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Objective: Diabetic kidney disease (DKD) is influenced by multiple factors, yet its precise progression mechanisms remain largely unclear. This study aimed to create a clinical risk-scoring system based on genetic polymorphisms in the AFF3, CARS, CERS2, ERBB4, GLRA3, RAET1L, TMPO, and ZMIZ1 genes., Methods: The study included a DKD group diagnosed with diabetic kidney disease before age 18 and a WDC group matched by age, gender, and age at diabetes diagnosis. Genetic data and clinical data from diabetes diagnosis to moderately increased albuminuria (MIA) detection were compared between the groups., Results: Among 43 DKD cases, 22 were girls and 21 were boys. At MIA diagnosis, mean body weight SDS was -0.24 ± 0.94, height SDS was 0.34 ± 1.15, and BMI SDS was -0.26 ± 0.94. Systolic blood pressure was at the 72nd percentile (2-99), and diastolic blood pressure was at the 74th percentile (33-99). Significant differences in rs267734, rs267738, and rs942263 polymorphisms were found between DKD and non-complication diabetic groups (13[30.2 %] vs 5[11.6 %], p = 0.034; 14[32.6 %] vs 5[11.6 %], p = 0.019; 26[60.5 %] vs 40[93 %], p < 0.001)., Conclusion: Several factors were identified as significant in DKD onset, including low follow-up weight SDS, elevated diastolic blood pressure, presence of rs267734, and absence of rs942263 polymorphisms. The model demonstrated a specificity of 81.4 % and a sensitivity of 74.4 %., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Ferda Evin reports financial support, article publishing charges, statistical analysis, and writing assistance were provided by Ege University Scientific Research Projects. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

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: 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.)

The study was carried out to determine the psychosocial outcomes of advanced hybrid closed-loop (AHCL) systems in children and adolescents with type 1 diabetes (T1D). Single-center and cohort study with a duration 6 months consisted of 60 children and adolescents with T1D. Standard clinical procedures, including both glycemic indicators, e.g., sensor-measured time within the 70-180 mg/dL range and glycated hemoglobin (HbA1c) levels, and psychosocial metrics were used for data collection. The psychosocial metrics included the Pediatric Quality of Life Inventory (PedsQL) 3.0 Diabetes Module for both children (8-12 years) and parents; the Quality of Life for Youth scale for adolescents (13-18 years); the Strengths and Difficulties Questionnaire (SDQ); the Hypoglycemia Fear Survey for Children (HFS-C); the Revised Child Anxiety and Depression Scale (R-CADS); and AHCLS-specific DTSEQ satisfaction and expectation survey. These metrics were evaluated at the baseline and after 6 months of AHCL use. Of the 60 children and adolescents with T1D for whom the AHCL system was utilized, 41 of them, 23 female and 18 male, completed the surveys. The mean age of the 41 children and adolescents was 12.5 ± 3.2 (min. 6.7, max. 18) years. The time spent within the target glycemic range, i.e., time-in-range (TIR), improved from 76.9 ± 9% at the baseline to 80.4 ± 5% after 6 months of AHCL system use (p = 0.03). Additionally, HbA1c levels reduced from 7.1% ± 0.7% at the baseline to 6.8% ± 0.8% after 6 months of AHCL system use (p = 0.03). The most notable decline in HbA1c was observed in participants with higher baseline HbA1c levels. All patients' HFS-C and AHCL system-specific DTSEQ satisfaction and expectation survey scores were within the normal range at the baseline and remained unchanged during the follow-up period. No significant difference was found in the R-CADS scores of children and adolescents between baseline and after 6 months of AHCL system use. However, there was a significant decrease in the R-CADS scores of the parents. Patients' PedsQL scores were high both at the baseline and after 6 months. The SDQ scores were high at baseline, and there was no significant improvement at the end of 6 months.  Conclusion: This is the first study to investigate in detail the psychosocial outcomes of AHCL system use in T1D patients and their parents. Although state-of-the-art technologies such as AHCL provide patients with more flexibility in their daily lives and information about glucose fluctuations, the AHCL resulted in a TIR above the recommended target range without a change in QOL, HFS-C, SDQ, and R-CADS scores. The scores obtained from the R-CADS conducted by the parents of the children indicated that the use of pumps caused a psychological improvement in the long term, with a significant decrease in the R-CADS scores of the children and adolescents with T1D. What is Known: • Previous studies focused on clinical outcomes of AHCL systems in pediatric T1D patients, showing glycemic control improvements. • Limited attention given to psychosocial outcomes of AHCL systems in children and adolescents with T1D. • Crucial psychosocial factors like quality of life, emotional well-being, and fear of hypoglycemia underexplored in AHCL system context. What is New: • First study to comprehensively examine psychosocial outcomes of AHCL systems in pediatric T1D patients. • Study's robust methodology sets new standard for diabetes technology research and its impact on qualiy of life., (© 2024. The Author(s).)

Introduction: Osteogenesis imperfecta (OI) is a group of phenotypically and genetically heterogeneous connective tissue disorders that share similar skeletal anomalies causing bone fragility and deformation. This study aimed to investigate the molecular genetic etiology and determine the relationship between genotype and phenotype in OI patients with targeted next-generation sequencing (NGS)., Method: In patients with OI, a targeted NGS analysis panel (Illumina TruSight One) containing genes involved in collagen/bone synthesis was performed on the Illumina Nextseq550 platform., Results: Fifty-six patients (female/male: 25/31) from 46 different families were enrolled in the study. Consanguinity between parents was noted in 15 (32.6%) families. Clinically according to Sillence classification; 18(33.1%) patients were considered to type I, 1(1.7%) type II, 26(46.4%) type III and 11(19.6%) type IV. Median body weight was -1.1 (-6.8, - 2.5) SDS, and height was -2.3 (-7.6, - 1.2) SDS. Bone deformity was detected in 30 (53.5%) of the patients, while 31 (55.4%) were evaluated as mobile. Thirty-six (60.7%) patients had blue sclera, 13 (23.2%) had scoliosis, 12 (21.4%) had dentinogenesis imperfecta (DI), and 2 (3.6%) had hearing loss. Disease-causing variants in COL1A1 and COL1A2 genes were found in 24 (52.1%) and 6 (13%) families, respectively. In 8 (17.3%) of the remaining 16 (34.7%) families, the NGS panel revealed disease-causing variants in three different genes (FKBP10, SERPINF1, and P3H1). Nine (23.6%) of the variants detected in all investigated genes were not previously reported in the literature and were classified to be pathogenic according to ACMG guidelines pathogenity scores. In ten (21.7%) families, a disease-related variant was not found in a total of 13 OI genes included in the panel., Conclusion: Genetic etiology was found in 38 (82.6%) of 46 families by targeted NGS analysis. In addition, 9 new variants were assessed in known OI genes which is a significant contribution to the literature.

Objective: The aim of this study is to investigate the molecular genetic causes of non-syndromic primary ovarian insufficiency (POI) cases with the gene panel basedon next generation sequencing analysis and to establish the relationship between genotype and phenotype., Materials and Methods: Twenty three cases aged 14-40 years followed up with POI were included. Patients with a karyotype of 46, XX, primary or secondary amenorrhea before the age of 40, with elevated FSH (>40 IU/mL) and low AMH levels (<0.03 ng/mL) were included in the study. Molecular genetic analyzes were performed by the next generation sequencing analysis method targeted with the TruSight TM Exome panel., Results: Median age of the cases was 17.8 (14.0-24.3) years, and 12 (52%) cases admitted before the age of 18. Fifteen (65%) patients had consanguineous parents. In2 (8.6%) cases, variants detected were in genes that have been previously proven to cause POI. One was homozygous variant in FIGLA gene and the other was homozygous variant in PSMC3IP gene. Heterozygous variants were detected in PROK2, WDR11 and CHD7 associated with hypogonadotropic hypogonadism, but these variants are insufficient to contribute to the POI phenotype., Conclusion: Genetic panels based on next generation sequencing analysis technologies can be used to determine the molecular genetic diagnosis of POI, which has a highly heterogeneous genetic basis.

