because of complications such as hyperpyrexia and heat stroke. Direct injection of a cholinergic agent intradermally is painful and therefore not practical. Methods. A rheostat with a milliampere meter was constructed at a cost of ∼$7 that allowed the iontophoresis of pilocarpine into the skin using negative and positive (2-cm diameter) electrocardiography electrodes. The positive electrode was placed on the flexor surface of the arm over a filter paper soaked in 0.2 mL of 0.2% pilocarpine nitrate. Current (0.2 mA) was applied for 5 minutes and then sweat was collected onto a preweighed filter paper for 30 minutes. Sweat chloride was determined by a polarographic method. Sweat tests were performed on 25 patients with cystic fibrosis (CF), 17 asymptomatic relatives and 27 control patients. Patients with CF had sweat chloride concentration >80 mEq/L; relatives, 32.5 mEq/L (highest 57 mEq/L); and control subjects, 21.1 mEq/L (highest 60 mEq/L). Conclusions. The iontophoresis of pilocarpine into the skin is a rapid, painless, safe, and reliable method for stimulating sweating and facilitating the determination of sweat chloride concentration.

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.

scholarly journals P045 Results from a newborn screening (NBS) pilot study for cystic fibrosis in the Republic of Macedonia

2019 ◽  
Vol 18 ◽  
pp. S69
Author(s):  
S. Fustik ◽  
V. Anastasovska ◽  
D. Plaseska-Karanfilska ◽  
L. Spirevska ◽  
A. Stamatova ◽  
...  
Keyword(s):  
Cystic Fibrosis ◽  
Pilot Study ◽  
Newborn Screening ◽  
Republic Of Macedonia ◽  
The Republic

scholarly journals Newborn Screening for Cystic Fibrosis: Infant and Laboratory Factors Affecting Successful Sweat Test Completion

2020 ◽  
Vol 7 (1) ◽  
pp. 1
Author(s):  
Ambika Shenoy ◽  
Dina Spyropoulos ◽  
Kathleen Peeke ◽  
Dawn Smith ◽  
Michael Cellucci ◽  
...  
Keyword(s):  
Cystic Fibrosis ◽  
Newborn Screening ◽  
Gestational Age ◽  
Diagnostic Testing ◽  
Sweat Test ◽  
Inherited Disease ◽  
Success Rates ◽  
Factors Affecting ◽  
Laboratory Staff ◽  
Sweat Chloride

Newborn screening (NBS) for Cystic Fibrosis (CF) has revolutionized the diagnosis of this inherited disease. CF NBS goals are to identify, diagnose, and initiate early CF treatment to attain better health outcomes. Abnormal CF NBS infants require diagnostic analysis via sweat chloride testing (ST). During ST, insufficient sweat volume collection causes a “quantity not sufficient” (QNS) test result and may delay CF diagnosis. The CF Foundation recommends QNS rates <10% for infants <3 months, but many CF Centers experience difficulties meeting this standard. Our quality improvement (QI) study assessed infant and laboratory factors contributing to ST success and QNS rates from 2017–2019. Infants’ day of life (DOL) at successful ST completion was analyzed according to infant factors (birth weight (BW), gestational age, ethnicity, and sex). Laboratory factors and procedures affecting ST outcomes were also reviewed. At our institution, BW and gestational age were the infant factors found to significantly affect DOL at ST completion. ST education, reduced number of laboratory technicians, and direct observation during ST completion also improved ST success rates. This study supports QI measures and partnerships between CF centers and laboratory staff to identify and improve ST QNS rates while sustaining practices to ensure timely CF diagnostic testing.

scholarly journals Screening for the Most Common Mutations of CFTR Gene among Egyptian Children with Difficult-to-Treat Asthma

2020 ◽  
Vol 09 (03) ◽  
pp. 164-170
Author(s):  
Mohammad Al-Haggar ◽  
Engy Osman ◽  
Abdel-Rahman Eid ◽  
Tarek Barakat ◽  
Samar El-Morsi
Keyword(s):  
Cystic Fibrosis ◽  
Cftr Gene ◽  
Sweat Test ◽  
Amplification Refractory Mutation System ◽  
Single Mutation ◽  
Sweat Chloride ◽  
Increased Risk ◽  
Egyptian Children ◽  
Mutation System ◽  
Cftr Mutations

