Diverse Clinical and Immunological Profiles in Patients with IPEX Syndrome: a Multicenter Analysis from Turkey.

PURPOSE: Immunodysregulation, Polyendocrinopathy, Enteropathy, and X-linked syndrome (IPEX), caused by pathogenic FOXP3 variants, is a rare autoimmune disorder with diverse clinical features, including early-onset diabetes, eczema, and enteropathy. Atypical cases show milder symptoms and unique signs, requiring different treatments. Therefore, there are ambiguities in the accurate diagnosis and management of IPEX. We sought to present clinical, genetic, and immunological assessments of 12 IPEX patients with long-term follow-up to facilitate the diagnosis and management of the disease. METHODS: Clinical findings and treatment options of the patients were collected over time. Lymphocyte subpopulations, protein expressions, regulatory T (Treg) and circulating T follicular helper (cTFH) cells, and T-cell proliferation were analyzed. RESULTS: Predominant presentations included autoimmunity (91.6%), failure to thrive (66.7%), and eczema (58.3%). There were four classical and eight atypical IPEX individuals. Allergic manifestations were more common in atypical patients. Notably, chronic diarrhea demonstrated heightened severity compared to other manifestations. Four patients (33.3%) demonstrated eosinophilia, and nine (75%) showed high serum IgE levels. Most patients exhibited normal percentages of Treg cells with reduced CD25, FOXP3, and CTLA-4 expressions, corrected after hematopoietic stem cell transplantation (HSCT). Compared to healthy controls, the TH2-like skewing accompanied by reduced TH17-like responses was observed in cTFH and Treg cells of patients. Overall, nine patients (75%) received immunosuppressants (ISs), and six (50%) underwent HSCT, which was the only treatment revealing sustained control. Sirolimus was used in six patients and showed better control than other ISs. CONCLUSIONS: The first cohort from Turkey with long-term follow-up results, comparing typical and atypical cases, provides insights into the outcomes of different therapeutic modalities and T- cell subtype changes in IPEX syndrome.

Shear Wave Ultrasonographic Elastography in Pediatric Spleens and Its Role in Differential Diagnosis.

Shear wave elastography (SWE) has become popular in clinical practice for many diseases. However, there is not adequate research on spleen-related diseases. This study aimed to investigate the potential of quantitative values obtained through SWE in evaluating spleen pathologies in the pediatric population and to demonstrate its performance to differentiate splenomegaly-related diseases. The research group retrospectively included children with pathological diagnoses related to the spleen from November 2016 to April 2021, and they were categorized into three groups, including portal hypertension (PH), benign lymphoid hyperplasia (BLH), and malignant infiltration (MI). Spleen sizes and parenchymal stiffness were also calculated for each group. Subsequently, mean spleen stiffness in each group was compared with normal values within the same age group. In total, 2781 children (1379 children for the study group; 1402 children for the control group) were enrolled in the study. The highest stiffness was observed in the PH group, which is statistically higher than others (p < 0.05). Although the mean spleen stiffness in the group with BLH was higher than the control and MI group, the difference was not statistically significant (p = 0.08). The mean stiffness in the group with MI was significantly lower than both the control group (p = 0.005) and PH (p = 0.01). In conclusion, using SWE in the differential diagnosis of etiologies causing splenomegaly could make an important contribution.

Assessment of Subclinical Atherosclerosis in Children with Atopic Dermatitis.

INTRODUCTION: Data from studies conducted to date have evaluated clinical atherosclerotic conditions in adult patients with atopic dermatitis (AD). Subclinical atherosclerotic changes that are a precursor of atherosclerotic conditions may begin in childhood. The aim of this study was to investigate the presence of subclinical atherosclerosis in pediatric patients with AD and to determine the associated risk factors. METHODS: A total of 59 patients who were referred to our department over a 6-month period and diagnosed with AD, and 53 healthy controls with a similar age and gender were included in the study. Subclinical atherosclerosis markers (carotid intima media thickness [CIMT], distensibility, stiffness, and strain) were measured using conventional echocardiography. The patients' age, SCORAD index, and duration of symptoms were recorded. Serum total immunoglobulin E, C-reactive protein (CRP), blood lipid profile, and complete blood count markers were measured. RESULTS: The median age of the patients was 61 (10-103) months, and 59.3% of them were male. The patients with AD had a higher CIMT (1.60 ± 0.35 vs. 1.30 ± 0.50 mm) and a lower distensibility (0.006 ± 0.009 vs. 0.01 ± 0.008) and strain (0.10 ± 0.14 vs. 0.19 ± 0.14) than the healthy controls (p < 0.01 for all), but there was no significant difference with regard to stiffness (10.16 ± 21.75 vs. 8.99 ± 12.66). Significant correlations between CIMT and disease duration, age, and the SCORAD index were found (p < 0.01, p < 0.01, and p < 0.05, respectively). No correlation between the subclinical atherosclerosis markers and the other laboratory results was found (p > 0.05 for all). CONCLUSION: This study demonstrates that pediatric patients with AD may express subclinical atherosclerosis markers. The evaluation of subclinical atherosclerosis in these patients revealed that CIMT may be the most important marker, as it displayed positive correlations with symptom duration, age, and disease severity.

