Objective: To assess the acute effects of blood transfusion on insulin sensitivity and pancreatic ß-cell function in thalassemia patients.
Methods: Fifty children and adolescents with ß-thalassemia/HbE disease were enrolled in a prospective cohort study. Hemoglobin, serum ferritin and oral glucose tolerance test (OGTT) were performed prior to, and one week after blood transfusion. Insulin sensitivity indices [homeostatic model assessment (HOMA) of insulin resistance (HOMA-IR), whole body insulin sensitivity index (WBISI)] and ß-cell function indices [HOMA of ß-cell function (HOMA-ß), insulinogenic index (IGI), and disposition index (DI)] were calculated from glucose and insulin levels obtained during the OGTT.
Results: Following blood transfusion, hemoglobin and serum ferritin increased significantly; 8.5 to 10.1 g/dL (p<0.001) and 1764 to 2160 ng/mL (p<0.001), respectively. ß-Cell function indices also increased significantly [median HOMA-ß: 74.3 vs. 82.7 (p=0.033); median IGI: 59.6 vs. 79.3 (p=0.003); median DI: 658 vs. 794 (p=0.01)]. However, the insulin sensitivity index (WBISI) tended to decrease and the insulin resistance index (HOMA-IR) tended to increase although this did not reach significance. Multivariate analysis showed that pre-transfusion serum ferritin was the major factor negatively associated with WBISI and positively associated with HOMA-IR, but pre-transfusion hemoglobin had no significant association with insulin sensitivity indices post-transfusion.
Conclusion: This study demonstrated that acute increases in serum ferritin and hemoglobin following blood transfusion in patients with thalassemia might contribute to an increase in insulin secretion and to a trend towards increased insulin resistance.

Objective: Nesfatin-1, an anorexigenic neuropeptide, is expressed mainly in the central nervous system and in some peripheral tissues. The role of nesfatin-1 in energy balance has been investigated. Despite the suggestion of a role for nesfatin-1 in reproductive function, data are limited on the role of nesfatin-1 in human puberty.
Methods: The aim of this study was to investigate the following: i) the role of nesfatin-1 in puberty, and ii) relationship between nesfatin-1 and anthropometric measurements and gonadotropin levels in girls with idiopathic central precocious puberty (CPP). Twenty-four girls with CPP (7.68±1.02 years) and 20 female, prepubertal, healthy controls (7.48±0.88 years) were enrolled in the study. All patients with CPP were treated by the intramuscular administration of leuprolide acetate at a daily dose of 3.75 mg for 28 days. Nesfatin-1 was measured before and during treatment.
Results:
There was no difference in serum nesfatin-1 levels in girls with CPP and healthy controls [5.67 (2.5-20.6) mmol/L and 5.75 (2.51-9.64) mmol/L], respectively. There was a negative correlation between nesfatin-1 levels and body weight and body mass index-standard deviation score (p=0.01, r=-0.83; p=0.025, r=-0.81, respectively). No correlation was found between nesfatin-1 and gonadotropin, estradiol levels, uterine length or endometrial thickness.
Conclusion: The results of this study suggest that there are no differences between girls with CPP and healthy, prepubertal girls regarding nesfatin-1 levels.