Objectives: Osteogenesis imperfecta (OI) is a disease caused by defective collagen synthesis. Collagen type 1 is found in many structures in the cardiovascular system. Endothelial dysfunction, which develops prior to the emergence of structural and clinical signs of atherosclerosis, is believed to play a key role in atherogenesis. Endothelial dysfunction may be detected presymptomatically by non-invasive radiologic methods, such as flow-mediated dilatation (FMD) and carotid intima-media thickness (CIMT). These modalities may provide early indicators of endothelial dysfunction. This cross-sectional comparative study aimed to investigate early-stage radiological markers of endothelial dysfunction and cardiovascular diseases in OI patients and healthy controls and to investigate the correlation of findings with OI genotype., Methods: Thirty patients diagnosed with OI were paired with thirty healthy age- and gender-matched controls and echocardiogram findings were compared., Results: None of the patients had known underlying cardiovascular disease. The mean age was 13.18 ± 2.91 years. According to Sillence classification, 15 patients had type 1 OI, 10 had type III, and 5 had type IV. Mean CIMT in the OI group was higher in the control group (OI group: 0.42 ± 0.06 vs. healthy controls: 0.34 ± 0.04 mm, p<0.01), and mean FMD percent was lower in the patient group (p<0.01). Left ventricular ejection fraction was 78.97 ± 10.32 vs. 77.56 ± 8.50 %, (OI group: 7.00 ± 3.06 vs. healthy controls: 12.14 ± 1.99, p=0.56), and fractional shortening was 42.68 ± 11.94 vs. 40.23 ± 7.99 %, (p=0.35), in OI patients and controls, respectively., Conclusions: Pediatric patients with OI without clinical signs of cardiovascular abnormality had significantly worse CIMT and FMD findings than healthy controls. However, no difference was determined when comparing left ventricular ejection fraction or fractional shortening. OI patients may need to be screened for cardiovascular system complications starting from an early age., (© 2023 Walter de Gruyter GmbH, Berlin/Boston.)

Objective: Diabetic ketoacidosis (DKA) is a life-threatening, acute complication of type 1 diabetes mellitus (T1DM). Infection is the most common precipitating factor for DKA, being responsible for more than 50% of such complications. The frequency and severity of DKA in children with T1DM, before and during the coronavirus disease 2019 outbreak were evaluated and compared with pre-pandemic presentation and severity rates., Methods: In total, 199 patients younger than 18 years were included in the study. Patients were divided into two groups: the Coronavirus disease-2019 (COVID-19) pandemic group (new onset T1DM presenting from March 2020 to March 2021; the control group included new onset T1DM from March 2016 to March 2020., Results: The rate of DKA at presentation was similar (p=0.393) during the pandemic period (58.3%) compared to the pre-pandemic years (44.8-64.3%). Although the percentage of DKA was similar, the rate of severe DKA in the COVID-19 group was higher than previous years. Although not significant, the duration of diabetes symptoms was longer in the COVID-19 period than the previous years., Conclusion: This study suggests that the rate of severe DKA, but not the overall rate of DKA, has increased during the COVID-19 pandemic compared to the prior four years. This may be due to the behavior of the parents of sick children and the limited access to the healthcare system. Despite this limited access, parental concern may have been sufficiently high to seek medical attention for their children, avoiding an increased frequency of DKA as the first presentation of new-onset T1DM.

Objective: This aim of this study was to investigate the effect of additional insulin dosing for high fat/high energy density mixed meal over 12 hours., Methods: In this single-center, non-blinded, randomized, cross-over study, a high fat/high energy density test meal was used to study the impact on glycemic response of either carbohydrate counting (CC) on the first day and the Pańkowska algorithm (PA) on the second test day. The two methods were compared in 20 adolescents with type 1 diabetes (T1D), aged 9-18 years, using insulin pump therapy and continuous glucose monitoring on postprandial early (0-120 min), late (120-720 min), and total (0-720 min) glycemic response., Results: There was no difference between groups in the duration of normoglycemia in the early period. Postprandially, 50% of patients developed hypoglycemia using the PA at a median of 6.3 (5.6-7.9) hours and the PA was subsequently modified for the remaining ten patients. Area under the curve (AUC) for the early period decreased non-significantly in the CC group, indicating less normoglycemia. No significant difference was found in the AUC of the PA (no hypoglycemia n=4) and modified PA groups (no hypoglycemia n=6) over the whole period (0-12 hours). AUC for level 2 hyperglycemia was statistically greater in the PA-no hypoglycemia patients compared to modified PA-no hypoglycemia patients., Conclusion: There were inter-individual differences in glycemic response to high fat/high energy density meals. An individualized approach to insulin dosing by evaluating food diary and postprandial glucose monitoring appears to be optimal for children and adolescents with T1D., (©Copyright 2023 by Turkish Society for Pediatric Endocrinology and Diabetes | The Journal of Clinical Research in Pediatric Endocrinology published by Galenos Publishing House.)

Objectives: Neurocognitive functions of children with type 1 diabetes mellitus (T1D) are reported to be poorer than those of healthy peers. The aim was to investigate the effects of age of onset of diabetes, metabolic control, and type of insulin regimen on neurocognitive functions in children and adolescents with T1D., Methods: Forty-seven children aged 6-18 years, with T1D for at least five years, were included. Children with a known psychiatric disorder or chronic diseases other than T1D were excluded. Intelligence via the Wechsler children's intelligence scale (WISC-R), short-term memory via the audio-auditory digits form B (GISD-B) test, visual motor perception via the Bender Gestalt test, and attention via the Moxo continuous attention and performance test, timing, hyperactivity, and impulsivity (Moxo-dCPT) were assessed., Results: Compared with the T1D group, healthy controls had higher scores in terms of verbal intelligence quotient (IQ), performance IQ, and total IQ mean scores on WISC-R (p=0.01, p=0.05 and p=0.01, respectively). On the MOXO-dCPT test, the T1D group had higher impulsivity compared to the control group (p=0.04). Verbal IQ was better in the moderate control group than in the poorer metabolic control (p=0.01). Patients with no history of diabetic ketoacidosis (DKA) had higher performance, verbal and total intelligence scores than the group with history of DKA., Conclusions: Poor metabolic control and a history of DKA in children with T1D adversely affected neurocognitive functions. It would be beneficial to consider the assessment of neurocognitive functions in T1D and to take the necessary precautions in follow-up., (© 2023 Walter de Gruyter GmbH, Berlin/Boston.)

Background: Administration of insulin may be associated with substantial cutaneous adverse effects, such as lipoatrophy and lipohypertrophy (LH), which can cause glycemic excursions above and below the target levels for blood glucose. Our aim was to evaluate the effect on compliance with the use of insulin administration site, dermatological complications and diabetes management in children with type 1 diabetes (T1D)., Methods: Patients aged 0 - 21 years who were followed up with the diagnosis of T1D for at least one year were included. A 14-question survey including demographic characteristics and a subjective opinion of skin-related complications of insulin administration was given. Data were obtained from the medical records to evaluate the effect of dermatological complications on diabetes management. This study was checked with the STROBE checklist., Results: Two hundred and fifty-four patients were included and 53% of these were female. The mean age was 14.9 ± 4.7 years and the duration of T1D was 7.3 ± 4.1 years. The mean HbA1c level was 8 ± 1.4% and the mean total insulin dose was 0.84 ± 0.25 units/kg/day. More than half of the individuals (57%) were receiving multiple daily injections (MDI) and 43% were on insulin pump therapy (IPT). Of the participants, 11.8% reported LH, 7.5% wound, 21.7% allergy, 55.5% bleeding, 41.3% bruising and 47.2% pain. LH rates varied significantly by regimen, 17.1% in MDI and 4.6% with IPT (p = .001). Those with LH were using higher median doses of insulin (0.97 U/kg/day) than those who did not (0.78 U/kg/day; p = .016). LH was reported more frequently (18.3%) in patients with frequent hypoglycemia (p = .007). Positive correlation between BMI-SDS and LH in patients aged <18 years was found (p = .043). LH rates by site were: right arm 20.8%, left arm 26.4%, right abdomen 26.4%, left abdomen 22.6% and 1% in the right and left leg., Conclusions: Local complications of insulin therapy are common in young patients with T1D. The complication with the most impact on metabolic control was LH, present in nearly 12% of patients. Users of IPT have a significantly lower risk of LH. The results emphasise the importance of individualised education for young T1D patients and their families about injection site preference and rotation techniques., Relevance to Clinical Practice: The diabetes team should check the insulin administration sites of children with type 1 diabetes at each visit and provide repeated education about the dermatological complications of insulin., (© 2021 John Wiley & Sons Ltd.)

