Amaç: Primer immün yetmezliği (PİY) ve kistik fibrozis (KF) hastalığı olan çocukların ve birincil bakım veren ebeveynlerinin COVID-19 pandemisi sırasında kaygı düzeylerini ölçmeyi ve kaygı düzeylerinin hastaların klinik özellikleri ile ilişkisini incelemeyi amaçladık. Yöntemler: Çalışmaya 0-18 yaş arası 28 PİY hastası ve 0-18 yaş arası 28 KF hastası ve birincil bakım veren ebeveynleri dahil edildi. Kontrol grubuna çocuk polikliniği' ne başvuran ve kronik hastalığı olmayan 0-18 yaş arası 28 hasta ve onların birincil bakım veren ebeveynleri alındı. 8 yaş ve üzeri çocuklarda anksiyetenin durumunu ve özelliklerini değerlendirmek için Çocukluk Çağı Kaygı Bozuklukları Öz bildirim Ölçeği Çocuk Formu, ebeveynlere ise Beck depresyon ölçeği uygulandı. Bulgular: Çocuklarda anksiyete bozukluklarını tarama ölçeğinin sorularını 8 yaş üstü 54 hasta cevaplamış, sağlıklı gruptan 20 çocuktan 10'u, primer immün yetmezlik grubundan 16 hastadan 9'u ve kistik fibrozis grubundan 18 hastadan 9'unun ölçek puanı >25 olmuştur. Ancak karşılaştırıldığında gruplar arasında istatistiksel olarak anlamlı fark yoktu (p>0.05). Annelere verilen Beck depresyon ölçek sonuçları gruplar arasında anlamlı farklılık göstermedi (p=0.136). Sonuç: Corona virüs salgını boyunca kliniğimiz pediatrik kistik fibrozis ve primer immün yetmezlik hastalarına bakım sağlamaya devam etti. Aynı tarihler arasında çeşitli şikayetlerle kliniğimize başvuran kronik hastalığı olmayan benzer yaştaki çocuklarla karşılaştırıldığında, tedavi için hastaneye gitmek zorunda kalan kronik hastaların anksiyete düzeylerinin benzer olduğu saptanmıştır.

BACKGROUND:Due to the amazing developments in modulatory treatments, genetic analysis of cystic fibrosis (CF) patients has become even more important. More than 2000 disease-causing variants of the cystic fibrosis transmembrane conductance regulator (CFTR) gene have been found, and their ethnic and geographical distributions vary. We aimed to present the first genetic data from the Southeastern Anatolia region of Turkey and evaluate patients' clinical and genetic characteristics and identify modulatory drugs covering a wider range of mutations by detecting and reporting new mutations. METHODS:Our study included 337 CF patients from three CF reference centers in the Southeastern Anatolia region. RESULTS:Ninety-one distinct mutations and four significant deletions were identified by analyzing CFTR mutations. The most prevalent mutation in our research was F508del (8.92%); the second most prevalent mutation was 2183AA->G, and the third most prevalent mutation was R347P. Additionally, a novel mutation (V1160X) was identified in two siblings. Only 33.5% of our patients qualified for CFTR modulator medication therapy. CONCLUSION:This study elucidates the diverse nature of CFTR mutations in the Turkish population. The heterogenous genetic pool of the Southeastern Anatolia region is more similar to Mesopotamia than to other regions of our country, and receives immigration from the East. Detection and reporting of novel mutations and CFTR mutations that occur at very low frequencies from different populations living in various geographical areas are essential for identifying modulatory medicines that cover a broader range of mutations and also help genetic diagnosis of CF in newborn screening.

