Comprehensive Insights into Pediatric Craniopharyngioma: Endocrine and Metabolic Profiles, Treatment Challenges, and Long-term Outcomes with a Multicenter Approach.

Introduction: Craniopharyngiomas (CPG) have complex challenges in treatment due to their proximity to vital structures, surgical and radiotherapeutic complexities, and the tendency for recurrence. This study aims to identify the prevalence of endocrine and metabolic comorbidities observed during initial diagnosis and long-term follow-up in a nationwide cohort of pediatric CPG patients. The study also highlights the associated difficulties in their management. Methods: Sixteen centers entered 152 patients into the ÇEDD NET data system. We evaluated the clinical and laboratory characteristics at presentation, administered treatments, accompanying endocrine, metabolic, and other system involvements, and the patient's follow-up features. Results: Of the evaluated patients, 64 were female, and 88 were male. At presentation, the mean age was 9.1 ± 3.67 (min:1.46-max:16.92) years. The most common complaints at presentation were headache (68.4%), vision problems (42%), short stature (15%), nausea and vomiting (7%). The surgical procedure applied to the patients was gross total resection (GTR) in 97 cases (63.8%) and subtotal resection in 55 cases (36.2%). Radiotherapy was initiated in 11.8% of the patients. In the pathological examination, 92% of the cases were adamantinamatous type, 8% were papillary type. Postoperatively, hormone deficiencies consisted of thyroid-stimulating hormone (92.1%), adrenocorticotropic hormone (81%), antidiuretic hormone (79%), growth hormone (65.1%), and gonadotropin (43.4%) deficiencies. Recombinant growth hormone treatment (rhGH) was initiated on 27 patients. The study showed hesitancy among physicians regarding rhGH. The median survival without relapse was 2.2 years. Median time of relapse was 1.82 years (range: 0.13-10.35 years). Relapse was related to longer follow-ups and reduced GTR rates. The median follow-up time was 3.13 years. Among the last follow-up visits, the prevalence of obesity was 38%, but of these, 46.5% were already obese at diagnosis. However, 20% who were not obese at baseline became obese on follow-up. Permanent visual impairment was observed in 26 patients, neurological deficits in 13 patients, and diabetes mellitus in 5 patients. Conclusion: Recurrence was predominantly due to incomplete resection and the low rate of postoperative radiotherapy. It also emphasized challenges in multidisciplinary regular follow ups and suggested early interventions such as dietary restrictions and increased exercise to prevent obesity.

A Rare Case of Monogenic Obesity due to a Novel Variant in the ADCY3 Gene: Challenges in Follow-up and Treatment.

Adenylate cyclase 3 (ADCY3) gene alterations have been found to be associated with obesity. However, few patients with homozygous mutations have been reported so far, and the follow-up procedure and treatment options have not been clarified. A 10-month-old female presented with increased appetite and weight gain. She was born from a consanguineous marriage. Weight, height, head circumference measurements and standard deviation scores (SDS) were 19 kg (+6.98 SDS), 82 cm (+3.53 SDS), and 49 cm (+3.07 SDS), respectively. Laboratory tests revealed a fasting glucose level of 103 mg/dL (5.7 mmol/L), insulin level of 25.39 µIU/mL, and Homeostatic Model Assessment for Insulin Resistance (HOMA-IR) value of 6.43. Whole-exome sequencing revealed a novel, homozygous c.1102G>A(p.Asp368Asn) variant in ADCY3. Her parents and healthy sister were heterozygous for the variant. At the age of 2.5 years, neurodevelopmental delay was observed. At the age of 3.5 years, the patient's weight, height, and body mass index values were 49.5 kg (+8.16 SDS), 111 cm (+2.59 SDS), and 40.18 kg/m2 (+6.48 SDS), respectively. Signs of Blount's disease and acanthosis nigricans were distinctive, and she had hyperphagia. She was undergoing speech therapy. Homozygous ADCY3 variants may present with early onset, severe obesity, insulin resistance, and neurodevelopmental delay in children. Severe complications may occur even at young ages. More data regarding the follow-up process and treatment of these patients are needed.

The association between vitamin B12, folate, homocysteine levels, and carotid intima-media thickness in children with obesity: a cross-sectional study.