The novel coronavirus disease (COVID-19) has emerged as a global pandemic. This was a prospective, case-control study conducted in Izmir, Turkey. The aim of this study was to assess the relationship between COVID-19 and new-onset T1DM. We included pediatric patients (aged 6 mo-18 yr) with new-onset type-1 diabetes mellitus (T1DM) diagnosed during the COVID-19 pandemic, between April 2020 and January 2021. Polymerase chain reaction was used to diagnose COVID-19 after hospital admission. An enzyme-linked immunoassay for IgM and IgG against SARS-CoV-2 was performed after the diagnosis was confirmed. In the control group, the blood antibody test was conducted as close as possible to the time of the T1DM patient referral. A total of 118 participants were included in the study, comprising 57 (48%) patients with new-onset T1DM and 61 (52%) healthy controls. Of the 57 patients, 36 (63.2%) presented with DKA, 17 (29.7%) with diabetic ketosis, and four (7%) incidentally. The SARS-CoV-2 antibody test was positive in five (8.7%) patients with T1DM and six (10%) controls. The rate of positivity did not differ between the two groups (p = 0.901). It was not possible to demonstrate a clear association between SARS-CoV-2 infection and new-onset T1DM. Whether SARS-CoV-2 increases susceptibility to diabetes by triggering islet cell autoimmunity and affects the timing of overt diabetes in patients with existing autoimmunity should be studied in large cohorts., Competing Interests: None of the authors have any potential conflicts of interest associated with this research., (2022©The Japanese Society for Pediatric Endocrinology.)

The current Coronavirus disease-2019 (COVID-19) pandemic has forced health care teams to look for alternative approaches to manage a great number of children with diabetes, not only in rural but also in urban locations. The aim was to assess the provision of information about follow-up of new-onset pediatric type 1 diabetes (T1D) patients, and to investigate the integration of telemedicine into routine clinical care in the long term. The changes in coefficient of variation (CV), standard deviation and percentages of time in range (TIR), time below range (TBR) and time above range were evaluated in eight children with new-onset T1D, diagnosed during the COVID-19 pandemic. The study period was two-months of follow-up using a telemedicine system. Median follow-up time was 51 (24-66) days. Two of the patients were using low glucose suspend system and six were on multiple daily injection therapy. Target TIR values were achieved in seven patients in the last televisit and, in line with recent guidelines, a TBR <70 mg/dL (<3.9 mmol/L) (level 1 hypoglycemia) of <4% and a TBR <54 mg/dL (<3.0 mmol/L) (level 2 hypoglycemia) of <1% were achieved in all patients. Seven patients achieved a CV of <36% at their last televisit. Telemedicine as an alternative follow-up tool during unusual circumstances such pandemics, even in countries where it is not routinely used, could be beneficial to achieve optimum glycemic control in patients with new-onset T1D.

Objective: Monogenic diabetes is a heterogeneous disease that causes functional problems in pancreatic beta cells and hyperglycemia. The aim of this study was to determine the clinical and laboratory features, the admission characteristics and distribution of monogenic form of diabetes in childhood in Turkey., Methods: Patients aged 0-18 years, who were molecularly diagnosed with monogenic diabetes, and consented to participate, were included in the study., Results: Seventy-seven (45.6%) female and 92 male cases with a mean age of 8.18±5.05 years at diagnosis were included. 52.7% of the cases were diagnosed with monogenic diabetes by random blood glucose measurement. The reason for genetic analysis in 95 (56.2%) of cases was having a family member diagnosed with diabetes under the age of 25. At the time of diagnosis, ketone was detected in urine in 16.6% of the cases. Mean hemoglobin A1c on admission, fasting blood glucose, fasting insulin, and c-peptide values were 7.3±2.1%, 184.9±128.9 mg/dL, 9.4±22.9 IU/L, 1.36±1.1 and ng/L respectively. GCK-MODY was found in 100 (59.2%), HNF1A-MODY in 31 (18.3%), and variants in ABCC8 in 6 (3.6%), KCNJ11 in 5 (3%), HNF4A in 2 (1.2%), and HNF1B in 2 (1.2%)., Conclusion: Recent studies have indicated HNF1A-MODY is the most frequent of all the MODY-monogenic diabetes cases in the literature (50%), while GCK-MODY is the second most frequent (32%). In contrast to these reports, in our study, the most common form was GCK-MODY while less than 20% of cases were diagnosed with HNF1A-MODY.

Objective: Pump-treated children with type 1 diabetes (T1DM) have widely differing basal insulin (BI) infusion profiles for specific periods of the day. The pattern of BI requirements depends on the timing and magnitude of cortisol and growth hormone secretion within each age group. In adolescents and young adults, a decreased insulin sensitivity is seen, particularly in the early morning (dawn phenomenon) and to a lesser extent, in the late afternoon (dusk phenomenon). Different approaches exist for the inititation of basal rates. However, there is a lack of evidence-based recommendation, especially in young children. Usually the basal rates are set equally throughout day and night or the day is divided into tertiles. The aim of this study was to analyze the change of the initial, equally distributed, BI rates over the first year of standard insulin pump therapy., Methods: A total of 154 patients with T1DM, aged between 0 and <21 years at diagnosis, from a single center were documented. Patients were divided into five age groups according to age at pump initiation: group 1, <5 years (n=36); group 2, 5-8 years (n=20); group 3, 8-15 years (n=74); group 4, 15-18 years, (n=19); and group 5, >18 years, (n=5). Distribution of hourly basal rates at the initiation of the pump and at the end of first year were evaluated., Results: Median (range) age and diabetes duration was 14.46 (1.91-26.15) and 7.89 (1.16-17.15) years, respectively. Forty-four percent were male, 56% were female. Mean total insulin dose/kg in the whole cohort at the initiation and after one year of pump therapy was 0.86±0.23 U/kg and 0.78±0.19 U/kg, respectively and differed significantly between each age group (p<0.001; p<0.001). Mean daily basal rate/kg showed significant differences between the five groups (p<0.001). Circadian distribution of BI differed markedly among the five age groups., Conclusion: At the initiation of insulin pump therapy, circadian profiles by age group should be taken into account in pediatric patients to optimize basal rate faster and more easily.

Introduction: Disorders of sex development (DSD) constitutes a group of congenital conditions that affect urogenital differentiation and are associated with chromosomal, gonadal and phenotypic sex abnormalities., Objective: To evaluate the clinical and genetic features of childhood DSD cases., Materials and Methods: DSD patients followed up between the years of 2002-2018 were evaluated in terms of their complaints, demographic, clinical features and genetic diagnoses., Results: Out of 289 patients, 143(49.5%) were classified as 46XY DSD, 62(21.5%) as 46XX DSD and 84(29%) as sex chromosomal DSD. Genetic diagnosis was achieved in 150 patients (51.9%). The distribution of the molecular diagnosis of the 46XY DSD patients were; 12 (26.6%) SRD5A2, 10 (22.2%) AR, 7 (15.5%) HSD17B3, 3 (6.6%) WT-1, 2 (4.4%) AMHR2, 2 (4.4%) AMH, 2 (4.4%) LHCGR, 2 (4.4%) HSD3B2, 1 (2.2%) NR5A1, 1 (2.2%) CYP17A1 and 1 (2.2%) SRY mutation. Fifty (80.6%) of the 46XX DSD patients received a diagnosis with clinical and laboratory findings. Twenty-four (38.7%) of them were 21-hydroxylase deficiency, 9(14.5%) Rokitansky-Küster-Hauser Syndrome, 4 (6.5%) 11-β hydroxylase deficiency, 3 (4.8%) gonadal dysgenesis and 2 (3.2%) aromatase deficiency. In 46XX group pathogenic mutations were detected in 21(33.8%) of the patients. Eighty-four (29%) patients were diagnosed as sex chromosomal disorder. Of these 66 (78.5%) were Turner Syndrome, 6 (7.2%) Klinefelter Syndrome and 10 (11.9%) mix gonadal dysgenesis. Gender re-assignment was decided in 11 patients. Malignant and pre-invasive lesions was diagnosed in 8 (2.7%) patients., Conclusion: Many of DSD's are clinically similar and etiology of numerous of them still cannot be established. A multi-disciplinary approach and new rapid genetic diagnostic methods are needed in the process from diagnosis to gender assignment and follow-up., (Copyright © 2021 Elsevier Masson SAS. All rights reserved.)

Objective: The aim of this study was to assess the quality of life (QoL) and psychological well-being in child and adolescent with disorders of sex development (DSD)., Methods: Sixty-two cases, aged 2-18 years, who were followed by a multidisciplinary DSD team were included. All participants and their parents were requested the complete the Pediatric Quality Of Life Inventory (PedsQL) and the Strengths and Difficulties Questionnaire. The psychiatric diagnoses of the patients were evaluated according to Schedule for Affective Disorders and Schizophrenia for School-Age Children/Present and Lifetime Turkish Version., Results: There was no significant difference between the 46,XX DSD and 46,XY DSD groups for both child and parent in Total PedsQL score. In the subscale scores, the PedsQL Physical Functionality Score reported by children was significantly lower for the 46,XX DSD group than for the 46,XY DSD group (p=0.01). There was a psychiatric diagnosis in 25.8% of cases. The PedsQL School Functionality Score reported by children in the group with psychiatric diagnosis was significantly lower than the group without psychiatric diagnosis (p=0.018). In the group with psychiatric diagnosis, the PedsQL Total Score and the subscale scores (Emotional Functionality Score, Social Functionality Score, School Functionality) reported by parents were significantly lower than in parents of the group without psychiatric diagnosis., Conclusion: This study emphasized that psychiatric disorders in DSD patients negatively affect the QoL. Psychiatric support and counseling from a multidisciplinary team are very important for families affected by DSD.