AbstractCystic fibrosis (CF) is panethnic autosomal recessive disease that affects the exocrine glands of pancreas, lungs, and intestine. It is often misdiagnosed in developing countries as difficult-to-treat asthma. We enrolled 150 Egyptian families with one or more probands who were complaining of difficult-to-treat asthma, and 112 cases were studied extensively through history taking including pedigree construction and clinical examination. In addition, spirometry and computed tomography of the chest were done in selected cases. All cases were subjected to quantitative sweat chloride test and molecular screening for the three most common mutations of cystic fibrosis transconductance regulator (CFTR) gene (ΔF508, G542X, W1282X) using amplification refractory mutation system (ARMS) technique. Probands of difficult-to-treat asthma comprised 66 males and 46 females; their age range was 1 to 14 years. Sixty-one probands (54.5%) were carriers of one or more of the studied mutations (36 cases and 25 carriers). Six carriers of single mutations had mild respiratory symptoms and negative sweat test. The most common allele was ΔF508, 60 alleles in 56 individuals (4 were homozygous ΔF508/ΔF508) followed by W1282X in 25 individuals and G542X in 12 individuals. Allele W1282X had an increased risk of recurrent chest infection and bronchiectasis. Moreover, cases with two mutations had more severe symptoms compared with those with a single mutation. CFTR mutations and CF-related syndromes are not rare as thought in Egypt, especially among the high-risk difficult-to-treat asthma. The readily available ARMS technique is recommended for ΔF508 and/or W1282X screening on priority basis among these children.

scholarly journals CFTR gene analysis in patient with atypical cystic fibrosis

2004 ◽  
Vol 23 (4) ◽  
pp. 351-354
Author(s):  
Aleksandra Nikolic ◽  
Aleksandra Divac ◽  
Nada Bogdanovic ◽  
Marija Mitic-Milikic ◽  
Dragica Radojkovic
Keyword(s):  
Cystic Fibrosis ◽  
Mutation Detection ◽  
Molecular Genetic ◽  
Sweat Test ◽  
Molecular Genetic Testing ◽  
Indirect Methods ◽  
Frequent Mutations ◽  
Cftr Mutations ◽  
Atypical Presentations ◽  
Direct And Indirect Methods

This paper reports a case of a patient presenting with atypical cystic fibrosis whose sweat test shows borderline values. In vast majority of cases the sweat test is essential diagnostic tool for establishing the diagnosis of cystic fibrosis, but only after the molecular genetic testing the diagnosis can be confirmed. The patient was found to be compound heterozygote for two CFTR mutations, F508del and D1152H. The presence of F508del mutation was analyzed by PSM method, while the screening for the second mutation was performed using DGGE. The strategy of mutation detection in cystic fibrosis patients, especially those with atypical presentations who carry less frequent mutations, should include both direct and indirect methods of molecular diagnostics.

Evaluation of a cystic fibrosis screening system incorporating a miniature sweat stimulator and disposable chloride sensor.

1986 ◽  
Vol 32 (5) ◽  
pp. 850-853 ◽  
Author(s):  
W J Warwick ◽  
N N Huang ◽  
W W Waring ◽  
A G Cherian ◽  
I Brown ◽  
...  
Keyword(s):  
Cystic Fibrosis ◽  
Chloride Concentration ◽  
Test System ◽  
Sweat Test ◽  
Sweat Chloride ◽  
The Subject ◽  
New System ◽  
Chloride Concentrations ◽  
Cystic Fibrosis Screening ◽  
Center Study

Abstract A new sweat test (CF Indicator; Medtronic, Inc.) for cystic fibrosis (CF) features a compact, portable configuration of electrodes that dispense pilocarpine for iontophoresis. A disposable chloride sensor patch absorbs a specified volume of sweat, in which the chloride concentration is immediately determined as less than 40, 40-60, or greater than 60 mmol/L. We assessed the performance of the system in a five-center study, in relation to the clinical diagnosis and to the Gibson-Cooke sweat test (GCST) as a control test. With sweat chloride concentrations of less than or equal to 40 mmol/L defined as normal and greater than 40 mmol/L as indicating persons at risk for CF, the new system showed 91% specificity and 100% sensitivity for CF, as compared with 92.8% and 100%, respectively, for the GCST. When we used sweat chloride concentrations of less than or equal to 60 mmol/L as probably normal and greater than 60 mmol/L as probably indicative of CF, the new system showed a 99.1% specificity and 98.6% sensitivity, vs 97.8% specificity and 97.9% sensitivity for the GCST test. In both procedures, occasionally insufficient sweat was collected, and this appeared related to the age of the subject. We conclude that the new sweat test system is potentially useful in physicians' offices, in clinics, and similar settings.

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.

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