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Objective: The causes of male infertility are heterogeneous but more than 50% of cases have a genetic defect. Chromosomal abnormalities that affect on gametogenesis are one of the principle genetic factors in male infertility. The aim of this study is to determine the frequency and type of chromosomal abnormalities in non-obstructive azoospermic men with severe male factor infertility to give appropriate genetic counseling before assisted reproduction techniques. Materials and Methods: A total of 114 azoospermic infertile males were studied for the cytogenetic evaluation prior to use of assisted reproduction techniques. A detailed history was taken for each man. Karyotyping was performed on peripheral blood lymphocytes according to standard methods. Results: The overall incidence of chromosomal abnormalities was about 22.8% (26/114), including the sex chromosome abnormality 19.3% and the autosomal chromosome abnormality 3.5%. Twenty one of 22 patients with sex chromosome abnormality had classic Klinefelter karyotype. There were 2 mosaic cases involving X and Y chromosomes. Of the four cases with autosomal chromosome anomalies, three cases had balanced reciprocal translocations and one case with inversion. FSH, LH and testosterone levels showed significant increase in azoospermic patients with abnormal karyotype when compared with the normal karyotype (P < 0.05). Conclusions: Our findings are generally in accordance with those from other surveys and confirm that the XXY aneuploidy is the most frequent chromosomal abnormality in azoospermic individuals. The occurrence of chromosomal anomalies among infertile males suggests the need for genetic screening and proper genetic counselling before initiation of assisted reproduction treatment. [ABSTRACT FROM AUTHOR]

Objective: The aim of this study was to investigate the association of the methylenetetrahydrofolate reductase (MTHFR), methionine synthase reductase (MTRR), and methylenetetrahydrofolate dehydrogenase (MTHFD1) polymorphisms in idiopathic infertile men and fertile men. Materials and Methods: Case-control study comprising a total of 233 individuals including 108 idiopathic infertile men with nonobstructive azoospermia and 125 fertile men as control. MTHFR C677T, A1298C; MTRR A66G; and MTHFD1 G19S8A polymorphisms were studied by Real-Time PCR System. The results were analyzed statistically and a P value <. 05 was considered significant. The Chi square test was used to analyze the genotype distributions of polymorphisms. Results: Single-marker analysis revealed that none of the four polymorphisms was significantly associated with nonobstructive azoospermia. All groups were tested for Hardy-Weinberg equilibrium and the deviation from the Hardy-Weinberg equilibrium takes place for MTHFR C677T (P < 0.05) a combination of controls and infertile group. We also performed a multifactor dimensionality reduction (MDR) analysis to investigate any potential epistatic interactions among the four polymorphisms and male infertility. We found a synergistic interaction between some polymorphisms (P < 0.05). Conclusion: Our findings therefore suggest no individual but interactive association between four prominent folate metabolism pathway markers and male infertility among population in the Southeast Turkey. [ABSTRACT FROM AUTHOR]

Abstract Introduction Burned-out testicular tumour is a very rare clinical entity. There is no clinical finding in the testicle, because it regresses spontaneously with no treatment, and generally presents with metastases. Abdominal masses in young male patients may sometimes be caused by a metastatic burned-out testicular tumour. We report a patient with a burned-out testicular tumour that metastasized to retroperitoneal lymph nodes. Case presentation A 28-year-old man complained of an abdominal mass and continuously increasing pain over the previous 2 months. A midabdominal mass, atrophy and minimal induration in the right testis were revealed on physical examination. Ultrasound findings revealed focally increased echogenicity, which is typical of burned-out tumours. Inguinal orchiectomy was performed, and the histological examination of the biopsy specimen revealed a large area of hyalinization, tubular hyalinization, interstitial fibrosis and focal Leydig cell hyperplasia, with no abnormal pathological findings in the epididymis and spermatic cord. The final pathological diagnosis was concluded as "burned-out" testicular tumour. Surgical treatment was followed by appropriate chemotherapy and in the follow-up, the abdominal mass was observed to regress. The patient is currently free of disease 5 years after diagnosis. Conclusion For the detection of intratesticular lesions, especially in patients with extragonadal metastatic involvement and normal palpation findings for the testis, scrotal sonography is very important. A burned-out testicular tumour should be considered and testis biopsies should be performed if there is any risk factor of malignancy.

Allan-Herndon-Dudley syndrome is a neurodevelopmental disorder characterized by motor and intellectual disabilities. Despite its rarity, there has been a rise in interest due to ongoing research and emerging therapy suggestions. In this multicenter, retrospective, cross-sectional study, the genetic characteristics and clinical data of twenty-one cases of genetically confirmed MCT8 deficiency were evaluated. The median age at the diagnosis was 2.4 (1.29; 5.9) years, which ranged from 0.5 to 14.0 years. The median follow-up period was 2.34 years, ranging from four months to 7.9 years. In 21 patients, 17 different variants were detected in the SLC16A2 gene. Eleven of these variants (c.1456delC, c.439G > T, c.949C > A, c.1392dupC, c.1612C > T, c.407dup, c.781del, c.589C > A, c.712G > A, c.311 T > A, c.1461del) have not been previously reported. In this study, with the exception of three cases with fT3/fT4 ratios of 4.95, 3.58, and 4.52, all cases exhibited fT3/fT4 ratios higher than five (9.9 (7.9; 12.0))., Conclusion: MCT8 deficiency is a rare and devastating disorder characterized by central hypothyroidism and peripheral thyrotoxicosis. The fT3/fT4 ratio can be used as a useful diagnostic indicator of MCT8 deficiency in males with mental and motor retardation. There is a need to raise clinicians' awareness of this potentially treatable condition with the emergence of new and promising treatments., What Is Known: • Allan-Herndon-Dudley syndrome, also known as MCT8 deficiency is a rare and devastating disorder characterized by central hypothyroidism and peripheral thyrotoxicosis., What Is New: • In this study, seventeen different variants were detected in the SLC16A2 gene, eleven of which (c.1456delC; c.439G>T; c.949C>A; c.1392dupC; c.1612C>T; c.407dup; c.781del; c.589C>A; c.712G>A; c.311T>A; c.1461del) have not been reported before. • The fT3/fT4 ratio can be used as a useful diagnostic indicator of MCT8 deficiency in males with mental and motor retardation., Competing Interests: Declarations. Ethics approval: The Cumhuriyet University Ethics Committee approved the study protocol (2023–09/23). The principles of the Declaration of Helsinki and Good Clinical Practice for Biomedical Research were followed in conducting the study. Consent to participate: Written informed assent and consent were obtained from all participants and their parents before any procedures. Consent for publication: All authors consent to the publication of the manuscript in EJPE. Competing interests: The authors declare no competing interests., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Introduction: Proportional short stature is one of the most important features of Noonan Syndrome, and adult height often remains below the 3rd percentile. Although the pathophysiology of short stature in NS patients is not fully understood, it has been shown that GH treatment is beneficial in NS, and it significantly improves the height in respect to the results of short and long-term GH treatment., Methods: In this study, the efficacy of GH therapy was evaluated in children and adolescents with Noonan syndrome who attained final height. In this national cohort study, 67 cases with NS who reached final height from 14 centers were evaluated., Results: A total of 53 cases (mean follow-up time 5.6 years) received GH treatment. Height SDS of the subjects who were started on GH tended to be shorter than those who did not receive GH (-3.26± 1.07 vs. -2.53 ±1.23) at initial presentation. The mean final height and final height SDS in girls using GH vs those not using GH were 150.1 cm and -2.17 SD vs 47.4 cm and-2.8 SD, respectively. The mean final height and final height SDS in boys using GH vs. not using GH were 162.48 ± 6.19 cm and -1.81 SD vs 157.46 ± 10.16 cm and -2.68 ± 1.42 SD, respectively. The Δheight SDS value of the cases was significantly higher in the group receiving GH than in those not receiving GH (1.36 ± 1.12 SD vs. -0.2 ± 1.24, p<0.001). Cardiac findings remained stable in two patients with hypertrophic cardiomyopathy who received GH treatment. No significant side effects were observed in the cases during follow-up., Conclusion: In patients with Noonan syndrome who reach their final height, a significant increase in height is observed with GH treatment, and an increase of approximately +1.4 SDS can be achieved. It has been concluded that GH treatment is safe and effective.