Objectives: This study aimed to determine the effects of continuous subcutaneous insulin infusion (CSII) treatment on anthropometric measurements, mean HbA1c, and insulin dosage in patients diagnosed under 5 years of age and compare with multiple-dose injection therapy (MDI)., Methods: Children with type 1 diabetes mellitus, diagnosed <5 years since 2000 and their 19-year follow-up were evaluated retrospectively. Weight, height, body mass index (BMI), blood pressure, and HbA1c values were recorded for each visit., Results: Hundred and five patients (58.1% female, 41.9% male) were included in the study. Sixty-three (60 %) patients were treated by CSII and 42 (40%) by MDI. Mean age at diagnosis was 2.68 ± 1.42 and 3.29 ± 1.30 years respectively. Mean follow-up was 7.42 ± 4.76 and 6.01 ± 4.41 years respectively. For each group, weight standard deviation score (SDS) increased significantly in the first year after the diagnosis (p<0.001), and with the onset of puberty weight SDS decreased significantly (p<0.001). The trend of weight and BMI SDS changes over the years showed similar characteristics in both groups. During follow-up height SDS was similar in both groups except in Tanner stage 5. When puberty was completed, mean height SDS was 0.51 ± 1.03 in CSII and -0.31 ± 0.75 in the MDI group (p: 0.029). Mean HbA1c was significantly lower in the CSII group (7.62 ± 0.82 and 8.17 ± 1.22 respectively). Systolic and diastolic blood pressure change trends during the follow-up were also similar in both groups., Conclusions: CSII treatment had positive effects on metabolic control and height SDS in patients with early-onset diabetes without increasing BMI., (© 2020 Aysun Ata et al., published by De Gruyter, Berlin/Boston.)

Objectives: Glycated hemoglobin (HbA1c) has proven to be indicative in the development of microvascular complications. In this study, the contribution of HbA1c variability to microvascular complications was evaluated., Methods: Twenty-one cases with type 1 diabetes mellitus (T1DM) who developed microvascular complications and 39 cases without complications, that were similar in terms of gender, age of diagnosis, insulin treatment, insulin doses (U/kg), and mean HbA1c levels were included., Results: Mean age of T1DM diagnosis was 5.87 ± 3.93 years in the complication group and 4.63 ± 3.33 years in the control group. Nephropathy was detected in 17 cases, neuropathy in 8 cases, and retinopathy in 1 case. Nephropathy occurred at a mean age of 11.52 ± 4.12 years and neuropathy at 14.13 ± 5.68 years. The mean HbA1c during follow-up was similar in the group with complications and the control group (8.60 ± 0.63 vs. 8.84 ± 1.32). Adjusted HbA1c-standard deviation (SD) and HbA1c-variation coefficient (CV) values were 1.30 ± 0.65 and 14.36 ± 6.23 in the group with complications (p=0.014), and 0.91 ± 0.37 and 10.59 ± 4.01 in the control group (p=0.013). In the Receiver Operating Characteristic (ROC)-analysis for microvascular complications, the limit value HbA1c-CV was 11.99 (sensitivity: 61.9%, specificity: 71.9%). This value for HbA1c-SD was 0.9699 (sensitivity: 71.43%, specificity: 66.67%)., Conclusions: This study has shown that long-term fluctuations in HbA1c are associated with the development of microvascular complications in type 1 diabetes., (© 2020 Walter de Gruyter GmbH, Berlin/Boston.)

Melanocortin 4 receptor gene plays an important role in food intake, energy balance, and weight control. The autosomal dominantly inherited MC4R variants cause obesity by causing hyperphagia and decreased sense of satiety. Homozygous variants are rarely reported, and they cause earlier/severe obesity. Our objective is to determine the MC4R gene variant frequency in children and adolescents with familial early-onset obesity. One hundred thirty-nine children and adolescents (57 girls/82 boys) whose weight increase started before the age of 5 years and who had early-onset obesity in at least one of their first-degree relatives were included in the study. Obesity is defined as body mass index (BMI) of ≥ 95th percentile, and as extreme obesity is defined if the BMI ≥ 120% of the 95th percentile or ≥ 35 kg/m 2 . Children having genetic syndromes associated with obesity and mental retardation or taking drugs that promote changes in eating behavior or weight were excluded from the study. Coding region of the MC4R gene was sequenced by using the Illumina MiSeq Next Generation Sequencing System. The mean age of the patients was 7.3 ± 3.7 years, and the mean BMI SDS was 3.7 ± 0.7. While 118 patients (85%) were prepubertal, 21 patients (15%) were pubertal. Seven different variants were identified in 12 patients by giving a variant detection rate of 8.6%, of these five were previously identified missense variants p.N274S, p.S136F, p.V166I, p.R165W, and p.I291SfsX10. One homozygous variant p.I291SfsX10 (c.870delG) was detected in a severely obese 2-year-old boy, and other variants were heterozygous. Two novel variants were found: p.M200del and p.S188L. By using the in silico analysis software, these novel variants were predicted to be disease causing.Conclusion: MC4R gene variants are quite common in childhood obesity in Turkish population. Screening the variants in MC4R gene is necessary in patients with severe childhood-onset obesity. In such patients, comorbidities of obesity can be seen from early years. What is known • The frequency of MC4R mutations in obese patients was approximately 0-6.3%. What is new • In obese Turkish pediatric population, unlike other European countries, MC4R gene variants are quite common as we found a variant rate of 8.6% • We believe it is necessary to screen the variants in MC4R gene in patients with severe childhood-onset obesity and who had early-onset obesity in at least one of their first-degree relatives in Turkish population.

Background Psychiatric consultation is important in the follow-up of disorders of sex development (DSD) patients. In this study, we aimed to present the 12-year psychiatric follow-up data of the patients who were referred by Ege University Medical Faculty DSD Multidisciplinary Team and followed up in Child and Adolescent Psychiatry. Methods Psychiatric data of 118 patients, who were followed by the DSD multidisciplinary team between 2007 and 2019, were reviewed retrospectively. The psychiatric diagnoses of the patients were evaluated according to semi-structured interview form Schedule for Affective Disorders and Schizophrenia for School-Age Children/Present and Lifetime Turkish Version. Results The mean age of the 118 cases was 13.21 years (±7.18). Endocrine diagnoses of the cases were 46 XX DSD in 35 (29.6%), 46 XY DSD in 81 (68.7%), and chromosome disorders in 2 (1.7%). There was at least psychiatric diagnosis in 36 (30.5%) cases. The most common psychiatric diagnosis was attention deficit and hyperactivity disorder (ADHD) (n = 18, 15.3%). ADHD was most common in congenital adrenal hyperplasia (n = 4, 22.4%) and androgen synthesis defects (ASD) (n = 4, 22.4%); depression was most common in complete gonadal dysgenesis and ASD (n = 3, 23.1%); and mental retardation was most common in ASD (n = 3, 37.5%). Conclusions In order to provide a healthy perspective for cases with DSD, it is important to make a psychiatric evaluation and to share observations and clinical findings in regular team meetings.

Neurofibromatosis Noonan syndrome (NFNS) is a rare RASopathy syndrome, resulting from NF1 gene mutations. NFNS is characterized by phenotypic features of both neurofibromatosis type 1 (NF1) and Noonan syndrome. Plexiform neurofibromas (PNFs) are an unusual finding in NFNS. A seven year-old girl with typical clinical features of NF1 was referred to our clinic due to short stature and abnormal genital appearance. Due to dysmorphic features, a clinical diagnosis of NFNS was considered in the patient and, following molecular analysis, revealed a novel heterozygous c.3052&#95;3056delTTAGT (p.L1018X) variant in the NF1 gene. Although evaluation for genital virilization, including karyotype and hormonal studies were normal, imaging studies revealed a diffuse genital PNF. Although PNFs are seen rarely in NFNS, this should be considered in the differential diagnosis of genital virilization in these patients to prevent unnecessary testing.