Renal involvement, presence of amyloidosis, and genotype-phenotype relationship in pediatric patients with Familial Mediterranean fever: a single center study.

The aim of the study is to investigate how renal involvement is correlated with frequency of amyloidosis, risk factors, and demographic and clinical characteristics in pediatric patients with Familial Mediterranean fever (FMF). Demographic and clinical characteristics and laboratory data of the pediatric patients diagnosed with FMF between 1990 and 2018 were recorded from their files. The diagnosis of patients with amyloidosis (AA) was proven by renal biopsy, and as for patients with non-amyloidosis renal involvement (RI wo AA), amyloidosis could not be detected but they were followed up with the diagnosis of proteinuria and/or hematuria. A total of 1929 FMF pediatric patients were included in the study. About 962 (49.9%) participants were male. There were 134 (6.9%) patients with RI wo AA and 23 (1.2%) patients with AA diagnosed by biopsy. The most common M694V heterozygous/homozygous(het/hom) (31%) mutation was observed. Delay in diagnosis and presence of colchicine resistance were more in patients with RI wo AA and AA (p < 0.05). M694V het/hom mutation was high in both RI wo AA and AA, while the presence of compound heterozygous with M694V mutation was high in RI wo AA (p < 0.01, p = 0.02, p = 0.048, respectively). There was a positive correlation between M694V mutation and monoarthritis/polyarthritis, between compound heterozygous with M694V mutations and presence of chest pain, and between V726A mutation and constipation. Also a negative correlation was found between E148Q and chest pain and between R202Q mutation and monoarthritis/polyarthritis. While M694V mutation increased the risk 2.6 times for AA and 1.7 times for RI wo AA, colchicine resistance increased the risk 33 times for AA and 25 times for RI wo AA.    Concluson: It was concluded in the present study that M694V mutation and colchicine resistance were two important risk factors for RI wo AA (6.9%) and amyloidosis (1.2%) in FMF patients. It should be kept in mind that compound heterozygous with M694V mutations may be associated with chest pain and R202Q mutation may be negatively correlated with arthritis, unlike M694V. The genetic results and clinical findings of the patients should be evaluated together and followed up closely. What is Known: • M694V mutation and colchicine resistance were two important risk factors for RI wo AA and amyloidosis in FMF patients. What is New: • Compound heterozygous with M694V mutations were associated with chest pain and may be more serious than thought. • Another point is that while R202Q mutations were negatively correlated with arthritis, M694V mutations were positively correlated.

The Association of Passive Smoking and Serum Urotensin-II Levels in Children.

Urotensin-II (UT-II) is the most powerful vasoconstrictor agent and is known to play a role in heart failure, diabetes, pulmonary hypertension and asthma. The effect of passive smoking on UT-II levels is unknown. The present study aims to evaluate serum UT-II levels in children exposed to passive smoke. The study included a total of 120 children; 47 children not exposed to passive smoke were included in Group 1 (control group), and 73 children exposed to passive smoke were included in Group 2. Serum samples of the participants were stored at -80 °C after centrifugation and were assessed at least two times with high-precision human ELISA kits. Serum UT-II levels were significantly higher in the children exposed to passive smoke than in the children not exposed. Furthermore, Group 2 was grouped according to the number of cigarettes smoked at home per day, type of passive smoking (second-hand smoke or third-hand smoke), and how many people in their family and/or living together smoked. There was a positive correlation between the number of cigarettes they were exposed to per day and serum UT-II levels. Passive smoking in childhood may be associated with high serum UT-II levels.

Experiences and attitudes of parents of children with cow's milk and other food-allergy.

