Diagnosis Of Cystic Fibrosis Research Articles

Gradual increase in sweat chloride concentration is associated with a higher risk of CRMS/CFSPID to CF reclassification.

Universal implementation of cystic fibrosis (CF) newborn screening (NBS) has led to the diagnostic dilemma of infants with CF screen-positive, inconclusive diagnosis (CFSPID), with limited guidance regarding prognosis and standardized care. Rates of reclassification from CFSPID to CF vary and risk factors for reclassification are not well established. We investigated whether clinical characteristics are associated with the risk of reclassification from CFSPID to a CF diagnosis. Children with a positive CF NBS were recruited from two sites in California. Retrospective, longitudinal, and cross-sectional data were collected. A subset of subjects had nasal epithelial cells collected for CF transmembrane conductance regulator(CFTR) functional assessment. Multivariate logistic regression was used to assess the risk of reclassification. A total of 112 children completed the study (CF = 53, CFSPID = 59). Phenotypic characteristics between groups showed differences in pancreatic insufficiency prevalence, immunoreactive trypsinogen (IRT) levels, and Pseudomonas aeruginosa (PSA) colonization. Spirometry measures were not different between groups. Nasal epithelial cells from 10 subjects showed 7%-30% of wild-type (WT)-CFTR (wtCFTR) function in those who reclassified and 27%-67% of wtCFTR function in those who retained the CFSPID designation. Modeling revealed that increasing sweat chloride concentration (sw[Cl- ]) and PSA colonization were independent risk factors for reclassification to CF. Increasing sw[Cl- ] and a history of PSA colonization are associated with the risk of reclassification from CFSPID to CF in a population with high IRT and two CFTR variants. A close follow-up to monitor phenotypic changes remains critical in this population. The role of CFTR functional assays in this population requires further exploration.

A Case Report of the First Filipino Infant Diagnosed with Cystic Fibrosis through the Philippine Newborn Screening Program

Cystic Fibrosis (CF) is a rare condition among Asians and has not been reported in the Philippines as of this time.The inclusion of this disease in the Philippines’ Expanded Newborn Screening Program (ENBS) has provided thisFilipino family the opportunity of early detection and appropriate management of this condition that could ensure the survival of the proband and his other surviving siblings.Here we present a case of a 24-month-old male who had a positive Expanded Newborn Screening (ENBS) test forcystic fibrosis and eventually underwent further tests to confirm a homozygous deletion of exons 1 - 2 of the CFTR gene. He subsequently had recurrent pneumonia but is being managed by a team consisting of a pulmonologist, gastroenterologist, and a metabolic dietitian. The proband had an older sibling whose Newborn Screening (NBS) test was normal and who eventually expired from recurrent bouts of pneumonia. This sibling was never managed as a case of cystic fibrosis. Implications on the diagnosis and management of CF in the local setting is also discussed.The importance of an appropriate CF panel customized to the local population should be reiterated and carrier testing should be encouraged to help with proper family counseling for future pregnancies for the family involved.

Frequency of F508del Variant in Patients with Cystic Fibrosis from Paraguay

Cystic fibrosis (CF) is an autosomal recessive disorder and is caused by variants in the Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) gene. We aimed to study the frequency of the F508del variant, the most common variant worldwide, in patients with CF from Paraguay. The frequency of the F508del variant in Paraguayan patients with a clinical diagnosis of CF was assessed using a polymerase chain reaction followed by the sequencing of the PCR products. 43 of the 86 patients (50%) were homozygous for the F508del variant, 28 were heterozygous (32.56%), and the remaining 15 (17.44%) were non-carriers. In terms of alleles, there were 114 mutated (114/172 or 66.28%) and 58 did not correspond to this variant (58/172 or 33.72%). This is the first study of the frequency of the F508del variant in patients with CF in Paraguay. This information is of utmost relevance when planning and offering treatments from health services.