Objective: Maturity onset diabetes of the young (MODY) occurs due to mutations in genes involved in pancreatic beta cell function and insulin secretion, has heterogeneous clinical and laboratory features, and account for 1-5% of all diabetes cases. The prevalence and distribution of MODY subtypes vary between countries. The aim of this study was to evaluate the clinical and laboratory characteristics, mutation distribution, and phenotype-genotype relationship in a large case series of pediatric Turkish patients genetically diagnosed with MODY., Methods: MODY cases from 14 different pediatric endocrinology departments were included. Diagnosis, treatment, follow-up data, and results of genetic analysis were evaluated., Results: A total of 224 patients were included, of whom 101 (45%) were female, and the mean age at diagnosis was 9.4±4.1 years. Gene variant distribution was: 146 (65%) GCK; 43 (19%) HNF1A ; 8 (3.6%) HNF4A , 8 (3.6%) KLF11 and 7 (3.1%) HNF1B . The remaining 12 variants were: PDX (n=1), NEUROD1 (n=3), CEL (n=1), INS (n=3), ABCC8 (n= 3) and KJNC11 (n=1). Of the cases, 197 (87.9%) were diagnosed with incidental hyperglycemia, 16 with ketosis (7%) and 7 (3%) with diabetic ketoacidosis (DKA), while 30% presented with classical symptoms of diabetes. Two-hundred (89%) had a family history of diabetes. Anti-GAD antibody was detected in 13 cases, anti-islet antibody in eight and anti-insulin antibody in four. Obesity was present in 16. Distribution of therapy was: 158 (71%) diet only; 23 (11%) intensive insulin treatment; 17 (7.6%) sulfonylureas; 10 (4.5%) metformin; and 6 (2.7%) insulin and oral anti-diabetic treatment., Conclusion: This was the largest genetically diagnosed series from Turkey. The most common gene variants were GCK and HNF1A with much lower proportions for other MODY types. Hyperglycemia was the most common presenting symptom while 11% of patients had diabetes-associated autoantibodies and 7% were obese. The majority of patients received dietary management only., Competing Interests: Conflict of interest: None declared., (©Copyright 2024 by Turkish Society for Pediatric Endocrinology and Diabetes / The Journal of Clinical Research in Pediatric Endocrinology published by Galenos Publishing House.)

Objective: Treatment adherence is crucial for the success of growth hormone (GH) therapy. Reported non-adherence rates in GH treatment have varied widely. Several factors may have an impact on adherence. Apart from these factors, the global impact of the Coronavirus disease-2019 (COVID-19) pandemic, including problems with hospital admission and routine follow-up of patients using GH treatment, may have additionally affected the adherence rate. The primary objective of this study was to investigate adherence to treatment in patients receiving GH. In addition, potential problems with GH treatment during the pandemic were investigated., Methods: This was a multicenter survey study that was sent to pediatric endocrinologists during the pandemic period (June-December 2021). Patient data, diagnosis, history of pituitary surgery, current GH doses, duration of GH therapy, the person administering therapy (either parent/patient), duration of missed doses, reasons for missed doses, as well as problems associated with GH therapy, missed dose data and the causes in the recent year (after the onset of the pandemic) were questioned. Treatment adherence was categorized based on missed dose rates over the past month (0 to 5%, full adherence; 5.1 to 10% moderate adherence; >10% non-adherence)., Results: The study cohort consisted of 427 cases (56.2% male) from thirteen centers. Median age of diagnosis was 8.13 (0.13-16) years. Treatment indications were isolated GH deficiency (61.4%), multiple pituitary hormone deficiency (14%), Turner syndrome (7.5%), idiopathic GH deficiency (7.5%), small for gestational age (2.8%), and “others“ (6.8%). GH therapy was administered by parents in 70% and by patients in 30%. Mean daily dose was 32.3 μg/kg, the annual growth rate was 1.15 standard deviation score (minimum -2.74, maximum 9.3). Overall GH adherence rate was good in 70.3%, moderate in 14.7%, and poor in 15% of the patients. The reasons for non-adherence were mainly due to forgetfulness, being tired, inability to access medication, and/or pen problems. It was noteworthy that there was a negative effect on adherence during the COVID-19 pandemic reported by 22% of patients and the main reasons given were problems obtaining an appointment, taking the medication, and anxiety about going to hospital. There was no difference between genders in the adherence rate. Non-adherence to GH treatment decreased significantly when the patient: administered the treatment; was older; had longer duration of treatment; and during the pandemic. There was a non-significant decrease in annual growth rate as non-adherence rate increased., Conclusion: During the COVID-19 pandemic, the poor adherence rate was 15%, and duration of GH therapy and older age were important factors. There was a negative effect on adherence during the pandemic period., Competing Interests: Conflict of Interest: One author of this article, Feyza Darendeliler, is a member of the Editorial Board of the Journal of Clinical Research in Pediatric Endocrinology. However, she did not take part in any stage of the editorial decision of the manuscript. The editors who evaluated this manuscript are from different institutions. The other authors declared no conflict of interest., (©Copyright 2024 by Turkish Society for Pediatric Endocrinology and Diabetes / The Journal of Clinical Research in Pediatric Endocrinology published by Galenos Publishing House.)