Aromatase deficiency rarely causes a 46,XX sexual differentiation disorder. The CYP19A1 gene encodes the aromatase enzyme which catalyses the conversion of androgens to oestrogens. In cases with 46,XX karyotype, mutations in the CYP19A1 gene can lead to disorders of sex development. Clinical findings in aromatase deficiency vary depending on the degree of deficiency. The effect of increased androgens, including acne, cliteromegaly and hirsutism, can be observed in mothers with placental aromatase deficiency. A decrease in maternal virilisation symptoms is observable in the postpartum period. It is rarely reported that there is no virilization in pregnancy. In this study, two 46,XX sibling having the p.R115X (c.343 C>T) novel pathogenic variant in the CYP19A1 gene and raised as different genders, with no maternal virilisation during pregnancy, are presented. In conclusion, 46,XX virilised females should be examined in terms of aromatase deficiency once congenital adrenal hyperplasia has been excluded, even if there is no history of maternal virilisation during pregnancy.

Objective: The aim of this study was to determine the prevalence of impaired hypoglycemia awareness (IHA) in children and adolescents with type 1 diabetes mellitus using a professional continuous glucose monitoring (CGM) system and to show the effect of structured education on glycemic variability (GV) in children and adolescents with IHA., Methods: Forty type 1 diabetic children and adolescents with a diabetes duration of at least five years were eligible for inclusion in this prospective, quantitative study. All subjects were asked about their history of being aware of the symptoms of hypoglycemia using a questionnaire. Professional CGM was conducted in all of the patients for six days. The frequency of IHA detected by comparison of CGM and logbook reports were analyzed. Patients with identified IHA underwent a structured training program. After three months, CGM was re-applied to patients with IHA., Results: The study was completed by 37 diabetic children and adolescents. After the initial CGM, nine patients (24.3%) were found to have had episodes of IHA. Area under the curve (AUC) for hypoglycemia and number of low excursions were; 1.81±0.95 and 8.33±3.60 for the IHA group at the beginning of the study. AUC for hypoglycemia was 0.43±0.47 after three months of structured education the IHA patients (p=0.01). Coefficient of variation which shows primary GV decreased significantly although unstable at the end of education in IHA patients (p=0.03)., Conclusion: CGM is a valuable tool to diagnose IHA. IHA, GV and time in range can be improved by education-based intervention.

Objective: Disorders of sex development (DSD) is a nomenclature intended to defeat the discomfort of families and patients and has found worldwide usage. The aim of this study was to address the perception and usage of terminology among the parents of DSD patients in a tertiary center in western Turkey., Methods: The records of the DSD council (multidisciplinary team where each patient with DSD is discussed) between years 2008-2015 were reviewed retrospectively. Data including details of the management process, patient characteristics and follow-up details were noted. Then inquiries reflecting parental perception about terminology were implemented during clinical visits., Results: In total, 121 patients were evaluated in monthly meetings of the DSD council and 79 inquiries were completed. Fifty-one percent of the families admitted knowing the terms DSD, ambiguous genitalia, “dubious genitals” and intersex. However, only 2% preferred using DSD, 6% intersex and 14% ambiguous genitalia. Fifty-two percent of the parents used a disease name in Latin (mostly hypospadias) addressing the disorder. The offspring of 69% of the parents who were familiar with the name “dubious genitals” were diagnosed in the neonatal period. The preferred terminology used by parents was strongly associated with the terminology used most commonly in the medical speciality their child most often attended., Conclusion: Each country has its own social norms. We suggest therefore that local committees including medical professionals, patients and families should be employed to develop proper terminology.

Objective: To compare continuous subcutaneous insulin infusion (CSII) therapy with multiple daily insulin (MDI) therapy on metabolic control in children and adolescents with type 1 diabetes mellitus (T1DM) over the long term., Methods: Fifty-two T1DM patients treated with CSII and monitored for at least one year prior to and at least five years following CSII were included. Thirty-eight age and sex-matched MDI controls with a 5-year follow up were recruited., Results: Mean age of the subjects, duration of diabetes and CSII therapy were 17.0±4.8 years, 10.7±2.8 years and 7.7±1.5 years respectively. Mean hemoglobin A1c (HbA1c) in the year prior to CSII, during the first year of treatment and after 5 years of CSII were 7.3±1% (56 mmol/mol), 7.0±0.7% (53 mmol/mol) and 7.8±1.3% (62 mmol/mol) respectively. Initial and 5-year mean HbA1C levels of controls were 7.9±1.08% and 8.6±1.8%. Mean HbA1c values were significantly lower in those receiving CSII therapy throughout follow-up. Basal and total insulin doses were significantly lower in the CSII group at all times. HbA1c was compared between subjects by age (0-5, 6-11 and 12-18 years) with no significant difference between them., Conclusion: Although CSII mean HbA1c values exceeded accepted good metabolic control limits after 5 years, CSII produces better HbA1c control at all times and in all age groups compared to MDI.

Maturity onset diabetes is a genetic form of diabetes mellitus characterized by an early age at onset and several etiologic genes for this form of diabetes have been identified in many patients. Maturity onset diabetes type 2 [MODY2 (#125851)] caused by mutations in the glucokinase gene (GCK). Although its prevalence is not clear, it is estimated that 1%-2% of patients with diabetes have the monogenic form. The aim of this study was to evaluate the molecular spectrum of GCK gene mutations in 177 Turkish MODY type 2 patients. Mutations in the GCK gene were identified in 79 out of 177. All mutant alleles were identified, including 45 different GCK mutations, 20 of which were novel., (Copyright © 2017. Published by Elsevier B.V.)

Background: The aim of the study was to assess the response to growth hormone (GH) treatment in very young patients with GH deficiency (GHD) through a national, multi-center study. Possible factors affecting growth response were assessed (especially mini-puberty)., Methods: Medical reports of GHD patients in whom treatment was initiated between 0 and 3 years of age were retrospectively evaluated., Results: The cohort numbered 67. The diagnosis age was 12.4±8.6 months, peak GH stimulation test response (at diagnosis) as 1.0±1.4 ng/mL. The first and second years length gain was 15.0±4.3 and 10.4±3.4 cm. Weight gain had the largest effect on first year growth response; whereas weight gain and GH dose were both important factors affecting second year growth response. In the multiple pituitary hormone deficiency (MPHD) group (n=50), first year GH response was significantly greater than in the isolated GH deficiency (IGHD) group (n=17) (p=0.030). In addition first year growth response of infants starting GH between 0 and 12 months of age (n=24) was significantly greater than those who started treatment between 12 and 36 months of age (n=43) (p<0.001). These differences were not seen in the second year. Δ Length/height standard deviation score (SDS), Δ body weight SDS, length/height SDS, weight SDS in MPHD without hypogonadism for the first year of the GH treatment were found as significantly better than MPHD with hypogonadism., Conclusions: Early onsets of GH treatment, good weight gain in the first year of the treatment and good weight gain-GH dose in the second year of the treatment are the factors that have the greatest effect on length gain in early onset GHD. The presence of the sex steroid hormones during minipubertal period influence growth pattern positively under GH treatment (closer to the normal percentage according to age and gender).

Objective: The aim of this study was to show the reliability and validity of a Turkish version of Diabetes Eating Problem Survey-Revised (DEPS-R) in children and adolescents with type 1 diabetes mellitus., Methods: A total of 200 children and adolescents with type 1 diabetes, ages 9-18 years, completed the DEPS-R Turkish version. In addition to tests of validity, confirmatory factor analysis was conducted to investigate the factor structure of the 16-item Turkish version of DEPS-R., Results: The Turkish version of DEPS-R demonstrated satisfactory Cronbach's ∝ (0.847) and was significantly correlated with age (r=0.194; p<0.01), hemoglobin A1c levels (r=0.303; p<0.01), and body mass index-standard deviation score (r=0.412; p<0.01) indicating criterion validity. Median DEPS-R scores of Turkish version for the total samples, females, and males were 11.0, 11.5, and 10.5, respectively., Conclusion: Disturbed eating behaviors and insulin restriction were associated with poor metabolic control. A short, self-administered diabetes-specific screening tool for disordered eating behavior can be used routinely in the clinical care of adolescents with type 1 diabetes. The Turkish version of DEPS-R is a valid screening tool for disordered eating behaviors in type 1 diabetes and it is potentially important to early detect disordered eating behaviors.