Objective: Obesity affects almost all systems in the body. This includes the retinal nerve fibers which may be damaged due to a chronic inflammatory process. To determine changes in retinal nerve fiber layer (RNFL) thickness in non-diabetic children and adolescents using optical coherence tomography (OCT) and to evaluate the relationship between this change, metabolic risk factors and pubertal stage.
Methods: Thirty-eight obese and 40 healthy children and adolescents aged 10-18 years were included in the study. RNFL measurements from the optic disk and all surrounding quadrants were obtained using OCT from both eyes of the individuals in the study groups. Correlations between RNFL thickness and age, auxological measurements, pubertal stage, systolic and diastolic blood pressure, homeostasis model assessment-insulin resistance (HOMA-IR) index and lipid values were investigated.
Results: A general decrease was observed in RNFL thickness in obese subjects compared to the controls, the decrease being highest in the inferior quadrant, although these differences were not statistically significant (p>0.05). RNFL thickness was negatively correlated with body mass index (BMI) standard deviation score (SDS) in both groups (control group r=-0.345, p=0.029; obese group r=-0.355, p=0.022). Significant negative correlations were determined between diastolic blood pressure, HOMA-IR, low density lipoprotein cholesterol level and RNFL thickness (r=-0.366, p=0.024; r=-0.394, p=0.016; and r=-0.374, p=0.022, respectively) in the obese group, while there was no association between these parameters and RNFL thickness in the control group.
Conclusion: In this cross-sectional study, no statistically significant difference in RNFL thicknesses between the obese and control groups was determined. However, RNFL thickness was found to decrease in both healthy and obese children as BMI-SDS values increased. Further prospective studies may be of benefit to determine whether the decrease in RNFL values might become more pronounced on long-term follow-up.

Objective: Hypophosphatasia (HPP) is an inborn error of metabolism with significant morbidity and mortality. Its presentation is nonspecific leading to delayed or missed diagnosis. Low alkaline phosphatase (ALP) is a diagnostic test. Unlike high ALP, low level is commonly not flagged by laboratories as abnormal. A new treatment was shown to be effective in HPP. In this study we aimed to establish the frequency of low ALP levels requiring notification to physicians by the laboratory and also to describe the clinical manifestations of patients presenting with low ALP for a possible diagnosis of HPP.
Methods: Patients under age 18 years with low ALP levels were identified from biochemistry records over a period of 6 months. Reference ranges were used as per the Associated Regional and University Pathologists Reference Laboratory (Utah, USA). Electronic results for patients with low levels were checked for flagging as abnormal/low ALP results. Charts of identified patients were reviewed. Presenting features were categorized under groups of disorders.
Results: ALP levels were tested in 2890 patients. 702 had values less than 160 U/L. Of these patients, 226 (32%) had age/gender specific low ALP. None of the low ALP results was flagged as low. Twenty-one had more than one low reading and their charts were reviewed. Four patients in the neuromuscular and four in the miscellaneous group presented with features consistent with HPP despite these patients having no specific diagnoses.
Conclusion: Laboratories do not alert physicians in cases with low ALP levels. A persistently low level in patients with unspecified diagnoses could be a key to diagnose HPP. Implementing lab-specific ranges and alerting for low levels could prompt physicians to investigate for undiagnosed HPP.

Objective: To estimate the relationship between cord blood bisphenol A (BPA) levels and anogenital measurements in healthy newborns.
Methods: Pregnancy and birth history, together with body mass and length data, anogenital measurements, penile measurements and cord blood samples were obtained from healthy newborns. Cord blood concentration of BPA was analyzed by sandwich enzyme-linked immunosorbent assays kit.
Results: Among 130 healthy newborns (72 boys, 58 girls), mean anopenile distance was 45.2±6 mm and anoscrotal distance was 21.9±5.4 mm in boys; mean anoclitoral distance was 33.8±6.6 mm and mean anofourchette distance was 12.2±4.9 mm in girls. Mean cord blood BPA level was 4.75±2.18 ng/mL. 90th percentile value for cord blood BPA was 8.26 ng/mL and the analysis showed a statistically significant correlation between anoscrotal distance and cord blood BPA levels above the 90th percentile (p=0.047) in boys. The changes in anogenital distance in girls were not statistically significant.
Conclusion: We showed a significant association between high cord blood BPA levels and shortened anoscrotal distance in male newborns. However, this result should be interpreted with caution since there were no significant external genital abnormalities in our study group.