This cross-sectional study examined the effect of sleep disturbance and eating disorders on metabolic control in adolescents with Type 1 Diabetes. The study was conducted with adolescents with T1DM treated at a university hospital in Turkey between October 2023 and January 2024. The study sample consisted of 120 adolescents with T1DM between the ages of 10-18. Data were collected online using the Adolescent Information Form, Dutch Eating Behavior Questionnaire (DEBQ), and DSM-5 Sleep Disorder Scale (SDS). Mean, percentage, and regression analyses were used to analyze the data. Ethics committee, institutional permission and written permission from the adolescents with Type 1 Diabetes and their parents were obtained for the study. In the current study, sleep disturbance and eating disorders explained 38.5% and 40.2% of HbA1c, respectively, and were found to have a significant effect (respectively: F  = 73.737, p  ≤ .001; F  = 19.353, p  ≤ .001). This study provides evidence that eating disorders and sleep disturbance explain approximately half of HbA1c. The results of the study revealed that sleep disturbance and eating disorders were significant predictors of metabolic control in adolescents with type 1 diabetes.

This multi-center point prevalence study evaluated children who were diagnosed as having coronavirus disease 2019 (COVID-19). On February 2nd, 2022, inpatients and outpatients infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) were included in the study from 12 cities and 24 centers in Turkey. Of 8605 patients on February 2nd, 2022, in participating centers, 706 (8.2%) had COVID-19. The median age of the 706 patients was 92.50 months, 53.4% were female, and 76.7% were inpatients. The three most common symptoms of the patients with COVID-19 were fever (56.6%), cough (41.3%), and fatigue (27.5%). The three most common underlying chronic diseases (UCDs) were asthma (3.4%), neurologic disorders (3.3%), and obesity (2.6%). The SARS-CoV-2-related pneumoniae rate was 10.7%. The COVID-19 vaccination rate was 12.5% in all patients. Among patients aged over 12 years with access to the vaccine given by the Republic of Turkey Ministry of Health, the vaccination rate was 38.7%. Patients with UCDs presented with dyspnea and pneumoniae more frequently than those without UCDs (p < 0.001 for both). The rates of fever, diarrhea, and pneumoniae were higher in patients without COVID-19 vaccinations (p = 0.001, p = 0.012, and p = 0.027).  Conclusion: To lessen the effects of the disease, all eligible children should receive the COVID-19 vaccine. The illness may specifically endanger children with UCDs. What is Known: • Children with COVID-19 mainly present with fever and cough, as in adults. • COVID-19 may specifically threaten children with underlying chronic diseases. What is New: • Children with obesity have a higher vaccination rate against COVID-19 than children without obesity. • Among unvaccinated children, fever and pneumoniae might be seen at a higher ratio than among vaccinated children., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: We previously reported that impaired type I IFN activity, due to inborn errors of TLR3- and TLR7-dependent type I interferon (IFN) immunity or to autoantibodies against type I IFN, account for 15-20% of cases of life-threatening COVID-19 in unvaccinated patients. Therefore, the determinants of life-threatening COVID-19 remain to be identified in ~ 80% of cases., Methods: We report here a genome-wide rare variant burden association analysis in 3269 unvaccinated patients with life-threatening COVID-19, and 1373 unvaccinated SARS-CoV-2-infected individuals without pneumonia. Among the 928 patients tested for autoantibodies against type I IFN, a quarter (234) were positive and were excluded., Results: No gene reached genome-wide significance. Under a recessive model, the most significant gene with at-risk variants was TLR7, with an OR of 27.68 (95%CI 1.5-528.7, P = 1.1 × 10 -4 ) for biochemically loss-of-function (bLOF) variants. We replicated the enrichment in rare predicted LOF (pLOF) variants at 13 influenza susceptibility loci involved in TLR3-dependent type I IFN immunity (OR = 3.70[95%CI 1.3-8.2], P = 2.1 × 10 -4 ). This enrichment was further strengthened by (1) adding the recently reported TYK2 and TLR7 COVID-19 loci, particularly under a recessive model (OR = 19.65[95%CI 2.1-2635.4], P = 3.4 × 10 -3 ), and (2) considering as pLOF branchpoint variants with potentially strong impacts on splicing among the 15 loci (OR = 4.40[9%CI 2.3-8.4], P = 7.7 × 10 -8 ). Finally, the patients with pLOF/bLOF variants at these 15 loci were significantly younger (mean age [SD] = 43.3 [20.3] years) than the other patients (56.0 [17.3] years; P = 1.68 × 10 -5 )., Conclusions: Rare variants of TLR3- and TLR7-dependent type I IFN immunity genes can underlie life-threatening COVID-19, particularly with recessive inheritance, in patients under 60 years old., (© 2023. The Author(s).)

Mendelian susceptibility to mycobacterial diseases (MSMD) is a rare primary immune deficiency (PID). IL-12Rβ1 deficiency is the most frequently observed of more than 16 genetic defects that have been identified for MSMD. Genetic and immunological tests are remarkable in the diagnosis of PID. In this study, it was aimed to determine the expression of IFN-γR1 and IL-12Rβ1 in patients with MSMD, their relatives, and healthy individuals and to evaluate the importance of flow cytometry as a fast and reliable method in the diagnosis of MSMD. IFN-γR1 and IL-12Rβ1 expression levels were analyzed in 32 volunteers including six patients, six relatives, and 20 healthy individuals. The normal range of IFN-γR1 and IL-12Rβ1 levels among healthy individuals were determined. IL-12Rβ1 expression level in lymphocytes was found to be low in one patient's relative, and less than 1% in three patients and in one patient's relative. It was observed that the IL-12Rβ1 expression levels of the patient with STAT1 deficiency were increased compared to the healthy individuals. No difference was found in the expression levels of IFN-γR1 and IL-12Rβ1 in one patient, but IFN-γR1 expression was decreased in one patient compared to healthy individuals. Our results show that the determination of IL-12Rβ1 and IFN-γR1 deficiencies by flow cytometry can be used as a rapid and reliable method for the diagnosis of MSMD. The use of this method as a screening test will enable early diagnosis especially in patients whose genetic diagnosis has not been confirmed and clinically compatible with MSMD. In addition, it is thought that IL-12Rβ1 and IFN-γR1 range data obtained from healthy individuals will be considered as a reference source in routine and research studies to be conducted with MSMD.