OBJECTIVES: We aimed to evaluate the association between vitamin B12, folate, homocysteine levels, and carotid intima-media thickness (CIMT) among children with obesity in whom vitamin deficiencies are more frequent. METHODS: Herein, 100 children with obesity (58 girls) were included (age, 5-18 years). Height, weight, body mass index (BMI), waist circumference (WC), puberty stage, blood pressure, and biochemical values were collected from medical records; standard deviations (SDS) and percentiles were calculated. Obesity was defined as BMI SDS of >+2SDS. Vitamin B12 and folate levels of <300 pg/mL and <4.8 ng/mL, respectively, were considered deficient. A radiologist quantified measurements from the carotid artery. RESULTS: Mean patient age was 12.52 ± 3.63 years. The mean weight SDS, BMI SDS, and WC/height were +3.37 ± 0.93, +2.93 ± 0.55, and 0.65 ± 0.05, respectively. In pubertal cases, insulin (p<0.001), the homeostatic model assessment for insulin resistance (HOMA-IR) (p=0.001) and homocysteine (p=0.002) levels were higher; vitamin B12 (p<0.001) and folate (p<0.001) levels were lower than those in prepubertal ones. WC and HOMA-IR correlated with CIMT; however, homocysteine levels were not correlated with CIMT. CONCLUSIONS: In our study, pubertal cases had lower vitamin B12 and folate levels as well as higher homocysteine levels. Although no correlation was identified between homocysteine levels and CIMT, this condition may be related to our study group comprising children, who had a shorter duration of obesity than those in adults. As CIMT was higher in children/adolescents with increased WC, it is proposed that they need central obesity more frequently and carefully follow-up.

Factors Affecting Metabolic Bone Disease of Prematurity: Is Hypothyroxinemia Included?

Objectives: The association between transient hypothyroxinemia of prematurity (THOP) and metabolic bone disease of prematurity (MBD) is not clearly known. We aimed to evaluate the effects of THOP and other risk factors on MBD in very low birth weight infants. Methods: This study included infants born at <30 weeks gestational age and <1500 g birth weight who were hospitalized between July 2016 and December 2019. The following information was obtained from medical records: Demographic characteristics; clinical follow-up data; morbidities; initial thyroid function tests; and calcium (Ca), phosphorus (P), and alkaline phosphatase (ALP) levels at postnatal 4-6 weeks. Newborns with an ALP level >500 IU/L were diagnosed with MBD. Patients without MBD were defined as Group 1 and patients with MBD were defined as Group 2. Results: Our study enrolled 145 infants who met the inclusion criteria. The incidences of MBD and THOP were 16.5% and 56.5%, respectively. Gestational age and birth weight were significantly lower in Group 2 than in Group 1. It was observed that these infants received total parenteral nutrition for a longer period of time and had a longer transition period to full enteral feeding. In addition, duration of non-invasive mechanical ventilation, duration of oxygen treatment, frequencies of moderate-severe bronchopulmonary dysplasia, and postnatal steroid use were found to be significantly higher in babies in Group 2 compared to babies in Group 1. There was no significant difference between the groups in terms of THOP. However, multivariate logistic regression analysis revealed no risk factors for the development of MBD. The presence of MBD and Ca, P, and ALP levels did not differ significantly between patients with and without THOP. Conclusion: Our study reveals that MBD is a multifactorial disease and THOP is not a risk factor for the development of MBD.

Evaluation of the impact of childhood obesity on retrobulbar hemodynamics and retinal microvasculature.

OBJECTIVE: To evaluate changes in retrobulbar ocular blood flow parameters by using Colour Doppler Imaging (CDI) and changes in foveal microvasculature by using Optical Coherence Tomography Angiography (OCTA) in pediatric obese patients and to compare them with a group of healthy children. METHODS: Children diagnosed with obesity without hypertension and diabetes (39 subjects, obese group) and age-matched healthy controls (26 subjects, control group) underwent CDI and OCTA imaging. Peak systolic velocity, end-diastolic velocity and resistivity index from ophthalmic, central retinal and posterior ciliary arteries on CDI; superficial and deep capillary plexus vascular density and foveal avascular zone area on OCTA imaging were obtained in each group. Central foveal and subfoveal choroidal thicknesses were also measured. CDI and OCTA parameters were compared between two groups. RESULTS: Peak systolic and end-diastolic velocities were found to be significantly lower in obese children than in controls in all three examined arteries (p < 0.05). Resistivity index values were similar between the groups. OCTA imaging did not reveal significant changes in superficial and deep capillary plexus vascular densities and foveal avascular zone area across analysed retinal regions between the groups. Subfoveal choroid was thicker in obese group than in control group (325.89 ± 52.77 µm vs. 304.52 ± 21.76 µm, p = 0.04). CONCLUSION: An apparent decrease was present in retrobulbar hemodynamics in obese children. This arises the possibility of early ocular macrovascular compromise rather than retinal microvascular impairment in childhood obesity.

