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Laron syndrome (LS) is a rare disorder leading to short stature as a result of growth hormone (GH) insensitivity. It is caused by mutations in GH receptor gene and characterized by post-natal growth retardation, craniofacial abnormalities, high serum GH and low insulin-like growth factor-I (IGF-I) levels. Several different genetic mutations have been documented up to date. In this article, a patient with LS is reported. A 2-year-old female patient was admitted to the hospital with the complaint of short stature. Her height and weight was 71.7 cm [

Pseudohypoparathyroidism (PHP) is a heterogeneous group of disorder with parathormone target organ resistance, characterized by hypocalcemia, hyperphosphatemia and high blood parathormone (PTH). Typical phenotypic symptoms and additional hormonal resistance can be observed in type Ia, which is also known as Albright hereditary osteodystrophy. Our patient was an eight-year and nine-month old girl with typical Albright-s hereditary osteodystrophy phenotype including short stature, obesity, round face, low nasal bridge, shortened metacarpals, and mild mental retardation. In her biochemical examination, high PTH level and hypothyroidism is detected in spite of normal calcium and phosphor levels. As a result of clinic and laboratory tests, the findings were consistent with PHP type Ia with normocalcemia. In her guanine nucleotide binding protein (G protein), alpha stimulating activity polypeptide 1 (GNAS 1) gene serial analysis, C-308T>C (p1103T) transformation was detected, which was previously reported in a PHP type Ia patient. In this report, we-ve aimed to emphasize the fact that calcium and phosphor level in the blood of the patient with PHP type Ia can be measured normal.

Objective: To determine the growth reference value of children in our province and to compare these values with current values of the USA and other local values of our country.

Aim The exact mechanisms that trigger the onset of puberty are not well known. Adipomyokines are postulated to stimulate the central neural network. In the present study, we investigated irisin levels in girls with central precocious puberty (CPP), slowly progressing precocious puberty (SPPP), or premature thelarche (PT); we also studied prepubertal girls and to determine if this adipomyokine could be used as a marker in this context. Methods A total of 94 girls including 33 with CPP, 31 with precocious puberty (PP) variants (SPPP or PT), and 30 healthy controls were enrolled to the study. The mean irisin levels were compared between groups. The bivariate correlations of irisin levels with clinical and laboratory parameters were assessed. Multivariate linear regression analysis was performed to determine independent predictive factors of irisin levels. Results Irisin levels were higher in the CPP group compared with the other groups (CPP group: 723.25 ± 62.35 ng/mL; PP variants group: 529.60 ± 39.66 ng/mL; and control group: 325.03 ± 27.53 ng/mL) (P Conclusions The mean irisin levels were higher in patients with CPP compared with other groups. The results of this study imply that increased irisin levels may be used as a marker of CPP provided that these findings are confirmed in larger prospective studies.

Background Cytochrome P450 Oxidoreductase (POR) deficiency is one of the rare forms of adrenal insufficiency. It causes suspicious genitalia in boys. The disorder in steroid synthesis carries the symptoms of both 21-hydroxylase and 17–20-lyase deficiency. Cortisol deficiency is not frequent, but the stress response is impaired. Case An 8-month-old male patient was admitted to our hospital with vomiting for 15 days. Hyponatremia and hyperkalemia were detected in the first laboratory tests of the patient and he was hospitalized for further investigation. In the background: The patient was born at term by caesarean section. His birth weight was 3600 grams, developmental stages were normal and he had no hospitalization before. Family history; the parents were healthy and they were unrelated. Physical examination; Height: 65 cm (-2,23 SDS; Results The patient is considered to have POR deficiency and his genetic research is in progress. Hydrocortisone 15 mg/m2/day and fludrocortisone 0.1 mg/day were prescribed. We presented this case for discussing POR deficiency as a cause of rare adrenal insufficiency.