Testicular adrenal rest tumor (TART) is one of the important complications that can cause infertility in male patients with congenital adrenal hyperplasia (CAH) and should therefore be diagnosed and treated at an early age. The factors that result in TART in CAH have not been completely understood. The aim of this study is to evaluate the genotype-phenotype correlation in CAH patients with TART., Method: Among 230 malepatients with CAH who were followed upwith regular scrotal ultrasonography in 11 different centers in Turkey, 40 patients who developed TARTand whose CAH diagnosis was confirmed by genetic testing were included in this study. Different approaches and methods were used for genotype analysis in this multicenter study. A few centers first screened the patients for the ten most common mutations in CYP21A2 and performed Sanger sequencing for the remaining regions only if these prior results were inconclusive while the majority of the departments adopted Sanger sequencing for the whole coding regions and exon-intron boundaries as the primary molecular diagnostic approach for patients with either CYP21A2 orCYP11B1 deficiency. The age of CAH diagnosis and TART diagnosis, type of CAH, and identified mutations were recorded., Results: TART was detected in 17.4% of the cohort [24 patients with salt-wasting (SW) type, four simple virilizing type, and one with nonclassical type with 21-hydroxylase (CYP21A2) deficiency and 11 patients with 11-beta hydroxylase (CYP11B1) deficiency]. The youngest patients with TART presenting with CYP11B1 and CYP21A2 deficiency were of 2 and 4 years, respectively. Eight different pathogenic variants in CYP21A2were identified. The most common genotypes were c.293-13C>G/c.293-13C>G (31%) followed by c.955C>T/c.955C>T(27.6%) and c.1069C>T/c.1069C>T (17.2%). Seven different pathogenic variants were identified in CYP11B1. The most common mutation in CYP11B1 in our study was c.896T>C (p.Leu299Pro)., Conclusion: We found that 83% TART patients were affected with SW typeCYP21A2 deficiency,and the frequent mutations detected were c.955C>T (p.Gln319Ter), c.293-13C>G in CYP21A2 and c.896T>C (p.Leu299Pro) inCYP11B1. Patients with CYP11B1 deficiency may develop TART at an earlier age. This study that examined the genotype-phenotype correlation in TART may benefit further investigations in larger series., Competing Interests: Declaration of competing interest All authors declare that there is no financial or other potential conflict of interest. All authors declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research reported., (Copyright © 2022 Elsevier Masson SAS. All rights reserved.)

Introduction: Health care workers (HCWs) are disproportionately exposed to infectious diseases and play a role in nosocomial transmission, making them a key demographic for vaccination. HCW vaccination rates are not optimal in many countries; hence, compulsory vaccination policies have been implemented in some countries. Although these policies are effective and necessary under certain conditions, resolving HCWs' hesitancies and misconceptions about vaccines is crucial. HCWs have the advantage of direct contact with patients; hence, they can respond to safety concerns, explain the benefits of vaccination, and counter antivaccine campaigns that escalate during pandemics, as has been observed with COVID-19., Method: A short survey was carried out in May-June 2020 on the vaccination status of HCWs working with pediatric patients with COVID-19. The survey inquired about their vaccination status (mumps/measles/rubella [MMR], varicella, influenza, and diphtheria/tetanus [dT]) and willingness to receive hypothetical future COVID-19 vaccines. The respondents were grouped according to gender, age, occupation, and region., Results: In total, 4927 HCWs responded to the survey. Most were young, healthy adults. The overall vaccination rates were 57.8% for dT in the past 10 years, 44.5% for MMR, 33.2% for varicella, and 13.5% for influenza. Vaccination rates were the highest among physicians. The majority of HCWs (81%) stated that they would be willing to receive COVID-19 vaccines., Conclusion: Although vaccination rates for well-established vaccines were low, a majority of HCWs were willing to receive COVID-19 vaccines when available. Education and administrative trust should be enhanced to increase vaccination rates among HCWs.

Background: We previously reported inborn errors of TLR3- and TLR7-dependent type I interferon (IFN) immunity in 1-5% of unvaccinated patients with life-threatening COVID-19, and auto-antibodies against type I IFN in another 15-20% of cases., Methods: We report here a genome-wide rare variant burden association analysis in 3,269 unvaccinated patients with life-threatening COVID-19 (1,301 previously reported and 1,968 new patients), and 1,373 unvaccinated SARS-CoV-2-infected individuals without pneumonia. A quarter of the patients tested had antibodies against type I IFN (234 of 928) and were excluded from the analysis., Results: No gene reached genome-wide significance. Under a recessive model, the most significant gene with at-risk variants was TLR7 , with an OR of 27.68 (95%CI:1.5-528.7, P= 1.1×10 -4 ), in analyses restricted to biochemically loss-of-function (bLOF) variants. We replicated the enrichment in rare predicted LOF (pLOF) variants at 13 influenza susceptibility loci involved in TLR3-dependent type I IFN immunity (OR=3.70 [95%CI:1.3-8.2], P= 2.1×10 -4 ). Adding the recently reported TYK2 COVID-19 locus strengthened this enrichment, particularly under a recessive model (OR=19.65 [95%CI:2.1-2635.4]; P= 3.4×10 -3 ). When these 14 loci and TLR7 were considered, all individuals hemizygous ( n =20) or homozygous ( n =5) for pLOF or bLOF variants were patients (OR=39.19 [95%CI:5.2-5037.0], P =4.7×10 -7 ), who also showed an enrichment in heterozygous variants (OR=2.36 [95%CI:1.0-5.9], P =0.02). Finally, the patients with pLOF or bLOF variants at these 15 loci were significantly younger (mean age [SD]=43.3 [20.3] years) than the other patients (56.0 [17.3] years; P= 1.68×10 -5 )., Conclusions: Rare variants of TLR3- and TLR7-dependent type I IFN immunity genes can underlie life-threatening COVID-19, particularly with recessive inheritance, in patients under 60 years old.

Dipeptidyl peptidase 9 (DPP9) is a direct inhibitor of NLRP1, but how it affects inflammasome regulation in vivo is not yet established. Here, we report three families with immune-associated defects, poor growth, pancytopenia, and skin pigmentation abnormalities that segregate with biallelic DPP9 rare variants. Using patient-derived primary cells and biochemical assays, these variants were shown to behave as hypomorphic or knockout alleles that failed to repress NLRP1. The removal of a single copy of Nlrp1a/b/c , Asc , Gsdmd , or Il-1r , but not Il-18 , was sufficient to rescue the lethality of Dpp9 mutant neonates in mice. Similarly, dpp9 deficiency was partially rescued by the inactivation of asc , an obligate downstream adapter of the NLRP1 inflammasome, in zebrafish. These experiments suggest that the deleterious consequences of DPP9 deficiency were mostly driven by the aberrant activation of the canonical NLRP1 inflammasome and IL-1β signaling. Collectively, our results delineate a Mendelian disorder of DPP9 deficiency driven by increased NLRP1 activity as demonstrated in patient cells and in two animal models of the disease.