Background: Cystic fibrosis-related diabetes (CFRD) is a frequent comorbidity in individuals with cystic fibrosis (CF). While insulin secretion defects are the primary mechanism in CFRD pathophysiology, insulin resistance may contribute as an additional risk factor. Early detection of insulin resistance may help identify patients at higher risk for earlier CFRD development. Objective: The aim of this study was to evaluate the ability of the Matsuda Index to identify insulin resistance in pediatric CF patients and to compare it with HOMA-IR as complementary indicators of glucose metabolism. Methods: In this cross-sectional study, fifty children with CF aged 6–16 years were included. The study involved measuring anthropometric data, fasting insulin, fasting glucose levels, glycated hemoglobin (HbA1c), and C-peptide. An assessment of glucose and insulin levels was performed on the patients through an oral glucose tolerance test (OGTT) at 0, 60, and 120 min. The Matsuda Index was computed, wherein a threshold of ≤4.5 signifies the presence of insulin resistance. Statistical analyses were conducted to compare insulin resistance and sensitivity across groups, using t-tests, correlation, and ANOVA. Results: Among the 50 observed patients, the average Matsuda index score was 17.08 with a standard deviation of 11.16. Eleven individuals (22%) exhibited insulin resistance with a Matsuda Index ≤ 4.5. These patients showed significantly higher insulin levels at 60 and 120 min during the OGTT, with statistically significant p-values of 0.008 and 0.002, respectively. Conclusions: The Matsuda Index may serve as a useful adjunctive tool to help identify insulin resistance in pediatric CF patients, particularly during puberty. Early detection of insulin resistance through the Matsuda Index may facilitate risk stratification and enable timely interventions that could potentially delay the onset or progression of CFRD. However, it should be noted that the ≤4.5 cut-off value was derived from adult studies, and its validity in pediatric CF populations has not been established, which represents a limitation of our finding.

Molecular diagnosis of inborn errors of immunity (IEI) plays a critical role in determining patients' long-term prognosis, treatment options, and genetic counseling. Over the past decade, the broader utilization of next-generation sequencing (NGS) techniques in both research and clinical settings has facilitated the evaluation of a significant proportion of patients for gene variants associated with IEI. In addition to its role in diagnosing known gene defects, the application of high-throughput techniques such as targeted, exome, and genome sequencing has led to the identification of novel disease-causing genes. However, the results obtained from these different methods can vary depending on disease phenotypes or patient characteristics. In this study, we conducted whole-exome sequencing (WES) in a sizable cohort of IEI patients, consisting of 303 individuals from 21 different clinical immunology centers in Türkiye. Our analysis resulted in likely genetic diagnoses for 41.1% of the patients (122 out of 297), revealing 52 novel variants and uncovering potential new IEI genes in six patients. The significance of understanding outcomes across various IEI cohorts cannot be overstated, and we believe that our findings will make a valuable contribution to the existing literature and foster collaborative research between clinicians and basic science researchers.

Objectives Human recombinant enzyme replacement therapy, given to compensate for genetic enzyme deficiency in lysosomal storage diseases, delays the progression of the disease and improves the quality of life. However, enzyme replacement therapy may cause hypersensitivity reactions. Within the scope of this research, we aimed to elucidate the frequency and clinical features of hypersensitivity reactions against enzyme replacement therapy in children with lysosomal storage diseases and clarify the management of these reactions.Methods Medical records of pediatric patients with lysosomal storage disease and receiving enzyme replacement therapy were retrospectively reviewed, and patients who experienced allergic reactions were included in the study. The demographic characteristics of the patients, their diagnosis, the responsible enzyme, the time at which the reaction started and at what dose, the signs and symptoms associated with the reaction, diagnostic tests, the management of the reaction, and the protocol applied for the maintenance of enzyme replacement therapy after the reaction were recorded.Results Hypersensitivity reactions developed in 18 of 71 patients (25.3 %) who received enzyme replacement therapy. The most common cutaneous findings were observed. Anaphylaxis developed in 6 of 18 patients. Patients who experienced recurrent hypersensitivity reactions with premedication or a slower infusion rate, those with positive skin test results, and patients who developed anaphylaxis were given enzyme replacement therapy with desensitization.Conclusions HSR may develop during enzyme replacement therapy, which are vital in lysosomal storage diseases, and discontinuation of enzyme replacement therapy is a significant loss for patients with metabolic disorders. These reactions can be treated with premedication and long-term infusions, but some patients may require desensitization protocols for continued treatment.