Результаты коррекции недостаточности питания у детей с муковисцидозом с использованием гиперкалорийной полуэлементной лечебной смеси для энтерального питания: наблюдательное исследование

Objective. To evaluate the dynamics of anthropometric indices and body composition in children with cystic fibrosis (CF) against the background of dietary correction with the use of semi-elemental and polymeric hypercaloric therapeutic formulas. Patients and methods. This was a single-center, retrospective, comparative study. Medical records of 40 children aged 5 to 10 years with a confirmed diagnosis of CF and a body mass index (BMI) less that the 50th percentile were analyzed. Children in the study group (n = 20) received a hypercaloric semi-elemental formula based on hydrolyzed protein; children in the comparison group (n = 20) received a hypercaloric formula for enteral nutrition based on whole protein. Both groups were comparable in age, sex, anthropometric and clinical characteristics. We assessed the comparative dynamics of anthropometric indices and body composition determined by bioimpedance analysis against the background of dietary correction for 90 ± 7 days. Results. The use of hypercaloric semi-elemental formula based on hydrolyzed protein was accompanied by an average increase in body weight by 1.8 kg, height by 2.2 cm, BMI by 0.7 kg/m2, and skeletal muscle mass by 1.7%. Similar results were obtained in the comparison group. No statistically significant differences between the groups regarding examined indicators were found. Conclusion. The retrospective analysis of using a hypercaloric semi-elemental formula based on hydrolyzed whey protein for the correction of nutritional deficiency in children with CF aged 5 to 10 years indicates its clinical efficacy for this category of patients. Key words: cystic fibrosis, children, malnutrition, hypercaloric formula, enteral nutrition, semi-elemental formula, intestinal syndrome, Peptamen Junior 1.5, malabsorpt

Evaluation of specificity and sensitivity of IRT/IRT protocol in the cystic fibrosis newborn screening program: 6-year experience of three tertiary centers.

We aimed to evaluate cutoff values of immunoreactive trypsinogen (IRT)/IRT and determine relationship between IRT values and clinical characteristics of children with cystic fibrosis (CF). This study is cross-sectional study. Data of children with positive newborn screening (NBS) between 2015 and 2021 were evaluated in three pediatric pulmonology centers. Age at admission, sex, gestational age, presence of history of meconium ileus, parental consanguinity, sibling with CF, and doll-like face appearance, first and second IRT values, sweat chloride test, fecal elastase, fecal fat, biochemistry results, and age at CF diagnosis were recorded. Sensitivity and specificity of IRT cutoff values were evaluated. Of 815 children with positive NBS, 58 (7.1%) children were diagnosed with CF. Median values of first and second IRT were 157.2 (103.7-247.6) and 113.0 (84.0-201.5) μg/L. IRT values used in current protocol, sensitivity was determined as 96.6%, specificity as 17.2% for first IRT, and 96.6% sensitivity, 20.5% specificity for second IRT. Positive predictive value (PPV) was determined as 7.1%. When cutoff value for first IRT was estimated as 116.7μg/L, sensitivity was 69.0% and specificity was 69.6%, and when cutoff value was set to 88.7μg/L for second IRT, sensitivity was 69.0% and specificity was 69.0%. Area under curve was 0.757 for first and 0.763 for second IRT (p < 0.001, p < 0.001, respectively). PPV was calculated as 4.3%. Conclusion: Although sensitivity of CF NBS is high in our country, its PPV is significantly lower than expected from CF NBS programs. False-positive NBS results could have been overcome by revising NBS strategy. What is Known: • Although immunoreactive trypsinogen elevation is a sensitive test used in cystic fibrosis newborn screening, its specificity is low. • In countries although different algorithms are used, all strategies begin with the measurement of immunoreactive trypsinogen in dried blood spots. What is New: • In our study, it was shown that use of the IRT/IRT protocol for cystic fibrosis newborn screening is not sufficient for the cut-off values determined by the high number of patients. • Newborn screening strategy should be reviewed to reduce false positive newborn screening results.

Perceptions of airway gene therapy for cystic fibrosis

ABSTRACT Background Airway gene therapy could produce lasting benefit for cystic fibrosis (CF) lung disease, however patient and public support is critical for successful adoption. Research design and methods Two separate quantitative online surveys were conducted to examine perceptions towards airway gene therapy for CF among people with CF, their families, and members of the public. Data was collected from a total of 213 participants across both studies, with 43 having a diagnosis of CF, 122 having a family member with CF, and 135 knowing someone with CF. Results Participants in both studies displayed positive perceptions towards gene therapy and were supportive of involvement in CF gene therapy trials. Around 50% hoped gene therapy could provide a cure. In Study 1 gene therapy was the most important research area, but in Study 2 this was new daily drugs. Almost all thought gene therapy was still required even if modulators already improved quality of life. Conclusion The factors that influence acceptance, whether trials would be positively viewed, and whether individuals with CF are receptive to gene therapy, are essential to determine prior to clinical trials. Our findings indicate people have positive opinions about airway gene therapy for CF, but further education is vital.