Background: Metabolic syndrome (MetS) and insulin resistance (IR) are known predictors of nonalcoholic fatty liver disease (NAFLD) which is one of the significant comorbidities of obesity. Obese children with MetS and IR are reported to be more likely to have advanced liver fibrosis compared to those without MetS or IR. The aim of this study is to determine the effects of excess weight, MetS and IR on liver fibrosis assessing liver stiffness in children using ultrasound elastography and compare gray scale ultrasonographic findings of hepatic steatosis (HS) with liver fibrosis., Methods: The study group involved 131 overweight/obese children. The control group involved 50 healthy lean children. Groups were adjusted according to body mass index (BMI) and BMI-standard deviation scores (SDS). Liver stiffness measurements which are expressed by shear wave velocity (SWV) were performed for each individual. The study group was further subgrouped as children with MetS and without MetS, with IR and without IR., Results: The mean SWV of liver was 1,07 ± 0,12 m/s in the control group and 1,15 ± 0,51 m/s in the study group. The difference was significant (p=0,047). SWV of liver was weakly correlated with age, BMI, BMI-SDS, Homeostatic Model Assessment-Insulin Resistance and high-density lipoprotein cholesterol. The mean SWV of the liver in the study group for children without MetS was 1,1 ± 0,44 m/s, with MetS was 1,23 ± 0,70 m/s. The difference was not significant (p=0,719). The mean SWV of the liver in the study group for children without IR was 1,02 ± 0,29 m/s, with IR was 1,24 ± 0,61 m/s. The difference was not significant (p=0,101). In multivariate regression analysis, the only independent factor affecting liver stiffness was BMI-SDS (OR:2,584, 95% CI: 1,255- 5,318, p=0,010)., Conclusions: Obesity itself, regardless of MetS or IR seems to be the major problem affecting liver stiffness in this study. However, large scale longitudinal studies might clarify this issue.

Background: Understanding SARS-CoV-2 seroprevalence among health care personnel is important to explore risk factors for transmission, develop elimination strategies and form a view on the necessity and frequency of surveillance in the future., Methods: We enrolled 4927 health care personnel working in pediatric units at 32 hospitals from 7 different regions of Turkey in a study to determine SARS Co-V-2 seroprevalence after the first peak of the COVID-19 pandemic. A point of care serologic lateral flow rapid test kit for immunoglobulin (Ig)M/IgG was used. Seroprevalence and its association with demographic characteristics and possible risk factors were analyzed., Results: SARS-CoV-2 seropositivity prevalence in health care personnel tested was 6.1%. Seropositivity was more common among those who did not universally wear protective masks (10.6% vs 6.1%). Having a COVID-19-positive co-worker increased the likelihood of infection. The least and the most experienced personnel were more likely to be infected. Most of the seropositive health care personnel (68.0%) did not suspect that they had previously had COVID-19., Conclusions: Health surveillance for health care personnel involving routine point-of-care nucleic acid testing and monitoring personal protective equipment adherence are suggested as important strategies to protect health care personnel from COVID-19 and reduce nosocomial SARS-CoV-2 transmission., Competing Interests: Conflict of interest All contributing authors declare no conflict of interest. The study is not funded by any organization. The study is approved by Hacettepe University Ethics Committee (Approval No: 2020/11-57)., (Copyright © 2021 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Objectives: Coronavirus disease 2019 has caused a major epidemic worldwide, and lockdowns became necessary in all countries to prevent its spread. This study aimed to evaluate the effects of staying-at-home practices on the metabolic control of children and adolescents with type 1 diabetes during the pandemic period., Materials and Methods: Eighty-nine patients younger than 18 years old who were diagnosed with type 1 diabetes at least one year before the declaration of the pandemic were included in the study. The last visit data of the patients before and after the declaration of the pandemic, and the frequency of presentation of diabetes-related emergencies from one year after diagnosis of type 1 diabetes to the declaration of the pandemic, and from the declaration of the pandemic to the last visit after the pandemic declaration were compared., Results: The total number of patients was 89, and 48 (53.9%) were boys. The mean (± standard deviation [SD]) age at diagnosis was 8.4 ± 3.7 years (boys 7.9 ± 3.6 years; girls 8.9 ± 3.9 years). There was no statistically significant difference when the SD values of the anthropometric measurements, and the glycosylated hemoglobin (HbA1c) and lipid profile tests were compared. However, the frequency of admission to the emergency service related to diabetes was significantly different., Conclusions: Although the pandemic did not significantly affect the metabolic and glycemic controls of the children with type 1 diabetes included in this study, an increase in the frequency of diabetes-related emergency admissions was noted., (© 2021 Walter de Gruyter GmbH, Berlin/Boston.)

Autosomal inborn errors of type I IFN immunity and autoantibodies against these cytokines underlie at least 10% of critical COVID-19 pneumonia cases. We report very rare, biochemically deleterious X-linked TLR7 variants in 16 unrelated male individuals aged 7 to 71 years (mean: 36.7 years) from a cohort of 1,202 male patients aged 0.5 to 99 years (mean: 52.9 years) with unexplained critical COVID-19 pneumonia. None of the 331 asymptomatically or mildly infected male individuals aged 1.3 to 102 years (mean: 38.7 years) tested carry such TLR7 variants ( p = 3.5 × 10 -5 ). The phenotypes of five hemizygous relatives of index cases infected with SARS-CoV-2 include asymptomatic or mild infection ( n =2, 5 and 38 years), or moderate ( n =1, 5 years), severe ( n =1, 27 years), or critical ( n =1, 29 years) pneumonia. Two boys (aged 7 and 12 years) from a cohort of 262 male patients with severe COVID-19 pneumonia (mean: 51.0 years) are hemizygous for a deleterious TLR7 variant. The cumulative allele frequency for deleterious TLR7 variants in the male general population is < 6.5x10 -4 We also show that blood B cell lines and myeloid cell subsets from the patients do not respond to TLR7 stimulation, a phenotype rescued by wild-type TLR7 The patients' blood plasmacytoid dendritic cells (pDCs) produce low levels of type I IFNs in response to SARS-CoV-2. Overall, X-linked recessive TLR7 deficiency is a highly penetrant genetic etiology of critical COVID-19 pneumonia, in about 1.8% of male patients below the age of 60 years. Human TLR7 and pDCs are essential for protective type I IFN immunity against SARS-CoV-2 in the respiratory tract., (Copyright © 2021, American Association for the Advancement of Science.)

Background: Obesity is a significant public health problem worldwide. Vitamin deficiencies, developing due to monotype nutrition, are more likely to be observed in patients than healthy children. The present study evaluates vitamin and micronutrient levels in children and adolescents with obesity and metabolic syndrome compared to healthy controls., Methods: The study included 73 patients with obesity, 64 patients with metabolic syndrome and 71 healthy children (control group) aged 10 to 16 years. Physical examinations were performed, and waist circumference and systolic blood pressure measurements were recorded. Fasting blood glucose, triglyceride, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, total cholesterol, insulin, vitamin A, vitamin E, vitamin B1, vitamin B2, vitamin B6, vitamin B12, folic acid and free carnitine levels were analyzed. The homeostatic model of assessment-insulin resistance (HOMA-IR) index was calculated and recorded., Results: The mean age of all patients was 11.9±2.6 years. The serum insulin level and HOMA-IR index were found to be significantly higher in the obesity and metabolic syndrome groups. No significant difference was found between the groups in terms of vitamin A, vitamin B6 and free carnitine levels. Significantly decreased vitamin E, vitamin B2, vitamin B12 and folic acid and increased vitamin B1 levels were observed in the obesity and metabolic syndrome groups., Conclusions: Compared to healthy children, children with obesity and metabolic syndrome may have varying degrees of micronutrient and vitamin deficiency due to poor and unbalanced eating habits. These deficiencies should also be considered in the treatment and follow-up of obesity and metabolic syndrome.