Associations of Respiratory Distress Syndrome Severity and Other Factors With Transient Hypothyroxinemia of Prematurity.

Aim This study examined the associations of respiratory distress syndrome (RDS) severity and other factors on thyroid hormone levels in very low birth weight (VLBW) infants. Methods The demographic characteristics, clinical course, morbidity, and initial thyroid function test results of VLBW infants diagnosed with RDS between July 2016 and September 2018 were obtained retrospectively. RDS severity was determined according to the requirement for multiple surfactants. Patients were divided into groups without and with hypothyroxinemia, and variables of interest were compared between the two groups. Results Our study involved 98 infants meeting the inclusion criteria; the incidence of hypothyroxinemia was 56.1%. Free T4 (fT4) levels were found to be negatively correlated with gestational week (p < 0.001) and birth weight (p < 0.001). The fT4 levels were significantly lower in infants requiring multiple surfactant doses. In infants with hypothyroxinemia, the duration of invasive mechanical ventilation and oxygen treatment was longer and hemodynamically significant patent ductus arteriosus, grade ≥ 3 intraventricular hemorrhage, and moderate to severe bronchopulmonary dysplasia were more common. Multiple pregnancy (odds ratio (OR) = 5.616, 95%; confidence interval (CI): 1.765-17.874) and the duration of invasive mechanical ventilation (OR = 1.05, 95%; CI: 1.005-1.096) were significant risk factors for the development of hypothyroxinemia in logistic regression analysis. Conclusions Transient hypothyroxinemia of prematurity is associated with RDS severity and early morbidities of prematurity. In the presence of multiple pregnancy, patients should be followed up more closely due to the possibility of hypothyroxinemia.

Evaluation of clinical, endocrine and metabolic findings in obese children with and without hepatosteatosis.

OBJECTIVES: Non-alcoholic fatty liver disease (NAFLD) is a common obesity-related comorbidity in childhood. In this study, we aimed to evaluate predictors of NAFLD by comparing clinical, endocrine and metabolic findings in obese children with and without hepatosteatosis. METHODS: Two hundred and eight obese children aged 6-18 years were included. The patients were divided into group 1 (patients with NAFLD, n=94) and group 2 (patients without NAFLD, n=114). Anthropometric measurements, pubertal stage, lipid profiles, fasting glucose and insulin, homeostatic model of assessment for insulin resistance (HOMA-IR), uric acid, total bilirubin, alanine aminotransferase (ALT), blood urea nitrogen, thyroid-stimulating hormone and free thyroxine parameters were compared retrospectively. RESULTS: The mean body weight, body mass index (BMI), height, tri-ponderal mass index (TMI), insulin, HOMA-IR, triglyceride, ALT and uric acid values were significantly higher, while high-density lipoprotein-cholesterol (HDL-C) values were significantly lower in group 1. The 70.7% of obese children with hepatosteatosis and 83.9% of those without hepatosteatosis were correctly estimated by parameters including age, gender, ALT, HDL-C, fasting insulin and uric acid values. CONCLUSIONS: Since obesity-associated hepatosteatosis induces various long-term metabolic impacts in children, early detection is of critical importance. Age, gender, TMI, BMI, ALT, HDL-C, fasting insulin and uric acid values may help to predict the risk of hepatosteatosis. Besides, we assessed whether TMI compared to BMI does not have a better utility in estimating obesity-induced hepatosteatosis in children. This is the first study to show the association between TMI and hepatosteatosis in children.