IKKα is a multifunctional serine/threonine kinase that controls various biological processes, either dependent on or independent of its kinase activity. However, the importance of the kinase function of IKKα in human physiology remains unknown since no biallelic variants disrupting its kinase activity have been reported. In this study, we present a homozygous germline missense variant in the kinase domain of IKKα, which is present in three children from two Turkish families. This variant, referred to as IKKαG167R, is in the activation segment of the kinase domain and affects the conserved (DF/LG) motif responsible for coordinating magnesium atoms for ATP binding. As a result, IKKαG167R abolishes the kinase activity of IKKα, leading to impaired activation of the non-canonical NF-κB pathway. Patients carrying IKKαG167R exhibit a range of immune system abnormalities, including the absence of secondary lymphoid organs, hypogammaglobulinemia and limited diversity of T and B cell receptors with evidence of autoreactivity. Overall, our findings indicate that, unlike a nonsense IKKα variant that results in early embryonic lethality in humans, the deficiency of IKKα's kinase activity is compatible with human life. However, it significantly disrupts the homeostasis of the immune system, underscoring the essential and non-redundant kinase function of IKKα in humans.

The inducible T-cell costimulator (ICOS) deficiency was first described in 2003. Autosomal re-cessive inherited ICOS deficiency is classified as combined immunodeficiency (CID) and has a wide clinical spectrum including hypogammaglobulinemia, recurrent infections, enteropathies, autoimmunity, lymphoproliferation, and malignancy. WAS/WASL Interacting Protein Family Member 1 (WIPF1) mutation causes WIP deficiency, characterized by thrombocytopenia, immu-nodeficiency, and eczema. Here, we aimed to present a patient with coexisting ICOS and WIP de-ficiency.

OBJECTIVE: Genome-length association studies have shown that Gasdermin B (GSDMB) and Orosomucoid-like 3 (ORMDL3) genes located on the long arm of chromosome 17 are associated with asthma. In this study, it was aimed to determine the possible relationship between asthma control test (ACT), exercise provocation test (ECT), and fractional nitric oxide (FENO) levels and GSDMB and ORMDL3 gene expressions.METHODS: 59 asthmatic and 38 non-asthmatic children were included in the study. We divided the patient group into two subgroups as mild persistent asthma (29 patients) and moderate persistent asthma (30 patients). ORMDL3, GSDMB gene expression levels, ECT, total IgE levels, and eosinophil counts were measured in all cases. In addition, ACT and FeNO levels were measured in children with asthma. Afterward, the relationship of ORMDL3 and GSDMB gene expression coefficient changes with ECT, ACT, and FeNO was examined.RESULTS: When patients with ACT <= 15 were compared with patients with ACT >= 20, ORMDL3 and GSDMB gene expressions were increased 6.74 and 11.74 times, respectively. Comparing patients with ACT >= 20 and ACT <= 15 in terms of coefficient changes (Delta Cq), higher change values were observed for Delta Cq ORMDL3 in patients with ACT <= 15 (p=0.015). Similarly, when patients with FENO <= 25 ppb were compared with patients with FENO >25 ppb, ORMDL3 and GSDMB gene expressions were increased by 2.93 and 3.56 times, respectively. When the coefficient changes were compared, no significant difference was found between FENO <= 25 and FENO >25 patients. There was a slight negative correlation between Delta Cq values and ACT score (p=0.003, r=-0.418 for ORMDL3, and p=0.016, r=-0.345 for GSDMB). In addition, we observed a statistically significant positive correlation between ORMDL3 and GSDMB gene expressions (r=0.80, p<0.001).CONCLUSION: We showed that increased ORMDL3 and GSDMB gene expression levels may be associated with ACT scores, FeNO and ECT in asthma. These findings may encourage future studies with larger numbers of subjects that can use gene expression levels in various asthma phenotypes for prognostic prediction.