This case-controlled study was conducted to determine and compare the emotional eating, social anxiety and parental attitude in those adolescents with obesity and healthy counterparts. The sample of the study consist of obese adolescents in 14-18 aged (n = 150) followed up in the pediatric endocrinology outpatient clinic of a tertiary hospital and healthy adolescents in 14-18 aged (n = 150) who were studying in high schools. The data were collected using a questionnaire form, Emotional Eating Scale Adapted to Use in Children and Adolescents (EES-C), Social Anxiety Scale for Children-Revised (SASC-R) and Parenting Style Scale (PSS). The SASC-R and EES-C mean scores of obese adolescents were 39.03 ± 13.09 (p ≤ 0.001) and 76.66 ± 16.30 (p ≤ 0.001), respectively. The mean scores of PSS-AI, PSS-SS and PSS-PA subscales in obese adolescents were 26.80 ± 4.42 (p ≤ 0.001), 28.14 ± 4.06 (p ≤ 0.001) and 22.32 ± 4.63 (p = 0.037), respectively. There was a low-level correlation between the EES-C and SASC-R mean scores of obese adolescents (p < 0.05). The mean scores of PSS-AI, PSS-SS and PSS-PA subscales of PSS with EES-C and SASC-R of obese adolescents were no correlated (p > 0.05). In this study, the mean scores of the emotional eating and social anxiety of obese adolescents were higher than healthy ones. There was a low level of positive correlation between emotional eating and social anxiety mean scores of obese adolescents., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Objective: We aimed to investigate a possible role of the endocrine disruptors phthalates, di-2-ethylhexyl phthalate (DEHP) and mono (2-ethylhexyl) phthalate (MEHP), in polycystic ovary syndrome (PCOS) aetiopathogenesis. We also wished to evaluate the relationship between phthalates and metabolic disturbances in adolescents with PCOS., Methods: A total of 124 adolescents were included. Serum MEHP and DEHP levels were determined by high-performance liquid chromatography. Insulin resistance was evaluated using homeostasis model assessment-insulin resistance, quantitative Insulin Sensitivity Check Index, fasting glucose/insulin ratio, Matsuda index, and total insulin levels during oral glucose tolerance test. Participants were further subdivided into lean and obese subgroups according to body mass index (BMI)., Results: Sixty-three PCOS and 61 controls, (mean age 15.2±1.5; range: 13-19 years) were enrolled. Serum DEHP and MEHP concentrations were not significantly different between PCOS and control groups. The mean (95% confidence interval) values of DEHP and MEHP were 2.62 (2.50-2.75) μg/mL vs 2.71 (2.52-2.90) μg/mL and 0.23 (0.19-0.29) μg/mL vs 0.36 (0.18-0.54) μg/mL in PCOS and the control groups respectively, p>0.05. Correlation analysis, adjusted for BMI, showed that both phthalates significantly correlated with insulin resistance indices and serum triglycerides in adolescents with PCOS., Conclusion: Serum DEHP and MEHP concentrations were not different between adolescents with or without PCOS. However, these phthalates are associated with metabolic disturbances such as dyslipidemia and insulin resistance, independently of obesity, in girls with PCOS.

Objective: Turkish Directorate of Public Health introduced the first pilot screening program for congenital adrenal hyperplasia (CAH) in four Turkish cities in 2017, and in 2018 extended the program, with a slight change in screening strategy, to fourteen cities. To evaluate the performance of the extended study and update previously reported outcomes., Methods: Retrospective, descriptive study. Neonates of ≥32 gestational weeks and ≥1500 gr birth weight from fourteen cities, born between May-December 2018, were included. Screening protocol included one sample, two-tier testing as applied in the previous pilot study. In the first step, 17α-hydroxyprogesterone (17-OHP) was measured by fluoroimmunoassay in dried blood spots (DBS) obtained at 3-5 days of life. Cases with positive initial screening underwent second tier testing by steroid profiling in DBS using liquid chromatographyt-andem mass spectrometry to measure 17-OHP, 21-deoxycortisol (21-S), cortisol (F), 11-deoxycortisol and androstenedione. The babies with a steroid ratio (21-S+17-OHP)/F of ≥0.7 (increased from ≥0.5 in the earlier pilot study) were referred to pediatric endocrinology clinics for diagnostic assessment., Results: In the evaluated period, 241,083 newborns were screened. 12,321 (5.11%) required second-tier testing and 880 (0.36%) were referred for clinical assessment, twenty of whom were diagnosed with CAH (10 females, 10 males). Sixteen were diagnosed as classical 21-hydroxylase deficiency (21-OHD) CAH (12 with salt-wasting and four with simple virilising CAH), and four cases were identified with 11β-OHD CAH. No case of salt-wasting CAH was missed by neonatal screening (sensitivity was 100%). The incidence of classical 21-OHD and 11β-OHD in the screened population was 1:15,067 and 1:60,270, respectively., Conclusion: Turkish neonatal CAH screening effectively led to earlier diagnosis of 21-OHD and 11β-OHD, using steroid profiling as a second-tier test. This will result in improved care of these patients in the future.

Objective: Hypophosphatemic rickets (HR) is a rare renal phosphate-wasting disorder, which is usually X-linked and is commonly caused by PHEX mutations. The treatment and follow-up of HR is challenging due to imperfect treatment options., Methods: Here we present nationwide initial and follow-up data on HR., Results: From 24 centers, 166 patients were included in the study. Genetic analysis (n=75) showed PHEX mutation in 80% of patients. The mean follow-up period was 6.7±2.4 years. During the first 3-years of treatment (n=91), mild increase in phosphate, decrease in alkaline phosphatase and elevation in parathyroid hormone (PTH) levels were detected. The height standard deviation scores were -2.38, -2.77, -2.72, -2.47 at initial, 1 st , 2 nd and 3 rd year of treatment, respectively (p>0.05). On follow-up 36% of the patients showed complete or significant improvement in leg deformities and these patients had similar phosphate levels at presentation with better levels in 1 st and 2 nd years of treatment; even the treatment doses of phosphate were similar. Furthermore, 27 patients developed nephrocalcinosis (NC), the patients showed no difference in biochemical differences at presentation and follow-up, but 3 rd year PTH was higher. However, higher treatment doses of phosphate and calcitriol were found in the NC group., Conclusion: HR treatment and follow-up is challenging and our results showed higher treatment doses were associated with NC without any change in serum phosphate levels, suggesting that giving higher doses led to increased phosphaturia, probably through stimulation of fibroblast growth factor 23. However, higher calcitriol doses could improve bone deformities. Safer and more efficacious therapies are needed.