Objective: The management of childhood thyroid nodules is still a big challenge for clinicians. In this study, we aimed to present our surgical and endocrinological experience in more than one hundred pediatric cases., Methods: A retrospective analysis of patients admitted with a thyroid nodule between 2006 and 2014 was performed. Detailed ultrasonography and fine-needle aspiration biopsy (FNAB) were the cornerstones of the diagnostic approach., Results: One hundred-three children (72 female, 31 male) with a mean age of 13.1±3.6 years (3-18 years) were admitted to our center. Management strategy was surgery in 58 patients and follow-up in 45 patients. Mean nodule size was 17±12.7 mm (2-45 mm). The diagnoses were listed as benign solitary nodule (48 patients), thyroid carcinoma (26 patients), multinodular goiter (23 patients), Hashimoto thyroiditis (4 patients), and Graves' disease (2 patients). Surgical procedures were nodulectomy/lobectomy (32 patients), total thyroidectomy (TT) (13 patients), or TT+ neck dissection (13 patients). The rate of malignancy was 25% in the total group and 44% in the surgery group. The malignancy rate was higher in patients younger than 12 years compared to older children (41% vs. 17%, p=0.040). Metastasis was seen in 38% of the malignant nodules. Postoperative complications were transient hypocalcemia (8%), permanent hypocalcemia (1.7%), and unilateral vocal cord paralysis (1.7%). Recurrence or mortality was not encountered in the 5.4±1.2-year follow-up period., Conclusion: Thyroid nodule in a child requires an aggressive diagnostic approach due to increased risk of malignancy and metastasis. Intraoperative frozen section examination must be done as a useful adjunct to determine the surgical strategy. Incidence of complications is small in thyroid surgery when performed by experienced surgeons.

Persistent Müllerian duct syndrome is the result of either anti-Müllerian hormone (AMH) deficiency or AMH receptor resistance. A long tubular structure was palpated during the physical examination of a 13-month-old male patient who had presented with bilateral undescended testes. At physical examination, the testes were not palpable. The patient's karyotype was XY, SRY (+), and his AMH level was 22 ng/mol. Structures suggestive of ovaries, a uterus, and fallopian tubes were observed during the laparoscopic examination of the ectopic testis. AMHR2 gene sequence analysis performed with a preliminary diagnosis of AMH receptor resistance revealed a previously unreported homozygous c.24G>A (p.W8X) mutation. The patient was assessed as a case of AMH receptor resistance. Orchiopexy was performed.

Background: Vesicoureteral reflux and urinary tract infection predispose children to retardation of growth, hypertension, renal scarring and renal failure. The aim of this study was to evaluate growth pattern in children with vesicoureteral reflux before and after medical/surgical treatment., Methods: This study was a retrospective cross-sectional study. The study population included 97 children aged 0.5 to 17 years (8.8±5.5). Body weight, height and bone age of the children were measured. Weight Z score and height Z score were calculated during first visits and after medical and/or surgical treatment. Distribution, mean and standard deviation score were evaluated for the descriptive data. T-test and Mann-Whitney U test and Wilcoxon test were used for statistical analysis., Results: Sixty-five percent of 97 children enrolled in this study were girls. About 48.5% of the children had unilateral and mild reflux, while 16.5% had bilateral and severe reflux. The bone age was 8.6 years. Differentiation with chronological age and bone age were not significant (P=0.294). At admission, 54.6% and 50.5% of children had negative Weight Z score and height Z score, respectively. After medical and surgical treatment, Weight Z score and height Z score were increased, however, only the increase in Weight Z score was significant (P=0.039, P=0.031, respectively). A significant reduction in bone age was found in children with renal scars compared to those without renal scars (P=0.048)., Conclusions: High-grade vesicoureteral reflux had a negative impact on indices of growth in children. Medical and/or surgical treatment had positive effect on weight gain.

Background/aim: The aim of this study was to use targeted next-generation sequencing (TNGS) including all known genes associated with 46,XY disorders of sex development (DSD) for a fast molecular genetic diagnosis., Methods: Twenty pediatric patients were recruited, and 56 genes related to 46,XY DSD were sequenced using TNGS. The time elapsed between initial appointment and final diagnosis as well as the mean expenditure was determined., Results: A total of 9 (45%) mutations in 4 different genes were identified. Mutations in the HSD17B3 gene were observed in 6 (30%) patients. A heterozygous mutation in WT1 gene and a hemizygous mutation in SRY gene were detected in patients with gonadal dysgenesis. One patient had a homozygous mutation in LHCGR gene. Prior to the molecular diagnosis, the mean number of clinical visits, time elapsed until diagnosis, and expenditure were 27.4 ± 14.6 visits, 5.9 ± 4.1 years per patient, and USD 2,142 ± 1,038, respectively. With TNGS, time elapsed until diagnosis was significantly reduced (3 days), and expenditure per patient was only one third of the conventional approach (USD 761)., Conclusions: TNGS is an efficient, rapid, and cost-effective technique for mutation detection in 46,XY DSD., (© 2016 S. Karger AG, Basel.)

Aims: To evaluate the management strategies, glycemic control and complications of pediatric type 1 diabetes mellitus (T1DM) patients in Turkey., Methods: Study included 498 patients with T1DM between the ages 1-18. Data provided from patients' hospital files were recorded on standard case report forms by applicant clinicians within the 3months of data collection period between October 2012 and July 2013., Results: Mean age of patients was 11.3±3.8years. Mean duration of DM was determined as 3.7±3.1years. Majority of patients (85.5%) used basal/bolus injection (BBI), and 6.5% used continuous subcutaneous insulin infusion pump. Assessment of glycemic control based on HbA1c levels showed that 29.1% of patients had an HbA1c value <7.5% (58mmol/mol), 16.1% had a value between 7.5% (58mmol/mol) and 8% (64mmol/mol), 19.1% had a value between 8.1% (64mmol/mol) and 9%(75mmol/mol) and 35.7% a value >9%(75mmol/mol). Hypoglycemia was reported in 145 (29.1%) patients and the number of severe hypoglycemic attacks in the last 3months was 1.0±2.4. Taking into consideration the carbohydrate count and insulin correction dose and parents with high socioeconomic status was related to have better glycemic control. The most common comorbidities were Hashimoto's thyroiditis/hypothyroidism (6.2%) followed by celiac disease (3.8%), epilepsy(1.2%), and asthma(1.0%)., Conclusions: BBI insulin therapy is widely used among pediatric T1DM patients in Turkey. However, despite improvements in treatment facilities and diabetic care, glycemic control is not at a satisfactory level. Therefore, new and comprehensive initiatives require for pediatric T1DM patients with poor glycemic control. Promoting use of carbohydrate count and insulin correction doses may improve the glycemic control of pediatric T1DM in Turkey., (Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.)

Objective: What initiates the pubertal process in humans and other mammals is still unknown. We hypothesized that gene(s) taking roles in triggering human puberty may be identified by studying a cohort of idiopathic hypogonadotropic hypogonadism (IHH)., Methods: A cohort of IHH cases was studied based on autozygosity mapping coupled with whole exome sequencing., Results: Our studies revealed three independent families in which IHH/delayed puberty is associated with inactivating SRA1 variants. SRA1 was the first gene to be identified to function through its protein as well as noncoding functional ribonucleic acid products. These products act as co-regulators of nuclear receptors including sex steroid receptors as well as SF-1 and LRH-1, the master regulators of steroidogenesis. Functional studies with a mutant SRA1 construct showed a reduced co-activation of ligand-dependent activity of the estrogen receptor alpha, as assessed by luciferase reporter assay in HeLa cells., Conclusion: Our findings strongly suggest that SRA1 gene function is required for initiation of puberty in humans. Furthermore, SRA1 with its alternative products and functionality may provide a potential explanation for the versatility and complexity of the pubertal process.

To evaluate the anthropometric features of girls with Turner syndrome (TS) at birth and presentation and the effect of karyotype on these parameters. Data were collected from 842 patients with TS from 35 different centers, who were followed-up between 1984 and 2014 and whose diagnosis age ranged from birth to 18 years. Of the 842 patients, 122 girls who received growth hormone, estrogen or oxandrolone were excluded, and 720 girls were included in the study. In this cohort, the frequency of small for gestational age (SGA) birth was 33%. The frequency of SGA birth was 4.2% (2/48) in preterm and 36% (174/483) in term neonates (P < 0.001). The mean birth length was 1.3 cm shorter and mean birth weight was 0.36 kg lower than that of the normal population. The mean age at diagnosis was 10.1 ± 4.4 years. Mean height, weight and body mass index standard deviation scores at presentation were -3.1 ± 1.7, -1.4 ± 1.5, and 0.4 ± 1.7, respectively. Patients with isochromosome Xq were significantly heavier than those with other karyotype groups (P = 0.007). Age at presentation was negatively correlated and mid-parental height was positively correlated with height at presentation. Mid-parental height and age at presentation were the only parameters that were associated with height of children with TS. The frequency of SGA birth was found higher in preterm than term neonates but the mechanism could not be clarified. We found no effect of karyotype on height of girls with TS, whereas weight was greater in 46,X,i(Xq) and 45,X/46,X,i(Xq) karyotype groups., (© 2016 Wiley Periodicals, Inc.)