Mutations in the SLC29A3 gene cause histiocytosis-lymphadenopathy plus (H) syndrome, a rare autosomal recessive genetic condition that affects numerous systems. We present a 7-year-old Syrian patient with pericardial effusion whose acute phase reactants did not decrease despite treatment. In order to emphasize the variety and raise awareness of H syndrome in the hopes of achieving an early diagnosis and appropriate treatment, molecular investigation of SLC29A3-related disorders is crucial. H syndrome is an uncommon genetic condition with a broad spectrum of phenotypes. Therefore, early genetic testing is essential for the accurate diagnosis of patients. Doctors should be aware of this condition and its symptoms and consider autoimmune diseases as a possible alternative diagnosis in patients with suspected immunodeficiency.

Cystic fibrosis (CF) registries play an essential role in improving disease outcomes of people with CF. This study aimed to evaluate the association of newly established CF registry system in Turkey on follow‐up, clinical, growth, treatment, and complications of people with this disease.

bronchus in bronchoscopy. He explained that he had aspirated while lying down and eating pistachio. Tracheobronchial foreign body aspiration symptoms are not specific, and patients can present with cough, wheezing, shortness of breath, fever, and pneumonia. 3 Organic foreign objects cause more tissue reactions and tend to cause complications like atelectasis and air trapping. 6 Due to progressive inflammation and displacement of the foreign body to the dis-tal airway, they may eventually cause complete obstruction. 7 Mucus plug can cause partial or complete airway obstruction. 8 The incidence of mucus plugs in children without predispos-ing factors is unknown and probably low. 9 Imaging findings of a mucus plug can also mimic a foreign body. 8 In a study conducted on CT findings in 27 children suspected of having foreign bodies, the mucus plug was associated with atelectasis, atelectasis, and pneumonia or pneumonia alone. 10 Since our patient was prone to form a mucus plug due to CF, and imaging findings of the mucus plug could also mimic the foreign body, it was thought that the findings were primarily due to the mucus plug, but when the pistachios were removed by bronchoscopy, it was understood that the infective process had started after pistachios aspiration besides P. aeruginosa pneumonia in our patient.

OBJECTIVE: Several studies have established a relationship between low serum vitamin D levels and the onset of asthma in childhood. In this study, we aim to assess the relationship between vitamin D and asthma. METHODS: This study included 29 mild and 30 moderate persistent asthma and 38 healthy control group. Evaluation of the three groups was carried out in respect of serum vitamin D levels, Respiratory Function Test (RFT), and Exercise Provocation Test (EPT). The two asthma groups were also examined using the Asthma Control Test (ACT) and Nitric Oxide in Exhaled Breath (FeNO) level. RESULTS: The vitamin D levels of the mild and the moderate persistent asthma groups were determined to be lower than the vitamin D levels of the control group (p=0.007). A significant negative correlation was determined in all cases between the vitamin D levels and the broncho-reversibility percentage (p=0.0002). The negative correlation between the vitamin D levels and the broncho-reversibility percentage was more evident in the moderate persistent asthma group (p=0.0001). In the moderate persistent asthma group, a significant positive correlation was determined between the lowness of the maximum forced expiratory volume in EPT and a low vitamin D level (p=0.009). The ACT scores were lower, and the FeNO levels were higher in the moderate asthma group compared to the mild asthma group (p=0.0001). CONCLUSION: The findings showed that low serum vitamin D levels were observed more often in children with asthma, and there was a correlation with increased broncho-reversibility in the RFT and increased bronchial hyper-reactivity in the EPT.