Variation in cystic fibrosis newborn screening algorithms in the United States.

Cystic fibrosis (CF) newborn screening (NBS) algorithms in the United Statesvary by state. Differences in CF NBS algorithms could potentially affect the detection rate of CF newborns and lead to disparities in CF diagnosis amongst different racial and ethnic groups. Generate a database of CF NBS algorithms in the United States andidentify processes that may potentially lead to missed diagnoses or lead to healthcare disparities. We sent an online survey to state and regional CF and NBS leaders about the type and threshold of immunoreactive trypsinogen (IRT) cutoff used and methods used for CFTR gene variant analysis. Follow-up by email and phone was done to ensure a response from every state, clarify responses, and resolve discordances. There is wide variation in the NBS algorithms employed by different states. Approximately half the states use a floating IRT cutoff, and half use a fixed IRT cutoff. CFTR variant analysis also varies widely, with two states analyzing only for the F508del variant and four states incorporating CFTR gene sequencing. The other states use CFTR variant panels ranging from 23 to 365 CFTR variants. CF NBS algorithms vary widely amongst the different states in the United States, which affects the ability of CF NBS to diagnose newborn infants with CF consistently and uniformly across the country and potentially may miss more infants with CF from minority populations. Our results identify an important area for quality improvement in CF NBS.

451: MANAGEMENT OF STENOTROPHOMONAS MALTOPHILIA PNEUMONIA IN MECHANICALLY VENTILATED PATIENTS

Introduction: Stenotrophomonas maltophilia is a gram negative opportunistic pathogen that most often causes infections in critically ill patients. S. maltophilia infections are associated with high morbidity and mortality. Common treatment options include sulfamethoxazole/trimethoprim (SMX/TMP), levofloxacin, and tetracyclines. SMX/TMP has been shown to have resistance rates up to 19%, and levofloxacin has shown minimal resistance rates (2%). Regardless of resistance rates, S. maltophilia is associated with a treatment failure rate of around 30%. The objective of this study is to evaluate the effectiveness of monotherapy treatment with SMX/TMP or levofloxacin in critically ill patients with S. maltophilia pneumonia on mechanical ventilation. Methods: Retrospective analysis of patients >/=18 years of age with a positive respiratory culture for S. maltophilia between January 1, 2018, to August 31, 2021. At the time of culture patients must have been on mechanical ventilation for at least 48 hours and treated with monotherapy SMX/TMP or levofloxacin for at least 48 hours. Patients were excluded if they received less than 48 hours of monotherapy, received concomitant treatment with an additional agent with activity agents S. maltophilia (minocycline, ceftazidime, cefiderocol), were pregnant, received combination therapy, had a diagnosis of cystic fibrosis, or had a history of S. maltophila positive culture within the previous 12 months. Results: A total of 105 patients were assessed for eligibility and 92 met inclusion criteria. Of these patients, 51 (55%) received SMX/TMP and 41 (45%) received levofloxacin. Treatment failure occurred more often in those treated with levofloxacin 20% compared to SMX/TMP 16%, p=0.045. Mortality was greater in the levofloxacin group 37% vs. 15%, p=0.011. Clinical cure, 30-day microbiological cure, ICU length of stay and hospital length of stay were similar between groups. Acute kidney injury occurred significantly more in patients treated with SMX/TMP. Conclusions: SMX/TMP was associated with less treatment failure and mortality compared to levofloxacin when treating S. maltophilia pneumonia in patients on mechanical ventilation. A large multicenter cohort study comparing SMX/TMP and levofloxacin is warranted to validate these findings.