Clinical Characteristics and Growth Hormone Treatment in Patients with Prader-Willi Syndrome

Objective: To investigate clinical characteristics and response to growth hormone (GH) treatment in patients with Prader-Willi syndrome (PWS) in Turkey. Methods: The data of 52 PWS patients from ten centers was retrospectively analyzed. A nation-wide, web-based data system was used for data collection. Demographic, clinical, genetic, and laboratory data and follow-up information of the patients were evaluated. Results: The median age of patients at presentation was 1.5 years, and 50% were females. Genetic analysis showed microdeletion in 69.2%, uniparental disomy in 11.5%, imprinting defect in 1.9% and methylation abnormality in 17.3%. Hypotonia (55.7%), feeding difficulties (36.5%) and obesity (30.7%) were the most common complaints. Cryptorchidism and micropenis were present in 69.2% and 15.3% of males, respectively. At presentation, 25% had short stature, 44.2% were obese, 9.6% were overweight and 17.3% were underweight. Median age of obese patients was significantly higher than underweight patients. Central hypothyroidism and adrenal insufficiency were present in 30.7% and 4.7%, respectively. Hypogonadism was present in 75% at normal age of puberty. GH treatment was started in 40% at a mean age of 4.7±2.7 years. After two years of GH treatment, a significant increase in height SDS was observed. However, body mass index (BMI) standard deviation (SDS) remained unchanged. Conclusion: The most frequent complaints were hypotonia and feeding difficulty at first presentation. Obesity was the initial finding in 44.2%. GH treatment was started in less than half of the patients. While GH treatment significantly increased height SDS, BMI SDS remained unchanged, possibly due to the relatively older age at GH start.

Loss-of-function variants in SEMA3F and PLXNA3 encoding semaphorin-3F and its receptor plexin-A3 respectively cause idiopathic hypogonadotropic hypogonadism.

PURPOSE: Idiopathic hypogonadotropic hypogonadism (IHH) is characterized by absent puberty and subsequent infertility due to gonadotropin-releasing hormone (GnRH) deficiency. IHH can be accompanied by normal or compromised olfaction (Kallmann syndrome). Several semaphorins are known potent modulators of GnRH, olfactory, and vomeronasal system development. In this study, we investigated the role of Semaphorin-3F signaling in the etiology of IHH. METHODS: We screened 216 IHH patients by exome sequencing. We transiently transfected HEK293T cells with plasmids encoding wild type (WT) or corresponding variants to investigate the functional consequences. We performed fluorescent IHC to assess SEMA3F and PLXNA3 expression both in the nasal region and at the nasal/forebrain junction during the early human fetal development. RESULTS: We identified ten rare missense variants in SEMA3F and PLXNA3 in 15 patients from 11 independent families. Most of these variants were predicted to be deleterious by functional assays. SEMA3F and PLXNA3 are both expressed along the olfactory nerve and intracranial projection of the vomeronasal nerve/terminal nerve. PLXNA1-A3 are expressed in the early migratory GnRH neurons. CONCLUSION: SEMA3F signaling through PLXNA1-A3 is involved in the guidance of GnRH neurons and of olfactory and vomeronasal nerve fibers in humans. Overall, our findings suggest that Semaphorin-3F signaling insufficiency contributes to the pathogenesis of IHH.

Hypogonadism: Is It Always Hypogonadotropic in an Adolescent With a Cleft Palate? A Surprising Case of Klinefelter Syndrome.

Pituitary hormone deficiencies may occur in children with midline defects; in these cases, hypogonadism is usually hypogonadotropic. Herein, we report a boy at the age of 13.8 years with mild mental retardation, previously operated for complete cleft palate (isolated) and presented with hypoglycemia due to isolated secondary adrenal insufficiency, who further had a decrease in testicular size with increased follicle-stimulating hormone level (hypergonadotropic hypogonadism) and diagnosed with Klinefelter syndrome. Klinefelter syndrome in childhood is rarely diagnosed and cases are observed in a wide spectrum. Although some regional duplications of the X chromosome also show midline defects such as spina bifida-neural tube defects, mental retardation, hypopituitarism (mostly growth hormone deficiency); coexistence of Klinefelter syndrome and isolated secondary adrenal deficiency/midline defect in our case may also be coincidental. However, to our knowledge, this is the first case in literature with this association in a patient with a 47, XXY karyotype.