Ataxia-telangiectasia (A-T) is a rare autosomal recessive, multisystem, neurodegenerative disorder, characterized by oculocutaneous telangiectasias, variable immunodeficiency and progressive neurological impairment. Definitive diagnosis is made by revealing a disease causing mutation on ATM gene. Missense mutations and polymorphisms of ATM gene can play a role in the development of thyroid papillary carcinoma. A 13-year-old Turkish girl was diagnosed with ataxia telengiectasia at the age of 8 years. When she was 12 years old, multi-nodular goiter was detected by physical examination and ultrasonography. She underwent thyroidectomy and histopathologic investigation revealed a papillary carcinoma with follicular variant. The patient received post-operative radioiodine therapy as well as L-thyroxine treatment because she had residual lesions. Up until now, she is the first Turkish child wit A-T and thyroid carcinoma described in the literature.

The aim of this anti-Mullerian hormone (AMH) levels in prepubertal obese girls are a predictive marker for polycystic ovary syndrome (PCOS) and to investigate the relationship between insulin resistance and AMH. Sixty girls with premature pubarche or obesity and 20 healthy controls between the ages of 6-9 were enrolled. Of the patients, 22 (36.7%) were in the obese group (Group 1), 28 (46.7%) in the early pubarche group (Group 2) and 10 (16.6%) in the early pubarche + obese group (Group 3). Comparison of the subjects' fasting insulin and homeostatic model assessment insulin resistance (HOMA-IR) demonstrated significantly higher values for group 1 compared to group 2 (p=0.001 and 0.001) and, likewise, significantly higher values for group 3 compared to group 2. There was no significant differences between all groups for AMH levels. AMH levels were not significantly different in the obese girls compared to the other groups. There was also no relationship between AMH and insulin resistance in any of the groups. Further studies, however, are needed due the limited number of subjects in this study and in the absence of adequate relevant data.

Objective: Children with Turner syndrome (TS) have a specific growth pattern that is quite different from that of healthy children. Many countries have population-specific growth charts for TS. Considering national and ethnic differences, we undertook this multicenter collaborative study to construct growth charts and reference values for height, weight and body mass index (BMI) from 3 years of age to adulthood for spontaneous growth of Turkish girls with TS., Methods: Cross-sectional height and weight data of 842 patients with TS, younger than 18 years of age and before starting any therapy, were evaluated., Results: The data were processed to calculate the 3rd, 10th, 25th, 50th, 75th, 90th and 97th percentile values for defined ages and to construct growth curves for height-for-age, weight-for-age and BMI-for-age of girls with TS. The growth pattern of TS girls in this series resembled the growth pattern of TS girls in other reports, but there were differences in height between our series and the others., Conclusion: This study provides disease-specific growth charts for Turkish girls with TS. These disease-specific national growth charts will serve to improve the evaluation of growth and its management with growth-promoting therapeutic agents in TS patients.

To investigate the specific mutations in PROP1, POU1F1, LHX3, and HESX1 genes in patients with combined pituitary hormone deficiency (CPHD) in Turkey. Seventy-six patients with CPHD were included in this study. Based on clinical, hormonal, and neuro-radiological data, relevant transcription factor genes were evaluated by Sanger sequencing and multiplex ligation-dependent probe amplification. Total frequency of mutations was 30.9 % in patients with CPHD. Frequency was significantly higher in familial patients (p = 0.001). Three different types of mutations in PROP1 gene (complete gene deletion, c.301-302delAG, a novel mutation; IVS1+2T>G) were found in 12 unrelated patients (21.8 %). Mutations in PROP1 gene were markedly higher in familial than in sporadic cases (58.8 vs. 5.3 %, p < 0.001). Homozygous complete gene deletion was the most common mutation in PROP1 gene (8/12) and was identified in six familial patients. Four different homozygous mutations [p.Q4X, novel mutations; exons 1-2 deletion, p.V153F, p.I244S] were detected in POU1F1 gene. Central precocious puberty was firstly observed in a sporadic-male patient with homozygous POU1F1 (p.I244S) mutation. A homozygous mutation in HESX1 gene (p.R160H) was detected in one patient. This study is the first to investigate specific mutations in CPHD patients in Turkey. Complete deletion in PROP1 gene was the most common mutation encountered in patients with CPHD. We believe that the results of this study will contribute to the establishment of genetic screening strategies in Turkey, as well as to the studies on phenotype-genotype correlations and early diagnosis of CPHD patients.

Background/aims: Loss of function mutations of proopiomelanocortin (POMC) gene results in adrenal insufficiency, early-onset hyperphagic obesity, and red hair. However, neuromotor retardation with POMC deficiency has not been reported before., Case Report: We report a female patient whose initial diagnosis was neurometabolic disease because of motor mental retardation, ataxia, and bilateral hyperintense lesions in the basal ganglia in cranial magnetic resonance imaging, increased lactate-lipid peak in proton magnetic resonance spectroscopy. She was consulted due to rapid weight gain, obesity, and episodes of hypoglycemia and homozygous mutation (c.64delA) in POMC gene was found., Conclusion: Severe motor mental retardation and cranial magnetic resonance imagingpathology in patients with POMC deficiency have not been reported previously in the literature. Bilateral hyperintense lesions in the basal ganglia and the increased lactate-lipid peak was thought to be the result of recurrent hypoglycemia.

Objective: Approaches to diagnosis and treatment of growth hormone deficiency (GHD) in children vary among countries and even among centers in the same country. This survey, aiming to facilitate the process of preparing the new consensus on GHD by the Turkish Pediatric Endocrinology and Diabetes Society, was designed to evaluate the current practices in diagnosis and treatment of GHD in different centers in Turkey., Methods: A questionnaire covering relevant items for diagnosis and treatment of GHD was sent out to all pediatric endocrinology centers., Results: Twenty-four centers returned the questionnaire. The most frequently used GH stimulation test was L-dopa, followed by clonidine. Eighteen centers used a GH cut-off value of 10 ng/mL for the diagnosis of GHD; this value was 7 ng/mL in 4 centers and 5 ng/mL in 2 centers. The most frequently used assay was immunochemiluminescence for determination of GH, insulin-like growth factor-1 and insulin-like growth factor binding protein-3 concentrations. Sex steroid priming in both sexes was used by 19 centers. The most frequently used starting dose of recombinant human GH (rhGH) in prepubertal children was 0.025-0.030 mg/kg/day and 0.030-0.035 mg/kg/day in pubertal children. Growth velocity was used in the evaluation for growth response to rhGH therapy in all centers. Anthropometric measurements of patients every 3-6 months, fasting blood glucose, bone age and thyroid panel evaluation were used by all centers at follow-up. Main indications for cessation of therapy were decreased height velocity and advanced bone age. Fourteen centers used combined treatment (rhGH and gonadotropin-releasing analogues) to increase final height., Conclusion: Although conformity was found among centers in Turkey in current practice, it is very important to update guideline statements and to modify, if needed, the approach to GHD over time in accordance with new evidence-based clinical studies.

Objective: Turner syndrome (TS) is a chromosomal disorder caused by complete or partial X chromosome monosomy that manifests various clinical features depending on the karyotype and on the genetic background of affected girls. This study aimed to systematically investigate the key clinical features of TS in relationship to karyotype in a large pediatric Turkish patient population., Methods: Our retrospective study included 842 karyotype-proven TS patients aged 0-18 years who were evaluated in 35 different centers in Turkey in the years 2013-2014., Results: The most common karyotype was 45,X (50.7%), followed by 45,X/46,XX (10.8%), 46,X,i(Xq) (10.1%) and 45,X/46,X,i(Xq) (9.5%). Mean age at diagnosis was 10.2±4.4 years. The most common presenting complaints were short stature and delayed puberty. Among patients diagnosed before age one year, the ratio of karyotype 45,X was significantly higher than that of other karyotype groups. Cardiac defects (bicuspid aortic valve, coarctation of the aorta and aortic stenosis) were the most common congenital anomalies, occurring in 25% of the TS cases. This was followed by urinary system anomalies (horseshoe kidney, double collector duct system and renal rotation) detected in 16.3%. Hashimoto's thyroiditis was found in 11.1% of patients, gastrointestinal abnormalities in 8.9%, ear nose and throat problems in 22.6%, dermatologic problems in 21.8% and osteoporosis in 15.3%. Learning difficulties and/or psychosocial problems were encountered in 39.1%. Insulin resistance and impaired fasting glucose were detected in 3.4% and 2.2%, respectively. Dyslipidemia prevalence was 11.4%., Conclusion: This comprehensive study systematically evaluated the largest group of karyotype-proven TS girls to date. The karyotype distribution, congenital anomaly and comorbidity profile closely parallel that from other countries and support the need for close medical surveillance of these complex patients throughout their lifespan.