CFTR pharmacological modulators: A great advance in cystic fibrosis management

Cystic fibrosis is a severe monogenic disease that affects around 7400 patients in France. More than 2100 mutations in the cystic fibrosis conductance transmembrane regulator (CFTR), the gene encoding for an epithelial ion channel that normally transports chloride and bicarbonate, lead to mucus dehydration and impaired bronchial clearance. Systematic neonatal screening in France since 2002 has enabled early diagnosis of cystic fibrosis. Although highly demanding, supportive treatments including daily chest physiotherapy, inhaled aerosol therapy, frequent antibiotic courses, nutritional and pancreatic extracts have improved the prognosis. Median age at death is now beyond 30 years. Ivacaftor was the first CFTR modulator found to both reduce sweat chloride concentration and improve pulmonary function in the rare CFTR gating mutations. Combinations of modulators such as lumacaftor + ivacaftor or tezacaftor + ivacaftor were found to improve pulmonary function both in patients homozygous for the F508del mutation characterized by the lack of CFTR protein and those heterozygous for F508del with minimal CFTR activity. The triple combination of ivacaftor + tezacaftor + elexacaftor was recently shown to significantly improve pulmonary function and quality of life, to normalize sweat chloride concentration, and to reduce the need for antibiotic therapy in patients with at least one F508del mutation (83% in France). These impressive data, however, need to be confirmed in the long term. Nevertheless, it is encouraging to hear treated patients testify about their markedly improved quality of life and to observe that the number of lung transplants for cystic fibrosis decreased dramatically in France after 2020, despite the COVID pandemic, with no increase in deaths without lung transplant.

PECULIARITIES OF CYSTIC FIBROSIS IN NEWBORN ON THE EXAMPLE OF A CLINICAL CASE

Cystic fibrosis is a severe genetic disease, which is inherited in an autosomal recessive manner and is characterized by a polyorganic clinical presentation with predominantly exocrine, respiratory and digestive gland involvement. Every year more than 45 000 children are born worldwide with this genetic disease. According to official statistics, 674 children with cystic fibrosis are registered in Ukraine, 25 of them in the Vinnytsia region. The disease is caused by a mutation in the gene encoding the cystic fibrosis transmembrane conductance regulator (CFTR). The F508del mutation is most common in the paediatric population (19-34%). The most common clinical manifestations of cystic fibrosis in newborns are disorders of the gastrointestinal tract, pancreas, hepatobiliary system and respiratory system. In 20% of newborns, one of the earliest manifestations of cystic fibrosis is meconial ileus, which may pose a risk of complications such as meconium peritonitis, sputum, gangrene or intestinal necrosis. Early diagnosis with neonatal screening, improved care for the neonatal manifestations of meconial ileus and adequate medical follow-up by a multidisciplinary team of specialists, and improved lifelong replacement fermentation therapy have a significant impact on the life expectancy of patients with cystic fibrosis.This article presents a clinical case of early diagnosis of cystic fibrosis in a newborn. When meconial ileus is present and cysticfibrosis is suspected in a newborn, early genetic diagnosis is mandatory, in addition to timely and correctly performed neonatal screening. Comprehensive and timely treatment leads to improvement in cystic fibrosis patients and slows down the development of pathological changes in the bronchopulmonary and hepatobiliary systems.Conclusions. Prevention of a severe course of cystic fibrosis is in early detection of the disease during neonatal screening, indiagnosis at the first signs of the disease and early start of pathogenetic treatment, which improves the quality of life of patients.

Exploring parental cystic fibrosis disclosure to well children.

Cystic fibrosis (CF), a genetic disease and chronic illness, affects multiple organ systems and requires exceptional medical care and treatment. Few studies have assessed the diagnosis disclosure process to well children when their sibling(s) have CF, and none have evaluated the association between parental knowledge of CF and the disclosure of CF. The objectives of this study were to assess parental understanding of CF, demonstrate the most commonly shared topics and their frequencies of discussion with well children, and identify associations between parental understanding of CF and aspects of the disclosure process to well children. Parents were recruited from CF support organizations and asked to complete an online, anonymous survey. Individuals were eligible to participate in the study if they had at least one living child with CF and at least one living child without CF. Completed surveys from 48 individuals revealed that most parents began discussing a sibling's diagnosis of CF with the first-born well child at 5.4 years old. Topics related to CF were discussed openly and as needed with their well children (n=44). The most frequently discussed topic, and the topic ranked most important (1.93 of 5, SD: 1.17) by 40 participants (90.9%), was medical concerns and treatment for CF. Fewer parents (n=18, 40.9%) reported discussing the financial impact of CF, and many ranked this as least important to share (4.64 of 5, SD: 0.75). The CF knowledge assessment revealed that participants were well-informed about CF, with a mean total score of 8.9/10 (SD: 0.91). There were no associations between CF knowledge assessment scores, education level, income,and the topics discussed with well children. These results can be utilized by genetic counselors and other healthcare specialists in discussion with parents about the disclosure process of a diagnosis of CF to well children.