Background Adipokines have been suggested to play an important role in the pathogenesis of polycystic ovarian syndrome (PCOS). Omentin is an adipokine secreted essentially by visceral adipose tissue with an insulin-sensitizing effect. Insulin resistance (IR) is a common feature of PCOS, therefore the aim of this study was to investigate omentin-1 level in adolescent girls with PCOS and its relationship with IR and androgens. Method A total of 41 obese girls with PCOS, and 30 age- and body mass index (BMI)-matched obese girls without PCOS were enrolled in the study. The demographic, clinic and laboratory characteristics of the groups were compared. Additionally, bivariate correlation analysis of omentin-1 with BMI standard deviation score (BMI-SDS), insulin, glucose, homeostatic model assessment of IR (HOMA-IR), total and free testosterone was performed. Results In the PCOS group HOMA-IR, free and total testosterone were higher than in the control group. Omentin-1 was lower in the PCOS group compared with the controls (55.01 ± 7.99 ng/mL vs 59.10 ± 7.02 ng/mL, respectively; P = 0.027). Omentin-1 was inversely correlated with free testosterone (r = -0.527, P = 0.030) and BMI-SDS (r = -0.241, P = 0.046) but it was not correlated with total testosterone, HOMA-IR, glucose, insulin or serum lipids. Conclusion Omentin-1 was lower in obese girls with PCOS and hyperandrogenism was associated with this condition.

ABALI, SAYGIN/0000-0001-6552-2801; Turan, Serap/0000-0002-5172-5402; Hatun, Sukru/0000-0003-1633-9570; Akgun, Abdurrahman/0000-0002-2917-2469; yesiltepe mutlu, gul/0000-0003-3919-7763; Ozgen, Ilker Tolga/0000-0001-6592-9652 WOS: 000451667000006 PubMed: 29789274 Objective: To assess the incidence of type I 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 5.04/1 00.000 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.

Objective: Malnutrition continues to be a leading cause of stunted growth in many countries. This study aimed to investigate serum nesfatin-1 and orexin-A levels in underweight children and the potential correlations of these levels with anthropometric and nutritional parameters. Methods: The study enrolled 44 prepubertal children (between 2 and 12 years of age) with thinness grades of 1-3 and 41 healthy age- and gender-matched children. The demographic, clinical and laboratory parameters including nesfatin-1 and orexin-A concentrations were compared between the two groups. The correlations of nesfatin-1 and orexin-A with biochemical and anthropometric parameters were investigated. The receiver operating characteristic (ROC) analysis were also performed for evaluating nesfatin-1 and orexin-A in distinguishing children with malnutrition from healthy controls. Results: Thyroid-stimulating hormone, vitamin B12 and insulin levels were significantly lower in the study group than controls (p=0.001, p=0.049 and p=0.033, respectively). Mean nesfatin-1 levels in the malnourished group was also significantly lower compared to the healthy controls (3871.2 ± 1608.8 vs. 5515.0 ± 3816.4 pg/mL, p=0.012). No significant difference was observed in the orexin-A levels between the two groups (malnourished vs. control groups: 1135.7 ± 306.0 vs. 1025.7 ± 361.6 pg/mL, p=0.141). Correlation analyses revealed a positive correlation of nesfatin-1 and a negative correlation of orexin-A with body mass index (BMI) z-score. ROC analysis demonstrated that nesfatin-1 and orexin-A cannot be used to distinguish children with malnutrition from healthy controls (AUC: 0.620, p=0.061 for nesfatin-1 and AUC: 0.584, p=0.190 for orexin-A). Conclusion: The positive correlation of nesfatin-1 and the negative correlation of orexin-A with BMI suggest that these neuropeptides may be a part of a protective mechanism in the maintenance of nutritional status and that they may have a role in regulating food intake in undernourished children.

Background/Aims: This study aimed to understand the role of non-alcoholic fatty liver disease (NAFLD) in increasing the risk of atherosclerosis in obese pediatric patients. Materials and Methods: The study included 109 obese children (age, 9-15 years) and a control group comprising 44 healthy age- and gender-matched children with normal weight. NAFLD was diagnosed using conventional ultrasound (US) examination. Both right carotid intima-media thickness (CIMT) and flow-mediated dilation (FMD) were assessed in addition to anthropometric measures and serum biochemical parameters, including lipid profile and fasting glucose and insulin levels. Homeostatic model assessment of insulin resistance (HOMA-IR) was calculated as a measure of insulin resistance. Results: Mean age and gender distributions were similar in the obese children and control group (p=0.168 and p=0.705, respectively). Median body mass index standard deviation scores of obese children with grade II-III NAFLD were significantly higher than those of obese children without hepatosteatosis (p