INTRODUCTION AND OBJECTIVE: The attitude and behaviors of parents are important in the management of children with food allergy (FA). The aim of this study is to evaluate the experiences and attitudes of parents of children with allergy to cow's milk and other FA. MATERIALS AND METHODS: The parents of children with FA were asked to complete an 18-item questionnaire to evaluate the FA history and experiences during diagnosis, treatment, and follow up. RESULTS: The data from 558 (91.2%) survey questionnaire that were filled completely were analyzed. The mean age of the parents was 33.4+4.9. It was found that most common food allergen was cow's milk (85.3%). The mean time to diagnosis from the onset of symptoms was 10.9±18.4 months. Around 229 parents (41.6%) admitted to at least four different physicians and 68 (12.3%) parents admitted to at least five different physicians before diagnosis. The median time to diagnosis from the onset of symptoms was five (1-108) months in the patients admitted to four or more physicians, but it was one (1-48) month in the patients that admitted to less physicians (p˂0.001). The most common symptoms were dermatitis and mucus-bloody stool, the least common ones were cardiovascular symptoms. Only 21.1% of the patients were able to use hypoallergenic formulas (HAF) in accordance with the recommendation of the physician. CONCLUSIONS: Delayed diagnosis of FA is a major concern, and during this period the patients admit many physicians. A majority of the patients with CMPA experience difficulties while using HAFs, and only one-fifth of them is able to use formula regularly.

Parents' views and information status on childhood vaccines: which myths play a role.

OBJECTIVES: The participation of families in childhood vaccination decreases slightly every year around the world. Parents arrive at a decision that vaccines are not safe for their children due to many sources of misinformation. The aim of this study was to investigate the relationship between vaccine hesitancy, vaccine knowledge status and socio-demographic characteristics of the children's parents. METHODS: In this cross-sectional study, 361 parents of children aged 5 years and under, who were admitted to our paediatric outpatient clinic, were included. The parents received scores between 0-20 points according to the correct answers they gave to the questions asked. RESULTS: Although all parents had a positive attitude towards vaccination, some myths, e.g. that vaccination could weaken the child's immune system because it contains heavy metals which could cause infertility and that complementary and alternative medicine could replace vaccination, are thought to be real by 1.7% to 34.6% of the parents. CONCLUSIONS: Since the presence of misinformation may lead to vaccine hesitancy and incomplete vaccination, healthcare personnel have important duties and responsibilities for this group.

Whole exome sequencing identifies a novel variant in ABCA3 in an individual with fatal congenital surfactant protein deficiency.

BACKGROUND: Adenosine triphosphate-binding cassette subfamily A member 3 (ABCA3) gene variants, which cause severe respiratory distress syndrome (RDS) in term newborns, can cause death, especially due to the lack of congenital surfactant protein. The relationship between the types, pathophysiology and effects of ABCA3 gene variants on surfactant metabolism and the clinical phenotype have not yet been fully clarified, but the ABCA3 genotype is known to affect clinical severity. CASE: In our study, in a term newborn with a diagnosis of RDS resulting in death, we detected the c.3677 T > C (p.Leu1226Pro) variant homozygous variant in the ABCA3 gene according to the NM_001089.3 transcript, which, to our knowledge, was identified for the first time in the literature. CONCLUSIONS: We consider that this case report contributes to the literature on RDS by showing the presence of c.3677 T > C (p.Leu1226Pro), a new homozygous variant of ABCA3 in our patient.

Investigation of the serum vitamin D level in infants followed up with the diagnosis of laryngomalacia: a case-control study.

OBJECTIVE: The possible etiological relationship of the vitamin D with laryngomalacia is unclear. The aim of the study was to demonstrate the relationship between laryngomalacia and vitamin D levels. METHODS: Twenty-three non-syndromic babies under the age of 1 year who were diagnosed with laryngomalacia were included in the study group. Forty healthy babies were included in the control group. The detailed anamnesis was obtained and a complete systemic physical examination, a flexible endoscopic laryngeal examination, and laboratory tests [calcium (Ca), phosphorus (P), alkaline phosphatase (ALP), parathormone (PTH), alanine transaminase (ALT), aspartate transaminase (AST), blood urea nitrogen (BUN), creatinine (Cre), and 25-hydroxy vitamin D (25-OH D)] were performed in all patients. All laboratory tests of the groups were compared. RESULTS: It was observed that there was no significant difference in the parameters that could affect vitamin D levels, namely type of feeding, vitamin D supplement intake, and the season when the serum sample was taken (p > 0.05). The vitamin D level was significantly lower (p = 0.003, p < 0.05) and the P and ALP levels were significantly higher (p = 0.016 and p = 0.001, respectively; p < 0.05) in the laryngomalacia group. Although the correlation between vitamin D and PTH was not statistically significant according to the Pearson correlation analysis, it was lower in the laryngomalacia group compared to the control group (p = 0.381, p > 0.05). CONCLUSION: In this study, it was observed that the vitamin D levels were lower in infants with laryngomalacia compared to the control group. We consider that vitamin D deficiency may be a factor in the etiology of laryngomalacia with a yet-to-be-clarified etiology.