Cystic Fibrosis Screen Positive, Inconclusive Diagnosis Genotypes in People with Cystic Fibrosis from the U.S. Patient Registry.

Rationale: Variants within the cystic fibrosis (CF) transmembrane conductance regulator gene, CFTR, that are of unknown significance or are categorized as non-CF causing may be observed in persons with CF. These variants are frequently detected in children with inconclusive newborn screen results and, in some cases, may be associated with a benign presentation in early childhood that progresses to a CF phenotype later in life. Objectives: To analyze data from individuals enrolled in the U.S. Cystic Fibrosis Foundation Patient Registry who have received a diagnosis of CF and who have variants found in a population of children with a CF screen positive, inconclusive diagnosis (CFSPID). Methods: This retrospective review analyzed registry data from individuals with a diagnosis of CF who also harbor one or more variants of interest because of their frequency within a CFSPID population and/or their interpretation as non-CF causing. Three groups were defined by the number of CF-causing variants identified (CF-Cx2, CF-Cx1, and CF-Cx0), which were reported in addition to the variant(s) of interest. Multivariate quantile regression modeling of the outcome for forced expiratory volume in 1 second (FEV1) generated a disease severity score for each person determined by six selected variables. Median scores were calculated for the three groups. Results: Patients carrying one CF-causing variant and at least one variant of interest (CF-Cx1) had higher median disease severity scores compared with those carrying CF-Cx2, suggesting a milder phenotype (P < 0.05). However, there was no statistically significant difference in scores between CF-Cx2 and the two other groups combined (CF-Cx1 and CF-Cx0; P = 0.33). Analysis revealed that the CF-Cx1 and CF-Cx0 groups, when compared with the CF-Cx2 group, had later median diagnoses (8 years vs. newborn; P < 0.0001), lower median sweat chloride (48 mmol/L vs. 94.5 mmol/L; P < 0.0001), lower prevalence of pancreatic insufficiency (29% vs. 78%; P < 0.0001), and higher median FEV1% predicted (95% vs. 87%; P = 0.0002). Conclusions: Individuals with CF who have specific variants frequently identified in children with CFSPID have a similar range of disease severity scores compared with those who have two CF-causing variants, but a milder phenotype overall. Variants that should be given careful scrutiny because of their high prevalence are G576A+R668C, T854T, R75Q, F1052V, R1070W, R31C, and L967S.

β-adrenergic sweat test in children with inconclusive cystic fibrosis diagnosis: Do we need new reference ranges?

Investigating inconclusive cystic fibrosis (CF) diagnosis in children is difficult without advanced cystic fibrosis transmembrane conductance regulator (CFTR) function tests. This study investigated the utility of beta (β)-adrenergic sweat test to exclude CF in participants with inconclusive diagnosis (CF suspects) in South Africa. β-adrenergic sweat test and sweat chloride tests (SCT) were performed simultaneously in CF suspects and adult controls (healthy, CFTR heterozygotes and CF). Cholinergic and β-adrenergic induced sweat rate was measured by evaporimetry (transepithelial water loss [TEWL]: g H2 O/m2 /h) following intradermal injections. Next-generation sequencing of CFTR was performed in CF suspects. CF diagnosis was defined by genotype. Thirty-seven controls (10 healthy, 14 CF, 13 CFTR heterozygotes) and 32 CF suspects (26 children; 6 adults) were enrolled. Six were excluded from formal analyses due to β-adrenergic sweat test failure. In adults, evaporimetry was superior to SCT for diagnosis of CF with β-adrenergic:cholinergic ratio TEWL ≤ 0.05 achieving 100% sensitivity and specificity. Twenty-two CF suspect children (age range: 3.4-15.6 years) completed β-adrenergic sweat testing of which none had CF confirmed by genotyping: β-adrenergic:cholinergic ratio > 0.05 successfully excluded CF in all but one child who was CFTR heterozygous. Median peak β-adrenergic TEWL and β-adrenergic:cholinergic ratio in CFTR negative and CFTR heterozygous children was significantly lower than adult controls. β-adrenergic sweat test is more accurate than SCT for excluding CF in children with inconclusive diagnosis. Established reference ranges for β-adrenergic sweat test may not be suitable for children due to lower β-adrenergic sweat secretion compared to adults.