Background: There is conflicting data regarding the role of transforming growth factor-beta 1 (TGF-beta 1) in the pathogenesis of airway hyper-reactivity and asthma exacerbation. Objective: To investigate the role of exhaled-TGF-beta 1 in exercise-induced bronchospasm (EIB) in asthmatic and nonasthmatic healthy children, and in asthma exacerbation and asthma control. Methods: The exhaled-TGF-beta 1 levels of 56 stable asthmatic children and 15 nonasthmatic healthy children were evaluated before and 30 min after an exercise challenge. The exhaled-TGF-beta 1 levels of 20 additional children with asthma exacerbation were evaluated. Results: While no significant difference in the exhaled-TGF-beta 1 levels was found at the baseline, exhaled-TGF-beta 1 levels after the exercise challenge were significantly higher in the non-EIB (n = 31) asthmatics when compared to the asthmatic children with EIB (n = 25) (p = 0.04). Although there was a statistically significant increase in the concentration of the exhaled-TGF-beta 1 after the exercise challenge in the non-EIB asthmatics (p = 0.008), the concentration of the TGF-beta 1 was not increased after the exercise challenge in EIB + asthmatics. The exhaled-TGF-beta 1 was significantly correlated with the ACT score (p = 0.01, r = 0.49) and the baseline FEV1 level (p = 0.02, r = 0.35). The exhaled-TGF-beta 1 levels were significantly higher in the stable asthmatic children when compared to the nonasthmatic children (p < 0.0001). There was no significant difference in exhaled-TGF-beta 1 levels after the exercise challenge in the nonasthmatics. The exhaled-TGF-beta 1 levels were significantly lower in those children with asthma exacerbation when compared to the stable asthmatic children (p = 0.0003). Conclusion: Our results suggest that TGF-beta 1 may play a role in suppressing airway reactivity and its deficiency is associated with asthma exacerbation.

Urticaria (Hives) is a common skin disease which can affect patients' quality of life negatively because of widespread involvement of the body and occasionally a chronic course. In recent years, the popularity of complementary and alternative therapies (TAT) has been increasing in chronic diseases. TAT practices are also increasing in the treatment of allergic/immunologic diseases. Some of these treatments have harmful consequences for patients. In this article, we report a chronic urticaria patient who received traditional cautery therapy implemented with a hot needle and emphasize the harmful effects that alternative treatment methods may cause from time to time.

INTRODUCTION:Hereditary angioedema (HAE) may be fatal and diagnosis can be delayed up to 10 years. We aimed to screen HAE in two villages based on an index case of HAE and to investigate for the mutation of the C1 esterase inhibitor (C1-INH) gene. MATERIAL AND METHODS:A total of 124 people were screened in two villages. The frequency and severity of symptoms were scored. C4, C1-INH levels and C1-INH activity were measured. We investigated for mutations of the C1-INH gene. RESULTS:Thirty-five cases of type I HAE and 7 cases of type II HAE were determined. Thirty-one (73.8%) patients diagnosed with HAE were 18 years old or younger. There was a positive correlation between C4 levels, C1-INH levels (p < 0.0001, r = 0.81), and C1-INH activity levels (p < 0.0001, r = 0.631) and between the age at diagnosis and severity score (p < 0.0001, r = 0.651). A positive correlation was found between the age at first symptom onset and C4 levels (p = 0.002, r = 0.774), and C1-INH levels (p = 0.006, r = 0.714). A marginally significant negative correlation was found between C1-INH activity levels and severity scores (p = 0.1, r = -0.515). We identified a novel heterozygous 1033G>T missense variant of the C1-INH gene, SERPING1, in patients with type I HAE. CONCLUSIONS:There are long delay periods in the diagnosis of HAE and when the index case is present, family screening may be very important and even life-saving, in particular, in paediatric patients without symptoms. Furthermore, the present study provides evidence to link a novel mutation, c.1033G>T, to the development of HAE in a large HAE family from Turkey.