Is Waist-height Ratio Associated with Thyroid Antibody Levels in Children with Obesity?

Objective: Obesity is known to affect thyroid function. Recently, waist-height ratio (WHtR) has been considered as a useful marker of subclinical hypothyroidism in obese cases, but its relation with thyroid autoimmunity still remains unclear. We evaluated the effect of body fat mass, WHtR, and metabolic parameters on thyroid autoantibody levels in children with obesity. Methods: This was a cross-sectional study carried out with an obese [n=56, male/female (M/F): 29/26] and a healthy group (n=38, M/F: 19/19). All subjects underwent anthropometric measurements, laboratory investigations for thyroid function tests, thyroid peroxidase (TPO-ab) and thyroglobulin-antibodies (Tg-ab), transaminases, blood glucose, insulin levels, and lipids after overnight fasting; homeostatic model assessment for insulin resistance (HOMA-IR) was calculated for assessment of insulin resistance. Fat mass was estimated by multiple frequency bioimpedance analysis in the obese group, which was further divided into two subgroups according to the median of WHtR. All parameters were compared between the groups/subgroups. Results: In the obese group, weight, height, body mass index (BMI), free triiodothyronine, thyrotropin, TPO-ab, insulin, low density lipoprotein-cholesterol, total cholesterol, alanine aminotransferase levels, and HOMA-IR were significantly higher than the controls group (p<0.05 for all). Median of WHtR was 0.6 in the obese group. In the "WHtR >0.6" subgroup (n=28), weight, BMI, fat mass, TPO-ab, Tg-ab, insulin and triglyceride levels were higher than WHtR ≤0.6 subgroup (p<0.05). A positive correlation was obtained between Tg-ab and WHtR (rho=0.28, p=0.041). Conclusion: Euthyroid children with obesity and a WHtR >0.6 are likely to have higher thyroid antibody levels, and Tg-ab levels have a positive correlation with WHtR, which reveals an association of central adiposity with thyroid autoantibody levels in these cases.

Clinical and Genetic Characteristics of Patients with Corticosterone Methyloxidase Deficiency Type 2: Novel Mutations in CYP11B2

Corticosterone methyloxidase deficiency type 2 is an autosomal recessive disorder presenting with salt loss and failure to thrive in early childhood and is caused by inactivating mutations of the CYP11B2 gene. Herein, we describe four Turkish patients from two families who had clinical and hormonal features compatible with corticosterone methyloxidase deficiency and all had inherited novel CYP11B2 variants. All of the patients presented with vomiting, failure to thrive and severe dehydration, except one patient with only failure to thrive. Biochemical studies showed hyponatremia, hyperkalemia and acidosis. All patients had normal cortisol response to adrenocorticotropic hormone stimulation test and had elevated plasma renin activity with low aldosterone levels. Three patients from the same family were found to harbor a novel homozygous variant c.1175T>C (p.Leu392Pro) and a known homozygous variant c.788T>A (p.Ile263Asn) in the CYP11B2 gene. The fourth patient had a novel homozygous variant c.666_667delCT (p.Phe223ProfsTer35) in the CYP11B2 gene which caused a frame shift, forming a stop codon. Corticosterone methyloxidase deficiency should be considered as a differential diagnosis in patients presenting with hyponatremia, hyperkalemia and growth retardation, and it should not be forgotten that this condition is life-threatening if untreated. Genetic analyses are helpful in diagnosis of the patients and their relatives. Family screening is important for an early diagnosis and treatment. In our cases, previously unreported novel variants were identified which are likely to be associated with the disease.

Lipid accumulation product is a predictor of nonalcoholic fatty liver disease in childhood obesity.