Investigating the genetic profile of familial atypical cystic fibrosis patients (DeltaF508-CFTR) with neonatal biliary atresia.

Biliary atresia (BA) is a progressive inflammatory process of the biliary tree resulting in biliary obstruction. No single known genetic or environmental factor has been established to cause BA. Cystic fibrosis (CF) is a rare cause of neonatal cholestasis, and it has never been described in familial BA cases. Here, we investigate two siblings of first-degree consanguineous parents presenting with neonatal BA. Shortly after the Kasai operation, the proband developed severe respiratory symptoms attributable to a missed CF diagnosis. This was discovered after re-investigating the family history, which revealed a first-degree cousin with CF who did not manifest BA. Afterwards, we identified a pathogenic variant (DeltaF508) in CFTR in both BA-affected siblings along with their cousin. This intrigued us to study the molecular etiology behind the familial BA presentations, which exclusively contributed to BA-pathogenesis in BA-CF-affected siblings and not in their CF-only affected cousin. We applied a multistep approach to investigate the variant profile of both siblings' and their cousin's exomes. We curated the genes whose variants were shared by the BA-CF siblings but absent or heterozygous in their CF-only-affected cousin. Consequently, we identified three candidate genes (SNAPC4, UCK1, and ZHX2) besides CFTR. We propose that these genes act cumulatively or individually in inducing BA-pathogenesis-either by aggravating the biliary damage in the context of CF or increasing the susceptibility of BA as a separate CF-comorbidity. To our knowledge, this is the first report of DeltaF508 in CFTR with familial neonatal BA cases.

Is There any Association between Fecal Calprotectin Levels and Cystic Fibrosis?

Background: Early diagnosis of cystic fibrosis (CF) and hence the initiation of symptomatic and prophylactic treatment can help improve the outcomes of CF patients. Fecal calprotectin (FC) is a marker of inflammation in the intestinal tract that is elevated in several gastrointestinal inflammatory diseases, but little is known about its value in CF. Objectives: This study, therefore, aimed to survey the associations of FC among CF patients and its correlation with the clinical manifestations of CF. Methods: This descriptive cross-sectional study was performed on 52 children with CF visiting the Children’s Hospital of Tabriz, Iran, during 2018-2019, selected through the census sampling method. The calprotectin values of &lt;50 μg/g were considered normal. Results: There was no clinically relevant association among FC levels concerning pancreatic insufficiency, diabetes, and airway colonization with Pseudomonas. In a comparison of the number of exacerbations and Forced Expiratory Volume in the first second (FEV1), the levels of electrolytes showed no significant difference between patients with normal calprotectin and elevated FC. The results of the performed analysis indicated no significant difference between the low-fecal elastase and the FC levels in patients with CF (P=0.53). Conclusion: Demographic and clinical parameters, such as age, gender, FEV1, or Body Mass Index, had no clinically significant relationship with FC. However, serial and longitudinal calprotectin levels should also be checked, which may have clinical relevance during symptomatic episodes.