BACKGROUND Hereditary angioedema (HAE) is characterised by recurrent episodes of angioedema and can be fatal. OBJECTIVE The present study aimed to screen HAE. METHODS A total of 60 individuals were screened. The frequency and severity of symptoms were scored from 0 to 8. Measurements were taken of C4 and C1 esterase inhibitor protein (C1-INH) levels. Mutation in the C1 inhibitor gene was examined in 9 patients with HAE. RESULTS A positive correlation between the C1esterase inhibitor proteinlevels and C4 level was detected in the group as a whole (p < 0.001, r = 0.725, n = 60). Anegative correlation between the C1 esterase inhibitor protein level and severity score was observed in the whole group (p < 0.001, r = -0.486, n = 60). A negative correlation was also detected in the entire group between the C4 level and severity score (p = 0.002, r = -0.389, n = 60). In the patients with HAE, a positive correlation between the C1 esterase inhibitor protein level and C4 levels was detected (p = 0.034, r = 0.705, n = 9). A heterozygous c. 601A > T nonsense variant was identified at the C1 esterase inhibitor gene-SERPING1-in patients with Type 1 HAE. CONCLUSION It is well known that there is a prolonged delay in the diagnosis of HAE. The present study demonstrates that it is very important and even life-saving to screen for HAE on the basis of an index case.

Objective Cow’s milk allergy is the most common food allergy in childhood. Changes occur in the protein structure of milk during yogurt fermentation. This study aimed to determine whether children who are diagnosed with a cow’s milk allergy can tolerate yogurt. Methods We performed a yogurt challenge test on 34 children who were diagnosed with a cow’s milk allergy in our Pediatric Allergy Outpatient Clinic. The mean age of 24 male and 10 female children was 24 ± 13 months. Results A reaction was observed in 17 (50%) patients, whereas no reaction was observed in the other 17 (50%) during an oral yogurt challenge test that was performed in all of the 34 patients with a cow’s milk allergy. Cow’s milk-specific immunoglobulin E levels were significantly lower in the group of children who could tolerate yogurt than in the group of children who could not tolerate yogurt. Conclusion Yogurt is tolerated by half of children with a cow’s milk allergy when subjected to a challenge test performed with yogurt, which is consumed as much as milk in Turkey.

BACKGROUND:Corticosteroids are used in the treatment of asthma. The aim of this study was to determine the efficacy of anti-IgE and anti-TNF alpha as asthma treatments. METHODS:A mouse model of chronic asthma was developed. The fluticasone group was exposed to fluticasone and the anti-IgE and anti-TNF groups were administered anti-IgE or anti-TNF. IL-4, and IgE levels were measured, and histological analysis, pathological analysis and miRNA-126, miRNA-133a analyses were applied. RESULTS:The cell concentration in the BAL fluid decreased in all the treatment groups. The rate of perivascular and peribronchial cell infiltration decreased in the lung in the high-dose anti-IgE and anti-TNF groups. Smooth muscle thickness decreased in the lung tissue in the low-dose anti-IgE and anti-TNF groups. Bronchial wall thickness decreased in the lung tissue in the fluticasone+anti-IgE group. The IL-4 level in BAL fluid decreased in the high-dose anti-IgE, fluticasone+anti-IgE and anti-TNF groups. IgE levels increased in the BAL fluid in the high-dose anti-IgE and anti-TNF groups. The lymphocyte level increased in the BAL fluid in the high-dose anti-IgE group. The macrophage level decreased in the BAL fluid in the anti-TNF group. The relative expression of miRNA-126 increased in all groups. The relative expression of miRNA-133a decreased in the placebo and fluticasone groups. The relative expression of miRNA-133a increased in the low-dose anti-IgE, high-dose anti-IgE, fluticasone+anti-IgE and anti-TNF groups. CONCLUSIONS:The results showed that anti-IgE is successful as a treatment. Fluticasone+anti-IgE and anti-TNF were seen to be superior to other therapeutic modalities when used for prophylaxis.