Cystic fibrosis (CF) is one of the most common autosomal recessive and multisystemic diseases. CF affects many systems. One of these systems is the endocrine and exocrine functions of the pancreas, causing cystic fibrosis-related diabetes, which is extremely complex and has unique pathogenesis. Maturity-onset diabetes of the young (MODY) is a rare type of diabetes with autosomal dominant inheritance and is not expected in patients with CF. In this study, we present MODY due to a novel glucokinase gene mutation, which is an unexpected form of diabetes in patients with CF. This is previously unreported in the literature., (© 2020 Wiley Periodicals, Inc.)

Background: Tetanus is an infectious disease that can be seen in all age groups in underdeveloped and developing countries, where vaccination programs are inadequate. In developed countries, it is reported more frequently in the adult age group, where the protection of vaccination is diminished and the doses are delayed., Case: In this report, we present generalized tetanus, which was observed in two male patients aged 12 and 6 years, admitted at different times, together with clinical course and treatment approaches. Both patients belong to different nationalities, who immigrated a couple of months before their application to our hospital. They applied with similar histories and complaints and were not vaccinated during infancy., Conclusion: With the development of vaccination programs, this disease with high morbidity and mortality can be prevented.

Objectives: The aim of this study was to determine the level of knowledge of pediatric residents and practicing pediatricians about cow's milk allergy (CMA) and to evaluate the effect of occupational education., Methods: Pediatric residents and pediatricians were included in the study. A survey about CMA was administered to the participants before and after occupational training., Results: A total of 45 doctors were included in the study. Of the group, 31 were pediatric residents and 14 were practicing pediatricians. The pediatric resident group had a mean of 2.3 years professional experience, and the mean was 8.9 years in the pediatrician group. The mean number of correct answers of a possible score of 10 before the training was 8.32±1.37 in the resident group and 7.5±1.69 in the pediatrician group. There was no significant difference between the groups (p=0.09). The mean number of correct answers after training was 10 in the pediatric resident group, and 9.71±0.6 in the pediatrician group. The difference between the groups was statistically significant (p=0.01). Intragroup evaluation post training revealed significantly higher scores (p=0.001)., Conclusion: The results of this study indicate that occupational education significantly increased the level of knowledge about CMA in both pediatric residents and practicing pediatricians., Competing Interests: Conflict of Interest: None declared., (Copyright: © 2019 by The Medical Bulletin of Sisli Etfal Hospital.)

Many transient endocrinologic disorders are frequently seen in newborn period. Early diagnosis and treatment is important for babies. In this article, transient endocrinopathy of newborn and relevant literature were reviewed. Blood sugar problems, especially adrenal insufficiency due to adrenal problems, thyroid problems such as transient hypotirotropinemia, are frequently encountered by physicians. Genital and urinary problems should be evaluated differently according to gender. Problems related to calcium metabolism, problems associated with water metabolism and endocrine skin problems are other problems. It is essential to know the normals of the hormones in the neonatal period in order to recognize them properly, to evaluate them properly and to interpret the tests correctly., Competing Interests: Conflict of Interest: The authors have no conflicts of interest to declare.

Objective: Congenital adrenal hyperplasia (CAH) is the most common form of primary adrenal insufficiency in children. Neonatal screening for CAH is effective in detecting the salt-wasting (SW) form and in reducing mortality. In this study, our aim was to estimate the incidence of CAH in Turkey and to assess the characteristics and efficacy of the adopted newborn CAH screening strategy., Methods: A pilot newborn CAH screening study was carried out under the authority of the Turkish Directorate of Public Health. Newborn babies of ≥32 gestational weeks and ≥1500 gr birth weight from four cities, born between March 27-September 15, 2017 were included in the study. Screening protocol included one sample two-tier testing. In the first step, 17α-hydroxyprogesterone (17-OHP) was measured by fluoroimmunoassay in dried blood spots (DBS) obtained at 3-5 days of life. The cases with positive initial screening were tested by steroid profiling in DBS using a liquid chromatography-tandem mass spectrometry method to measure 17-OHP, 21-deoxycortisol (21-S), cortisol (F), 11-deoxycortisol and androstenedione as a second-tier test. The babies with a steroid ratio (21-S+17-OHP)/F of ≥0.5 were referred to pediatric endocrinology clinics for diagnostic assessment., Results: 38,935 infants were tested, 2265 (5.82%) required second-tier testing and 212 (0.54%) were referred for clinical assessment, six of whom were diagnosed with CAH (four males, two females). Four cases were identified as SW 21-hydroxylase deficiency (21-OHD) (two males, two females). One male baby had simple virilizing 21-OHD and one male baby had 11-OHD CAH. The incidence of classical 21-OHD in the screened population was 1:7,787., Conclusion: The incidence of CAH due to classical 21-OHD is higher in Turkey compared to previous reports. We, therefore, suggest that CAH be added to the newborn screening panel in Turkey. The use of steroid profiling as a second-tier test was found to improve the efficacy of the screening and reduce the number of false-positives.

Hypopituitarism is defined as a decreased release of hypophyseal hormones, which may be caused by disease of the pituitary gland disease or hypothalamus. The clinical findings of neonatal hypopituitarism depend on the causes and on presence and extent of hormonal deficiency. Patients may be asymptomatic or may demonstrate non-specific symptoms, but may still be at risk for development of pituitary hormone deficiency over time. Patient history, physical examination, endocrinological, radiological and genetic evaluations are all important for early diagnosis and treatment. The aim of this paper was to present a review of etiological factors, clinical findings, diagnosis and treatment approaches in neonatal hypopituitarism.

Hyperglycemia has become an important risk factor for mortality and morbidity in the neonatal period, especially with increased survival rates of very low birth weight neonates. Hyperglycemia in the neonatal period develops as a result of various mechanisms including iatrogenic causes, inability to supress hepatic glucose production, insulin resistance or glucose intolerance, specifically in preterm neonates. Initiation of parenteral or enteral feeding in the early period in preterm babies increases insulin production and sensitivity. The plasma glucose is targeted to be kept between 70 and 150 mg/dL in the newborn baby. While a blood glucose value above 150 mg/dL is defined as hyperglycemia, blood glucose values measured with an interval of 4 hours of >180-200 mg/dL and +2 glucosuria require treatment. Although glucose infusion rate is reduced in treatment, use of insulin is recommended, if two blood glucose values measured with an interval of 4 hours are >250 mg/dL and glucosuria is present in two separate urine samples., Competing Interests: Conflict of Interest: No conflict of interest was declared by the authors.