Objective: Y-chromosome gonadal dysgenesis (GD) is a rare subgroup of disorders of sexual development (DSD) which results from underdeveloped testis and may exhibit heterogenous symptoms. These patients are phenotypically classified into two groups - complete and partial, and their karyotypic description is either 46,XY GD or 45,X/46,XY GD. In this study; we aimed to evaluate the characteristics of cases with Y-chromosome GD.
Methods: Thirty eight cases were followed-up between 1998 and 2016. The age of admission ranged between 0 and 17 years. Clinical and laboratory findings as well as follow-up characteristics of the cases were evaluated retrospectively from the patient files.
Results: There were 26 cases (four complete, 22 partial) in the 46,XY GD group, and 12 cases (four complete, 8 patients with complete GD in the 45,X/46,XY. Mean age at admission was 6.2±4.6 years for all cases. Patients with complete GD in the 45,X/46,XY GD group were diagnosed earlier that the patients with complete GD in the 46,XY group [11 years vs. 14.31 years of age (p<0.01)]. There were no additional findings in 55% of all patients. In the remaining 45% additional clinical findings, mainly short stature, were detected in 75% of the patients in the 45,X/46,XY GD and 30% of the patients in the 46,XY GD groups. All patients with complete 46,XY and 45,X/46,XY GD were raised as females. There was no gender dysphoria in patients that were raised as females, except for one case. Gonadectomy was performed in 14 patients, at a mean age of 8.75±2.3 years and pathological assessment of the gonads was reported as normal in all cases.
Conclusion: Y-chromosome GD is a very heterogenous clinical and genetic disorder and requires a multifaceted approach to management. Whether including syndromic features or not, associated clinical features may lead to earlier diagnosis, especially in complete forms of GD. Due to difficulties encountered in the long-term follow-up of these patients, evaluation of appropriateness of sex of rearing decision is not truly possible. Performance of gonadectomy during the first decade appears be a preventive factor for tumor development since these tumors are usually seen during the second decade.

Objective: To evaluate the effect of intrahepatic cholestasis of pregnancy (ICP) on neonatal birth weight.
Methods: Potential articles were identified by searching PubMed and Web of Science databases on April 30th, 2017. Using the Mantel-Haenszel random-effects or fixed-effects model, outcomes were summarized through weighted mean difference (WMD) and 95% confidence intervals (CI). Potential publication bias was tested using a funnel plot and the methods of Egger’s regression and Begg’s test.
Results: A total of eight studies were included in our meta-analysis. Six studies reported data on neonatal birth weight in ICP and control pregnancies. Pooled data from the six studies showed that the birth weight in the ICP group was significantly lighter than in the control group. The overall pooled WMD was -175 g (95% CI: -301, -48). Meanwhile, pooled data from the other two studies indicated that the birth weight in the late-onset ICP group was heavier than in the early-onset ICP group (WMD: 267 g, 95% CI: 168, 366).
Conclusion: Neonatal birth weights in ICP pregnancies were lower than in normal pregnancies. Furthermore, early-onset ICP is associated with a lower birth weight than late-onset ICP.

Objective: Vitamin D deficiency is a serious health problem despite a general improvement in socio-economic status in Turkey. The aim of this study was to evaluate maternal vitamin D status and its effect on neonatal vitamin D concentrations after a support programme for pregnant women was introduced. A second aim was to identify risk factors for vitamin D deficiency in a district of Ýstanbul.
Methods: A total of 97 pregnant women and 90 infants were included in this study, conducted between January and October 2016. The demographic data, risk factors and daily vitamin intake were recorded. Serum levels of vitamin D, calcium, phosphorus and alkaline phosphatase in all subjects were measured. The mothers and newborns were divided into groups based on their vitamin D levels. The relationship between vitamin D levels and risk factors was analyzed.
Results: Mean ± standard deviation vitamin D levels for the women and their infants were found to be 14.82±11.45 and 13.16±7.16 ng/mL, respectively. The number of mothers and infants was significantly higher in the deficient group, and their mean vitamin D levels significantly lower (9.02±1.34 and 8.80±1.06 ng/mL, respectively) (p<0.001, p<0.001). Only 14.4% of pregnant women took 1000-1200 IU/day of vitamin D. When the mother groups were evaluated in terms of risk factors, there were significant differences in daily vitamin intake and clothing style (p<0.001 and p<0.001 respectively).
Conclusion: Vitamin D deficiency in pregnant women and their infants is still a serious health problem in Turkey, although a vitamin D support programme during pregnancy has been launched by the department of health.