BACKGROUND: Lipid accumulation product (LAP) is associated with the presence and severity of nonalcoholic fatty liver disease (NAFLD) in adults. PURPOSE: Here we evaluated the ability of LAP to predict NAFLD in obese children. METHODS: Eighty obese children (38 girls; age 6-18 years) were included. Anthropometric measurements and biochemical values were obtained from the patients' medical records. LAP was calculated as [waist circumference (WC) (cm) - 58]×triglycerides (mmol/L) in girls; [WC (cm) - 65]×triglycerides (mmol/ L) in boys. The minLAP and adjLAP were described (3% and 50% of WC values, respectively) and the total/high-density lipoprotein cholesterol index (TC/HDL-C) was calculated. NAFLD was observed on ultrasound, and patients were divided into 3 groups by steatosis grade (normal, grade 0; mild, grade 1; moderate-severe, grade 2-3). The area under the curve (AUC) and appropriate index cutoff points were calculated by receiver operator characteristic analysis. RESULTS: LAP was positively correlated with puberty stage (rho=0.409; P<0.001), fasting insulin (rho= 0.507; P<0.001), homeostasis model assessment of insulin resistance (rho=0.470; P<0.001), uric acid (rho=0.522; P<0.001), and TC/HDL-C (rho=0.494; P<0.001) and negatively correlated with HDL-C (rho=-3.833; P<0.001). LAP values could be used to diagnose hepatosteatosis (AUC=0.698; P=0.002). The LAP, adjLAP, and minLAP cutoff values were 42.7 (P=0.002), 40.05 (P=0.003), and 53.47 (P= 0.08), respectively. For LAP, the differences between the normal and mild groups (P=0.035) and the normal and moderate-severe groups were statistically significant (P=0.037), whereas the difference between the mild and moderate-severe groups was not (P>0.005). There was a statistically significant difference between the normal and mild groups for adjLAP (P=0.043) but not between the other groups (P>0.005). There was no significant intergroup difference in minLAP (P>0.005). CONCLUSION: LAP is a powerful and easy tool to predict NAFLD in childhood. If LAP is ≥42.7, NAFLD should be suspected. This is the first study to assess LAP diagnostic accuracy for childhood obesity.

Management of Thyrotoxicosis in Children and Adolescents: A Turkish Multi-center Experience

Objective: To determine the demographic and biochemical features of childhood and juvenile thyrotoxicosis and treatment outcome. Methods: We reviewed the records of children from 22 centers in Turkey who were diagnosed with thyrotoxicosis between 2007 to 2017. Results: A total of 503 children had been diagnosed with thyrotoxicosis at the centers during the study period. Of these, 375 (74.6%) had been diagnosed with Graves' disease (GD), 75 (14.9%) with hashitoxicosis and 53 (10.5%) with other less common causes of thyrotoxicosis. The most common presenting features in children with GD or hashitoxicosis were tachycardia and/or palpitations, weight loss and excessive sweating. The cumulative remission rate was 17.6% in 370 patients with GD who had received anti-thyroid drugs (ATDs) for initial treatment. The median (range) treatment period was 22.8 (0.3-127) months. No variables predictive of achieving remission were identified. Twenty-seven received second-line treatment because of poor disease control and/or adverse events associated with ATDs. Total thyroidectomy was performed in 17 patients with no recurrence of thyrotoxicosis and all became hypothyroid. Ten patients received radioiodine and six became hypothyroid, one remained hyperthyroid and restarted ATDs and one patient achieved remission. Two patients were lost to follow up. Conclusion: This study has demonstrated that using ATDs is the generally accepted first-line approach and there seems to be low remission rate with ATDs in pediatric GD patients in Turkey.

Effective sociodemographic and clinical factors in weight loss in childhood obesity.

AIM: Obesity is a more common and important health problem in childhood. We aimed to determine sociodemographic and clinical factors contributing weight loss. MATERIAL AND METHODS: Medical records of 120 obese patients (6-18 years old) applied at least twice for follow-up between 2012 (January)-2016 (September) were reviewed. Age, gender, socioeconomic status, family obesity, comorbidities, medications, operations, exercise frequency, screen time, physical examination findings and biochemical/hormone values [thyroid hormone, fasting insulin/glucose, cholesterol levels, Homeostasis model assesment insulin resistance (HOMA-IR), oral glucose tolerance test results (if applied) were recorded. Patients with a difference between the initial and last body mass index standart deviation higher than -0.2 were defined as "the good losing weight" group; the rest as "the poorly losing weight" group. The SPSS 22.0 program was used for analyzes. RESULTS: Puberty stage showed a significant difference (p=0,019); 65% of patients in the poorly losing weight group but 54% of other group were at stage 4-5. The initial body mass index standart deviation and exercise frequency were higher in the good losing weight group, the last measured body mass index standart deviation was lower (p=0). In the other group, baseline HOMA-IR was higher (p=0.037); there were more metformin-initiated patients but the difference was not significant. CONCLUSION: We observed that exercise frequency was higher in cases with good weight loss; therefore, we consider that increasing physical activity is an important step. Other crucial outcomes are that the initial body mass index standart deviation is higher while HOMA-IR is lower in those cases and that puberty stage is higher in poorly weight losing patients.