A Review of Patients with False Positive Cystic Fibrosis Screening Tests in the Light of Current Literature

Amaç: Kistik fibrozis (KF); tekrarlayan akciğer enfeksiyonları, mekonyum ileusu, pankreatik yetmezlik gibi bulgularla seyreden ve birden fazla sistemi tutabilen, yenidoğan döneminden başlayabilen kronik bir hastalıktır. Kistik fibrozis otozomal resesif geçişli bir hastalık olup ülkemizde sıklığının 1/2500-1/3000 olduğu düşünülmektedir1. Hastalığın erken tanısını koyup erken tedaviye başlayabilmek için Türkiye’de 2015 yılında yenidoğan tarama programlarına KF tarama programı eklendi ve İmmünoReaktif Tripsinojen (IRT) enzimini ölçmeye dayanan bir testtir2. Araştırmamızda, iki KF tarama testide pozitif olup Çocuk Sağlığı İzlem Polikliniği’ne gönderilen bebekleri klinik ve ter testi sonucuyla beraber değerlendirerek KF tarama testi yanlış pozitifliklerin nedenlerini irdelemeyi amaçladık. Yöntem: Retrospektif yaptığımız bu çalışmada KF yenidoğan tarama testleri pozitif olduğu için 2018 yılında gönderilen bebeklerimizin ter testleri sonuçlarını ve klinik bilgilerini dosya kayıtlarından elde ettik. Çalışmaya başlamadan önce Etik Kurulu onayı alındı. Klinik ve ter testi sonuçlarına göre KF riski yüksek olan hastalarımız kesin tanı için KF referans hastanesine yönlendirilmişti. KF tanısı almayan ve tarama testleri yanlış pozitif olan vakaların sosyodemografik bilgileri, öykü, fizik muayene, prognozları ve test bilgileri ile tarama testleri sonuçları birlikte değerlendirilerek yanlış pozitifliğe neden olan faktörler istatiksel olarak analiz edildi. Bulgular: Çalışmaya aldığımız 16 vakanın demografik bilgileri ve prognozları çizelgelerde belirtilmektedir. Polikliniğe başvurdukları ilk gün yaşları ortalama 133,75±82,15 günlüktü (%57’si erkek bebekti). Doğum haftası ve tartısı, YDYBÜ’ sine yatış ve antibiyotik alma süresi, uzamış sarılık, kardeş ölümü ve ilk mekonyumun gecikme öyküsü tarama testleriyle istatiksel olarak anlamlı ilişkili bulunurken diğer bulgularla aralarında anlamlı ilişki bulunmadı. Sonuç: Bu çalışmada KF tarama testinde yanlış pozitifliğin olabileceği ve bunu açıklayan faktörler olduğu tekrar vurgulanmış oldu. KF tarama testinin yanlış pozitifliğinin fazla olduğu bilinmesine rağmen tarama testi pozitif olan her hastaya ter testi kesinlikle yapılmalıdır. Kliniğinde şüpheli bir bulgusu olan ve/veya ter testi arada bir değerde olan ve/veya KF risk faktörü taşıyan her bebek tekrar değerlendirmeli ve kliniğinin ilerleyen aylarda da çıkabileceği unutulmamalıdır.

100 Improving the experience for patients and families with new diagnoses of cystic fibrosis

100 Improving the experience for patients and families with new diagnoses of cystic fibrosis

Reporting Two Novel Mutations in Two Iranian Families with Cystic Fibrosis, Molecular and Bioinformatic Analysis

Cystic fibrosis is the most common heredity disease among the Caucasian population. More than 350 known pathogenic variations in the CFTR gene (NM_000492.4) cause cystic fibrosis. Herein, we report the outcome of our investigation of two unrelated Iranian families with cystic fibrosis patients. We conducted phenotypic examination, segregation, and linkage analysis, and CFTR gene sequencing to define causative mutations. Two novel mutations were found. One was a deletion causing frameshift, c.299delT p.(Leu100Profs*7) and the second one was a missense mutation, c.1857G>T at nucleotide binding domain 1 of the CFTR protein. Haplotype segregation data supported our new mutation findings. These findings expand the spectrum of CFTR pathogenic variations and can improve prenatal diagnosis and genetic counseling for cystic fibrosis.

A CASE OF AUTOSOMAL-DOMINANT HYPER-IGE SYNDROME MASQUERADING AS CYSTIC FIBROSIS

A CASE OF AUTOSOMAL-DOMINANT HYPER-IGE SYNDROME MASQUERADING AS CYSTIC FIBROSIS

348 Indiana University School of Medicine continuing medical education course targeting sweat testing in the diagnosis of cystic fibrosis successfully enhanced education for health care teams

348 Indiana University School of Medicine continuing medical education course targeting sweat testing in the diagnosis of cystic fibrosis successfully enhanced education for health care teams