Objective: As in adults, hypertension is also an important risk factor for cardiovascular disease in children. We aimed to evaluate the effect of sleep duration on blood pressure in normal weight Turkish children aged between 11-17 years.
Methods: This cross-sectional study was conducted in the primary and secondary schools of the two central and ten outlying districts of Kayseri, Turkey. Subjects were 2860 children and adolescents (1385 boys, 1475 girls). Systolic and diastolic blood pressures were measured according to the recommendations of the Fourth Report of the National High Blood Pressure Education Program Working Group on High Blood Pressure in Children and Adolescents. Sleep duration was classified as follows: ?8 hours, 8.1-8.9 hours, 9.0-9.9 hours or ?10 hours.
Results: For short sleeper boys and girls (participants with a sleep duration ?8 h) the prevalence of prehypertension and hypertension was 35.0% and 30.8%, respectively. In univariate binary logistic regression analyses (age-adjusted), each unit increment in sleep duration (hours) in boys and girls, decreased the prehypertension and hypertension risk by 0.89 [odds ratio (OR)] [confidance interval (CI); 0.82-0.98] and 0.88 (OR) (CI; 0.81-0.97), respectively (p<0.05). In multiple binary logistic regression analyses [age- and body mass index (BMI)-adjusted] the location of the school and sleep duration categories were shown to be the most important factors for prehypertension and hypertension in both genders, while household income was the most important factor, only in boys.
Conclusions: A sleep duration ?8 h is an independent risk factor for prehypertension and hypertension in Turkish children aged 11-17 years.

Objective: Obesity in childhood and adolescence is one of the most serious public health problems due to a remarkable increase in prevalence in recent years and its close relationship with non-communicable diseases, such as diabetes and hypertension, resulting in increased adult morbidity and mortality. This study aims to quantify the secular trend in different regions of Turkey from 1990 to 2015 by performing a meta-analysis of childhood and adolescent obesity prevalence studies conducted.
Methods: Uludag University Library Database was searched for relevant articles published prior to March 2017. The heterogeneity of the studies in the meta-analysis was tested by the I2 statistic and Cochran’s Q test. The obesity trend analyses were examined by chi-square trend analysis with respect to five year periods. The statistical significance level was taken as ?=0.05.
Results: A total of 76 papers were initially identified addressing childhood and adolescent obesity in Turkey. Fifty-eight papers were selected for analysis. The prevalence of obesity increased from 0.6% to 7.3% with an 11.6-fold increase between the periods 1990-1995 to 2011-2015. The prevalence of obesity increased in both genders. However, boys were more likely to be obese than girls.
Conclusion: Studies on obesity prevalence in the 5-19 age group in Turkey have gained importance, especially in the 2000s. While a remarkable number of prevalence studies, mostly regional, have been conducted between 2005-2011, a gradual decline was observed thereafter. Further national and population-based surveys on prevalence of obesity in children and adolescents are definitely needed in Turkey.

Proopiomelanocortin (POMC) deficiency is a rare monogenic disorder with early-onset obesity. Investigation of this entity have increased our insight into the important role of the leptin-melanocortin pathway in energy balance. Here, we present a patient with POMC deficiency due to a homozygous c.206delC mutation in the POMC gene. We discuss the pathogenesis of this condition with emphasis on the crosstalk between hypothalamic and peripheral signals in the development of obesity and the POMC-melanocortin 4 receptors system as a target for therapeutic intervention.