Incidence of Type 1 Diabetes in Children Aged Below 18 Years during 2013-2015 in Northwest Turkey

Objective: To assess the incidence of type 1 diabetes mellitus (T1DM) in children under 18 years of age in the northwest region of Turkey during 2013-2015. Methods: All newly diagnosed T1DM cases were recorded prospectively during 2013-2015. Total, as well as gender and age group specific (0-4, 5-9, 10-14 and 15-17 age) mean incidences per 100,000 per year were calculated. Results: There were 1,773 patients diagnosed during 2013-2015 (588 cases in 2013, 592 cases in 2014, 593 cases in 2015). Of these, 862 (48.6%) were girls and 911 (51.4%) were boys. The mean age at diagnosis was 9.2±4.2 years and it was not significantly different between girls (9.0±4.1 years) and boys (9.4±4.4 years) (p=0.052). The crude mean incidence was 8.99/100.000 confidence interval (CI) (95% CI: 8.58-9.42). Although mean incidence was similar between boys [8.98/100.000 (CI: 8.40 to 9.58)] and girls [9.01/100.000 (CI: 8.42 to 9.63)], there was male predominance in all groups except for 5-9 year age group. The standardized mean incidence was 9.02/100.000 according to the World Health Organization standard population. The mean incidence for the 0-4, 5-9, 10-14 and 15-17 age groups was 6.13, 11.68, 11.7 and 5.04/100.000 respectively. The incidence of T1DM was similar over the course of three years (p=0.95). A significant increase in the proportion of cases diagnosed was observed in the autumn-winter seasons. Conclusion: The northwest region of Turkey experienced an intermediate incidence of T1DM over the period of the study.

Neonatal Diabetes: Two Cases with Isolated Pancreas Agenesis due to Homozygous PTF1A Enhancer Mutations and One with Developmental Delay, Epilepsy, and Neonatal Diabetes Syndrome due to KCNJ11 Mutation

Neonatal diabetes mellitus is a rare form of monogenic diabetes which is diagnosed in the first six months of life. Here we report three patients with neonatal diabetes; two with isolated pancreas agenesis due to mutations in the pancreas-specific transcription factor 1A (PTF1A) enhancer and one with developmental delay, epilepsy, and neonatal diabetes (DEND) syndrome, due to a KCNJ11 mutation. The two cases with mutations in the distal enhancer of PTF1A had a homozygous g.23508363A>G and a homozygous g.23508437A>G mutation respectively. Previous functional analyses showed that these mutations can decrease expression of PTF1A which is involved in pancreas development. Both patients were born small for gestational age to consanguineous parents. Both were treated with insulin and pancreatic enzymes. One of these patients' fathers was also homozygous for the PTF1A mutation, whilst his partner and the parents of the other patient were heterozygous carriers. In the case with DEND sydrome, a previosly reported heterozygous KCNJ11 mutation, p.Cys166Tyr (c.497G>A), was identified. This patient was born to nonconsanguineous parents with normal birth weight. The majority of neonatal diabetes patients with KCNJ11 mutations will respond to sulphonylurea treatment. Therefore Glibenclamide, an oral antidiabetic of the sulphonylurea group, was started. This treatment regimen relatively improved blood glucose levels and neurological symptoms in the short term. Because we could not follow the patient in the long term, we are not able to draw conclusions about the efficacy of the treatment. Although neonatal diabetes mellitus can be diagnosed clinically, genetic analysis is important since it is a guide for the treatment and for prognosis.

Evaluation of Adenovirus-36 (Ad-36) antibody seropositivity and adipokine levels in obese children.