Hypoglycemia is one of the most important and most common metabolic problems of the newborn because it poses a risk of neurological injury, if it is prolonged and recurs. Therefore, newborns who carry a risk of hypoglycemia should be fed immediately after delivery and the blood glucose level should be measured with intervals of 2-3 hours from the 30 th minute after feeding. The threshold value for hypoglycemia is 40 mg/dL for the first 24 hours in symptomatic babies. In asymptomatic babies, this value is considered 25 mg/dL for 0-4 hours, 35 mg/dl for 4-24 hours, 50 mg/dL after 24 hours and 60 mg/dL after 48 hours. Screening should be performed with bed-side test sticks. When values near the limit value are obtained, confirmation with laboratory method should be done and treatment should be initiated, if necessary. The level targeted with treatment is considered 50 mg/dL in the postnatal first 48 hours before feeding, 60 mg/dL after 48 hours in babies with high risk and above 70 mg/dL in babies with permanent hypoglycemia. In cases in which the blood glucose level is below the threshold value and can not be increased by feeding, a glucose infusion of 6-8 mg/kg/min should be initiated. If symptoms accompany, a mini bolus of 10% dextrose (2 ml/kg/min) should accompany. Incements (2 mg/kg/min) should be performed, if the target level can not be achieved and decrements (2 ml/kg/ min) should be performed, if nutrition and stabilization is provided. The infusion should be discontinued, if the infusion rate decreases to 3-5 mg/ kg/min. If necessary, blood samples should be obtained during hypoglycemia in terms of differential diagnosis and the investigation should be performed following a 6-hour fasting period in babies fed enterally and at any time when the plasma glucose is <50 mg/dL in babies receiving parenteral infusion. The hypoglycemic babies in the risk group whose infusions have been terminated can be discharged, if the plasma glucose level is found to be at the target level for two times before feeding and babies with permanent, severe or resistant hypoglycemia can be discharged, if the plasma glucose level is >60 mg/dL following a 6-hour fast., Competing Interests: Conflict of Interest: No conflict of interest was declared by the authors.

Rapid-onset obesity with hypoventilation, hypothalamic dysfunction and autonomic dysregulation (ROHHAD) syndrome is a rare disease that is difficult to diagnosis and distinguish from genetic obesity syndromes. The underlying causes of the disease have not been fully explained. Hypothalamic dysfunction causes endocrine problems, respiratory dysfunction and autonomic alterations. Currently there are around 80 reported patients although this is likely due to underdiagnosis due to lack of recognition. We present two female patients suspected of ROHHAD due to weight gain starting in early childhood. Clinical and biochemical findings such as respiratory and circulatory dysfunction, hypothalamic hypernatremia, central hypothyrodism, hyperprolactinemia and central early puberty in these patients matched the criteria for ROHHAD syndrome. ROHHAD syndrome should be considered in the differential diagnosis of monogenic obesity.

Objective: Insulin is an important hormone for intrauterine growth. Irisin is an effective myokine in the regulation of physiological insulin resistance in pregnancy. Leptin and insulin are associated with fetal growth and fetal adiposity. In this study, we aimed to investigate the relationships between irisin, insulin and leptin levels and maternal weight gain, as well as anthropometric measurements in the newborn., Methods: Eighty-four mothers and newborns were included in the study. Irisin, leptin and insulin levels were measured in the mothers and in cord blood. Anthropometric measurements in the newborn, maternal weight at the beginning of the pregnancy and at delivery were recorded., Results: Birth weight were classified as small for gestational age (SGA), appropriate for gestational age (AGA) and large for gestational age (LGA). There was no difference in irisin levels among the groups. Leptin and insulin levels were found to change significantly according to birth weight (p=0.013, and p=0.012, respectively). There was a negative correlation between the anthropometric measurements of the AGA newborns and irisin levels. This correlation was not observed in SGA and LGA babies. Leptin levels were associated with fetal adiposity., Conclusion: While irisin levels are not affected by weight gain during pregnancy nor by birth weight, they show a relationship with anthropometric measurements in AGA infants. These results may lead to the understanding of metabolic disorders that will occur in later life.

Acute hemorrhagic edema of infancy is a leukocytoclastic small vessel vasculitis of young children that is limited to the skin, generally has a benign course without systemic involvement, and does not require treatment. It is characterized by fever, edema of the lower extremities, and wide purpuric rash of the skin. It typically affects infants aged 6-24 months with a history of recent respiratory system illness. An 11-month-old and a 57-month-old cases with acute hemorrhagic edema of infancy who concurrently have a lower respiratory system infection are presented in this case report., Competing Interests: Conflict of Interest: None declared., (Copyright: © 2018 by The Medical Bulletin of Sisli Etfal Hospital.)

Argun M, Baykan A, Hatipoğlu N, Akın L, Şahin Y, Narin N, Kurtoğlu S. Arrhythmia in thiamine responsive megaloblastic anemia syndrome. Turk J Pediatr 2018; 60: 348-351. Thiamine responsive megaloblastic anemia syndrome (TRMAS) is a rare, autosomal recessive disorder characterized by megaloblastic anemia, diabetes mellitus, and progressive sensorineural deafness. Mutations in the SLC19A2 gene that codes for thiamine transporter 1 protein cause TRMAS, and more than 30 homozygous mutations have been identified to date. Congenital heart diseases and arrhythmias have been reported in few patients. We present cardiac features of five patients with TRMAS. Five patients had macrocytic anemia, diabetes mellitus, and sensorineural deafness. Two siblings had also optic atrophy. SLC19A2 gene mutation was shown in all patients. Two patients developed supraventricular tachycardia during an episode of diabetic ketoacidosis. Five patients had absent P waves on baseline electrocardiography, and one patient had additional low QRS voltage. None of the patients had structural heart disease. Discontinuation of thiamine treatment appears to trigger supraventricular tachycardia episodes at puberty.

Objective: Metabolic impairment in type 1 diabetes mellitus (T1DM) with poor glycemic control causes insulin resistance, non-alcoholic fatty liver disease (NAFLD), atherosclerosis, and increased carotid intima-media thickness (CIMT). Fetuin-A has a protective effect in cardiovascular disorders and is increased in hepatosteatosis. We aimed to investigate the reliability of fetuin-A levels in early detection of diabetic complications in children with T1DM and to identify a cut-off value that may show poor metabolic control., Methods: The study included 80 patients who had T1DM for at least 5 years and who had no chronic complications or an auto-immune disorder. Blood samples were drawn to measure hemoglobin A1c (HbA1c), biochemical parameters, and fetuin-A levels. Anthropometric parameters were also measured. Percent body fat was calculated. Hepatosteatosis and CIMT were assessed by sonography., Results: Mean age of the patients was 13.5 years. Grade 1 hepatosteatosis was detected in 10%. Patients were stratified into 2 groups based on presence of NAFLD. Fetuin-A level was increased in patients with NAFLD. We identified a fetuin-A cut-off value (514.28 ng/mL; sensitivity: 47.34; specificity: 96.72) that may predict NAFLD. HbA1c and total cholesterol levels were found to be higher in patients with fetuin-A levels above higher the cut-off value., Conclusion: Fetuin-A is a reliable parameter in the prediction of complications and poor glycemic control in patients with T1DM.