Objective: To assess the efficacy of intraoperative parathyroid hormone (PTH) monitoring in evaluating the outcome of parathyroidectomy in pediatric patients., Methods: Intraoperative PTH monitoring during parathyroidectomy was performed in five children (3M, 2F); three had parathyroid adenomas (single gland disease) and two had primary hyperplasia. One patient had undergone two previous surgical interventions to remove the parathyroid glands, but the PTH levels had remained high with persistence of symptoms. Immunoradiometric analysis was used for PTH measurements. Preoperative PTH values were obtained to monitor the baseline levels. Serum samples were collected 20 minutes after removal of the adenoma/parathyroid gland(s) and PTH levels were compared with preoperative values. Specimens were also confirmed by frozen sectional examination., Results: Mean age of the patients was 11 years (range: 3 months-16 years). Mean preoperative PTH values were 633.3±579 pg/mL (range: 143-1300 pg/mL). Intraoperative values decreased to 18.7±5.5 pg/mL (range: 8-27 pg/mL) following removal of the gland(s). Normal calcium levels were achieved with adequate management following surgery. One patient (with multiple surgeries and found to have an ectopic parathyroid gland) had hungry bone syndrome after the operation and was treated successfully. There were no major complications. All patients maintained normal calcium/phosphorus levels in the follow-up period, ranging from 2 to 5 years., Conclusion: An ectopic parathyroid gland or another undetected adenoma can be overlooked during surgery. Owing to the short life of the hormone, intraoperative PTH monitoring to determine PTH clearance proved to be a feasible marker for adequacy and safety of surgery and "cure".

Objective: Epidemiologic and clinical features of type 1 diabetes mellitus (T1DM) may show substantial differences among countries. The primary goal in the management of T1DM is to prevent micro- and macrovascular complications by achieving good glycemic control. The present study aimed to assess metabolic control, presence of concomitant autoimmune diseases, and of acute and long-term complications in patients diagnosed with T1DM during childhood and adolescence. The study also aimed to be a first step in the development of a national registry system for T1DM, in Turkey., Methods: Based on hospital records, this cross-sectional, multicenter study included 1 032 patients with T1DM from 12 different centers in Turkey, in whom the diagnosis was established during childhood. Epidemiological and clinical characteristics of the patients were recorded. Metabolic control, diabetes care, complications, and concomitant autoimmune diseases were evaluated., Results: Mean age, diabetes duration, and hemoglobin A1c level were 12.5 ± 4.1 years, 4.7 ± 3.2 years, and 8.5 ± 1.6%, respectively. Acute complications noted in the past year included ketoacidosis in 5.2% of the patients and severe hypoglycemia in 4.9%. Chronic lymphocytic thyroiditis was noted in 12%, Graves' disease in 0.1%, and celiac disease in 4.3% of the patients. Chronic complications including neuropathy, retinopathy, and persistent microalbuminuria were present in 2.6%, 1.4%, and 5.4% of the patients, respectively. Diabetic nephropathy was not present in any of the patients. Mean diabetes duration and age of patients with neuropathy, retinopathy and microalbuminuria were significantly different from the patients without these long-term complications (p<0.01). A significant difference was found between pubertal and prepubertal children in terms of persistent microalbuminuria and neuropathy (p=0.02 and p<0.001, respectively). Of the patients, 4.4% (n:38) were obese and 5% had short stature; 17.4% of the patients had dyslipidemia, and 14% of the dyslipidemic patients were obese., Conclusions: Although the majority of the patients in the present study were using insulin analogues, poor glycemic control was common, and chronic complications were encountered.

Aromatase deficiency (AD) is a rare autosomal recessive inheritance syndrome. Its worldwide incidence is unknown, and there are few case reports in the literature. Aromatase dysfunction develops due to CYP19A1 gene mutation and a decrease in estrogen synthesis. Estrogen deficiency can induce delayed epiphyseal closure, eunuchoid body habitus, osteopenia, and osteoporosis in both genders. Our patient was a 27-year-old male who presented with bone pain, recurrent bone fractures associated with minimal trauma starting in puberty, and a progressive increase in height. Laboratory tests revealed that the blood levels of follicle-stimulating hormone and luteinizing hormone were above normal, testosterone level was normal, and estrogen was undetectable. Plain bone radiography of the left wrist and hand demonstrated that the epiphyses were still unfused. Lumbar osteoporosis was detected in bone densitometry. In the genetic analysis, homozygous R375H guanine-adenine (G-A) mutation was detected in the CYP19A1 gene, and a diagnosis of AD was reached. Treatment with 25 μg transdermal estradiol was started. All family members were examined. Homozygous R375H G-A mutation was detected in the patient's younger brother. Heterozygous R375H G-A mutation was found in his mother, father, and older brother. In conclusion, this AD patient requires lifetime estrogen replacement in order to provide sufficient bone mineralization, to reduce the risk of bone fractures, and to lead a healthy life. The best method to prevent the possible complications is to diagnose the AD syndrome at early ages and to provide adequate estrogen replacement starting at puberty.

Objective: Disorders of sex development (DSD) are a group of congenital medical conditions that affect life as a whole. In this study, we aimed to reflect the experience of a multidisciplinary team in the clinical/psychiatric follow-up of a group of children and adolescents with DSD., Methods: The study group consisted of 51 patients diagnosed with DSD. The Kiddie-Schedule for Affective Disorders and Schizophrenia, Wechsler Intelligence Scale for Children-Revised, Draw a Person Test and Children's Apperception Test, and the Clinical Global Impression Scale (CGIS) were used for psychiatric evaluations., Results: The mean age of the patients was 7.8 years (median: 7.8; min: 1.0; max: 18.0). Genetic evaluation showed 46,XX configuration in 15 patients (29.4%) and 46,XY in 35 (68.6%). One patient (2.0%) was diagnosed to have a sex chromosome disorder. Forty patients (78.4%) had no problems with their given gender identity and gender role. Thirty-four (66.7%) patients had normal intellectual capacity. Twenty-eight (54.9%) patients did not have any psychiatric problem. Depression, anxiety disorders, attention deficit/hyperactivity disorder, and adjustment disorders were the common diagnoses. The mean score of symptom severity on CGIS-severity-baseline was 6.15±0.68 and after one year, it was 1.46±0.51 (Z=-3.236 p=0.001). The mean score of CGI-Improvement was 1.23±0.44., Conclusion: It is important to identify and treat the psychiatric disorders encountered in patients with DSD. A psychiatrist needs to be included in the professional team following these patients. Examination and observation results need to be shared by holding periodic team meetings to establish a wholesome point of view for every unique child.

Background/aim: The exon 3-deleted/full-length (d3/fl) growth hormone (GH) receptor (GHR) polymorphism has been associated with responsiveness to GH therapy in some diagnostic groups. However, there are still controversies on this issue. To evaluate the effect of the GHR exon 3 polymorphism on growth after 1 and 2 years of GH therapy in Turkish patients with GH deficiency (GHD) and Turner's syndrome (TS) and the distribution of GHR exon 3 isoforms., Materials and Methods: 218 patients with GHD (125 males/93 females) and 43 patients with TS were included in the study. The control group included 477 healthy adults aged from 18 to 57 years (54 females/423 males). Anthropometric parameters and insulin-like growth factor (IGF)-1 and IGF binding protein (IGFBP)-3 were evaluated annually. GHR isoforms were studied using simple multiplex PCR. Height and body mass index were expressed as standard deviation score (SDS)., Results: There were no differences among TS, GHD and healthy adults regarding the distribution of GHR exon 3 isoforms (fl/fl, fl/d3 and d3/d3). There was a significant increase in height SDS in both diagnostic groups on GH therapy; however, there were neither differences in height SDS and Δheight velocity between fl/fl, fl/d3 and d3/d3 groups nor a correlation between the distribution of GHR exon 3 isoforms and change in IGF-1 SDS and IGFBP-3 SDS levels on GH therapy in either of the diagnostic groups. There was also no gender difference in GHR isoforms in healthy adults., Conclusion: The results suggest that responsiveness to GH therapy does not depend on the exon 3 GHR genotypes in GHD and TS patients., (Copyright © 2012 S. Karger AG, Basel.)