17-beta hydroxysteroid dehydrogenase type 3 (17ßHSD-3) enzyme catalyzes the conversion of androstenedione (?4) to testosterone (T) in the testes of the developing fetus, thus playing a crucial role in the differentiation of the gonads and in establishing the male sex phenotype. Any mutation in the encoding gene (HSD17B3) can lead to varying degrees of undervirilization of the affected male, ranging from completely undervirilized external female genitalia to predominantly male with micropenis and hypospadias. We present here an infant who was referred to our clinic because of ambiguous genitalia at birth. Gonads were palpable in the inguinal canal bilaterally and no Müllerian structures were identified on pelvic ultrasound. Because of a low T/?4 ratio after a human chorionic gonadotropin stimulation test, a tentative diagnosis of 17ßHSD-3 deficiency was made which was confirmed after genetic analysis of the HSD17B3 gene of the patient. The molecular analysis identified compound heterozygosity of two previously described mutations and could offer some further validation for the idea of a founder effect for 655-1;G›A mutation in the Greek population.

Klinefelter syndrome is the most frequent chromosomal aneuploidy in males occurring in about 1 in 660 males. Epidemiological studies have demonstrated increased risk of type 1 diabetes and type 2 diabetes in adults with Klinefelter syndrome. There is only one previous report of neonatal diabetes in a patient with Klinefelter syndrome. We report transient neonatal diabetes due to a pathogenic heterozygous variant in KCNJ11 in a male infant with Klinefelter syndrome. A 78-day old male infant was noted to have sustained hyperglycemia with serum glucose ranging between 148 mg/dL (8.2 mmol/L) and 381 mg/dL (21.2 mmol/L) three days after undergoing a complete repair of an atrioventricular defect. Hemoglobin A1c was 6.6%. The patient was born at term with a birth weight of 2.16 kg following a pregnancy complicated by gestational diabetes that was controlled with diet. The patient was initially started on a continuous intravenous insulin drip and subsequently placed on subcutaneous insulin (glargine, human isophane and regular insulin). Insulin was gradually decreased and eventually discontinued at seven months of age. Chromosomal microarray at 11 weeks of age showed XXY and a panel-based, molecular test for neonatal diabetes revealed a pathogenic heterozygous variant c.685G>A (p.Glu229Lys) in KCNJ11. The patient is now 34 months old and continues to have normal fasting and post-prandial glucose and HbA1C levels. The patient will need prospective follow up for assessment of his glycemic status. To our knowledge this is the second reported case of neonatal diabetes in an infant with Klinefelter syndrome and the first due to a mutation in the KCNJ11 in a patient with Klinefelter syndrome.

Idiopathic infantile hypercalcemia (IIH) was associated with vitamin-D supplementation in the 1950’s. Fifty years later, mutations in the CYP241A gene, involved in the degradation of vitamin-D, have been identified as being a part of the etiology. We report a case of a 21-month old girl, initially hospitalized due to excessive consumption of water and behavioral difficulties. Blood tests showed hypercalcemia and borderline high vitamin-D levels. Renal ultrasound revealed medullary nephrocalcinosis. An abnormality in vitamin-D metabolism was suspected and genetic testing was performed. This revealed the patient to be compound heterozygous for a common (p.E143del) and a novel (likely) disease-causing mutation (p.H83D) in the CYP24A1 gene. The hypercalcemia normalized following a calcium depleted diet and discontinuation of vitamin-D supplementation. Increased awareness of the typical symptoms of hypercalcemia, such as anorexia, polydipsia, vomiting and failure to thrive, is of utmost importance in diagnosing IHH early and preventing long-term complications such as nephrocalcinosis. Further identification of as many disease-causing mutations in the CYP24A1 gene as possible can help identification of predisposed individuals in whom vitamin-D supplementation should be reconsidered.

Patients with complete XY gonadal dysgenesis (GD) show a high predisposition to germ cell tumors (GCT). Patients with coexistence of GCT and GD have been reported previously. Here we present a 15-year-old girl with mixed GCT and GD who also developed an intra-abdominal synovial sarcoma one year after the treatment. This is the first report, to our knowledge, of synovial sarcoma associated with XY GD.