Adenovirus 36 (Ad-36) has recently been suggested as a possible contributor to the current obesity epidemic. The aim of this study was to investigate the prevalence of Ad-36 antibodies in obese children, as well as investigate the role of serum leptin and lipid levels in Ad-36-obesity. Seventy-one obese children and 62 non-obese children were included as the patient group (PG), including the healthy control group (HCG), respectively. Simultaneously, Ad-36 antibodies and adipokine levels were assessed with serum neutralization assays (SNA) and ELISA. Ad-36 antibody was detected in 9 patients (12.7%) and 1 patient (1.6%) in both the PG and HCG, respectively, while a significant difference was detected between groups (p < 0.05). Although serum LDL, total cholesterol, triglycerides and leptin levels were detected significantly higher, adiponectin level was detected paradoxically lower in the PG. However, a significant difference was not detected for lipids and leptin levels; adiponectin levels were found to be significantly lower in Ad-36 antibody-positive PG (p < 0.05). In conclusion, we suggest there is an association between Ad-36 and obesity in children, including IL-6 levels increasing in obese children with Ad-36 seropositivity. Conversely, adiponectin levels in obese children with Ad-36 seropositivity were higher. As such, there is a need for studies to understand the mechanisms underlying this observation.

A Case of Vitamin D-Dependent Rickets Type 1A with a Novel Mutation in the Uzbek Population.

Vitamin D-dependent rickets type 1A (VDDR-1A) (Online Mendelian Inheritance in Man #264700) is a rare, autosomal recessively inherited disorder due to inactivating mutations in CYP27B1. It is characterized by early onset of rickets with hypocalcemia. We aimed to describe the clinical and laboratory findings in a VDDR-1A case and to report a novel homozygote truncating mutation NM_000785.3 c.403C>T (p.Q135*) in CYP27B1 which to our knowledge is the first described mutation in the Uzbek population. The patient was admitted with tetany at the age of 12 months. He was a healthy Uzbek boy until 9 months of age when he had a seizure due to hypocalcemia. Vitamin D treatment was given orally in Turkmenistan (no data available for dose and duration). The patient was the product of a consanguineous marriage. His brother had died with hypocalcemia and pneumonia. At physical examination, anthropometric measurements were within normal limits; he had caput quadratum, enlarged wrists, and carpopedal spasm. Blood calcium, phosphorus, alkaline phosphatase, and parathormone (PTH) levels were 5.9 mg/dL, 3.5 mg/dL, 987 IU/L, and 182.8 pg/mL (12-72), respectively. Radiological findings included cupping and fraying of the radial and ulnar metaphyses. Renal ultrasound revealed nephrocalcinosis (grade 1). Despite high serum PTH and 25-hydroxyvitamin D3 levels, 1,25-dihydroxyvitamin D3 level was low, suggesting a diagnosis of VDDR-1A. The patient was treated with calcium carbonate and calcitriol. DNA sequencing revealed a novel homozygous mutation of NM_000785.3 c.403C>T (p.Q135*) in CYP27B1. VDDR-1A is a rare disorder which needs to be considered even in countries where nutritional vitamin D deficiency is still common.

General health status and intelligence scores of children of mothers with acromegaly do not differ from those of healthy mothers.

PURPOSE: To determine the physical status and intelligence scores of children of acromegalic mothers and to compare them with those of children from mothers without acromegaly. METHODS: Six women with acromegaly who became pregnant under follow-up between 2010 and 2014 and their 16 children (group A) were assessed and compared with 16 children of healthy women (group B) and 15 children of women with prolactinoma (group C). The physical examinations of children were performed by the department of pediatric endocrinology and intelligence quotient (IQ) testing was undertaken by adult and pediatric psychiatry departments, using appropriate scales for their ages. RESULTS: Six of the 16 children (girls/boys: 7/9) were born after the diagnosis of acromegaly. Five of the 6 pregnancies occured when the patients were taking somatostatin analogs, none continued taking the drugs during pregnancy. The mean IQ of groups A, B, and C were 106.4 ± 12.5, 105.3 ± 12.5, and 103.2 ± 16.1 respectively (p > 0.05). The mean ages, birth percentiles, recent weight and height standard deviation scores were similar between groups (p > 0.05). Two siblings from group A and 1 child from group B were large for gestational age at birth. At recent follow-up, two children from group A were found tall for their age and one from group C was short for his age and was placed under the care of pediatric endocrinology clinic. CONCLUSIONS: Pregnancies in acromegaly seems to be uneventful and the general health status and IQ scores of children from women with and without acromegaly were found similar.