The Possible Beneficial Effect of Breastfeeding on the Clinical Course of Urolithiasis Detected During Infancy.

Aim: To evaluate the possible effect of breastfeeding duration on the clinical course and treatment of stones detected during infancy. Materials and Methods: Forty-eight infants with renal stones diagnosed between 0 and 23 months were included in this retrospective cohort study. The children were called for regular follow-up visits for the evaluation of physical examination findings, renal size and parenchymal thickness measured by ultrasonography, localization, size and number of stones, spot urine analysis data, metabolic evaluation findings, and duration of breastfeeding and formula use. The relationship between the disease course (progression or stability) and the duration of breastfeeding were assessed from different aspects by considering the original characteristics of the stones at the time of first diagnosis. Results: The mean follow-up period was 46.21 ± 23.22 months, and the most important metabolic risk factor was hypercalciuria with a rate of 29.2%. The mean duration of breast milk intake was longer in children with no disease progression and in those with a reduced size and/or number of stones. The children receiving only breast milk for the first 6 months of life required treatment less and had less growth retardation. Conclusions: Our findings suggest that breastfeeding has critical effects on infantile urolithiasis. Breastfeeding should be encouraged in children with stones particularly detected during infancy. Further studies with a larger case series are needed to reveal the positive effects of breast milk on the clinical course of urolithiasis in children.

Comparative Effect of Feeding Human Milk as Opposed to Formula on Visual Function and Ocular Anatomy.

Background/Objective: Performance of ocular examinations on children who were breastfed, fed with formula, and combination of the two for the first 6 months of age. Subsequently, refractive errors, allergic conjunctivitis, and retinal nerve fiber layer (RNFL) thickness were evaluated. Materials and Methods: The present study included a total of 242 eyes of 121 children (aged 60-84 months, 65 males, 56 females) admitted to the outpatient clinic of our institution. The patients were divided into three groups according to their feeding pattern during their first 6 months postdelivery: breastfed children (Group 1, n = 40), children fed with a combination of breast and formula milk (Group 2, n = 41), and children exclusively fed with formula-milk (Group 3, n = 40). All patients underwent detailed ophthalmologic examinations, and measurements of the RNFLs were recorded. Results: No significant difference was observed between the groups in terms of refractive error. In Group 3, we found that allergic conjunctivitis was significantly higher than in the other groups. In addition, in Group 3, the thickness of the RNFL was found to be significantly higher in the superior quadrants of both the eyes of children than in Groups 1 and 2 (p < 0.05). Conclusions: We found that the type of feeding experienced by infants in their first 6 months has no effect on refractive error but has significant effects on both allergic conjunctivitis and RNFL. To determine the cause of this difference in the RNFL and to further validate the present study, future studies with larger patient groups and animal experiments are needed.

Omalizumab's role in the treatment of steroid dependent malignant idiopathic anaphylaxis.

If an anaphylaxis episode is not caused by an identifiable trigger, it is defined as idiopathic anaphylaxis. Although it is rarely observed, idiopathic anaphylaxis is clinically significant because of its morbidity and fatality risk. No effective treatment has been demonstrated to date. We report a girl aged 16 years who had had malignant idiopathic anaphylaxis since the age of 12 years who was treated successfully with omalizumab. Although she avoided allergic trigger foods such as tomato and seafood, she used to have these attacks twice a week. Attacks were averted by taking 60 mg prednisone. When prednisone was tapered down to 5 mg on every alternate day, the episodes recurred. Later, attacks could not be controlled on <30 mg of prednisone daily. After being steroid-dependent for 4 years, subcutaneous omalizumab 225 mg every two weeks was started. Under omalizumab therapy, the attacks disappeared and prednisone was discontinued.