PubMedID: 25262569 Objective: The spectrum of genetic alterations in cases of hypogonadotropic hypogonadism continue to expand. However, KISS1R mutations remain rare. The aim of this study was to understand the molecular basis of normosmic idiopathic hypogonadotropic hypogonadism. Methods: Clinical characteristics, hormonal studies and genetic analyses of seven cases with idiopathic normosmic hypogonadotropic hypogonadism (nIHH) from three unrelated consanguineous families are presented. Results: One male presented with absence of pubertal onset and required surgery for severe penoscrotal hypospadias and cryptorchidism, while other two males had absence of pubertal onset. Two of four female cases required replacement therapy for pubertal onset and maintenance, whereas the other two had spontaneous pubertal onset but incomplete maturation. In sequence analysis, we identified a novel homozygous nonsense (p.Y323X) mutation (c.C969A) in the last exon of the KISS1R gene in all clinically affected cases. Conclusions: We identified a homozygous nonsense mutation in the KISS1R gene in three unrelated families with nIHH, which enabled us to observe the phenotypic consequences of this rare condition. Escape from nonsense-mediated decay, and thus production of abnormal proteins, may account for the variable severity of the phenotype. Although KISS1R mutations are extremely rare and can cause a heterogeneous phenotype, analysis of the KISS1R gene should be a part of genetic analysis of patients with nIHH, to allow better understanding of phenotype-genotype relationship of KISS1R mutations and the underlying genetic basis of patients with nIHH. © 2014 John Wiley & Sons Ltd.

Background: The objective of this study is to investigate the efficacy of continuous renal replacement therapy (CRRT), mainly continuous venovenous hemodiafiltration (CVVHDF), and evaluate vasoactive requirements in hyperammonemic neonates and infants. Methods: Patients who underwent CRRT for hyperammonemia were retrospectively analyzed. Measurements and Main Results: Patients in 7 of the encounters were treated solely by CVVHDF. During 3 encounters, patients who received continuous venovenous hemodialysis (CVVHD) were transitioned to CVVHDF. CVVHD was used in 3 encounters. The median 50% reduction time for ammonia was 8 h (range 3–15 h). The median duration of CRRT treatment was 40 h (range 24–89 h). Survival to hospital discharge occurred in 12 encounters (92.3%). Eleven encounters (84.6%) were treated with different vasoactive agents. In those encounters, the median vasoactive medications’ start time was the 6th hours (range 2–60 h) of CRRT. There was no association between the vasoactive index score and pre-dialysis ammonia concentration. Conclusions: CRRT achieves timely control of hypeammonemic states. Hemodynamic instability necessitating intervention with vasoactive medications is a common finding in patients with hyperammonemia.

To determine whether there were diffusion tensor imaging (DTI) changes in the brain among children with Type 1 diabetes mellitus (DM) and investigate the correlation between the fractional anisotropy (FA) and apparent diffusion coefficient (ADC) values and neurocognitive functions.35 children with Type 1 DM and 21 age-matched healthy control subjects were included. Neurocognitive functions of subjects with Type 1 DM were evaluated. In both groups, FA and ADC values were calculated in 20 different locations. The association between neurocognitive function tests and FA and ADC values was investigated.Subjects with diabetes had significant changes in FA and ADC values in widespread brain regions compared with the healthy control group. ADC values in the caudate nucleus were negatively associated with verbal point. Increased ADC values in the genu of the corpus callosum were positively associated with Stroop test. There was a negative correlation between the ADC values of the parietal white matter and the judgment of line orientation test. FA values of the inferior longitudinal fasciculus were positively correlated with performance point. However, a negative correlation was noted between FA values of mid-brain and intelligence quotient level as well as another negative correlation between FA values of the posterior crus of the internal capsule and thalamus with verbal point.Subjects with diabetes demonstrated significant changes in FA and ADC values in widespread brain regions, and such changes could be early features of injury to myelinated fibres or axonal degeneration. Our findings suggest that brain damage may have begun at the cellular level in the initial stage of Type 1 diabetes and neurocognitive impairments may be inevitable.DTI can demonstrate ADC and FA changes which are well correlated with neurocognitive dysfunction in the brains of children with Type 1 DM. This may help us in guiding preventive measures in early period of the disease before deterioration of neurocognitive functions.

WOS: 000419796200002, Objective: Hypernatraemia has serious complications such as brain injury, brain oedema and seizure. In this study, the incidence among children hospitalized hypernatremia, causes, development time, clinical features, and morbidity, and aimed to reveal the effect on mortality. Method: In this retrospective study, clinical and laboratory data from patients with hypernatremic were recorded. The study period was 33 months. The groups were separated into two groups; group I: Hypernatremia was present at hospital admission, group II: Hypernatremia was acquared after the hospitalization. Results: Overall incidence of hypernatraemia was 1.3% of all hospitalised children. While 42% of patients were from group I, 58% of patients had acquired hypernatremia during hospital stay. In group I, 61% of patients had infections on hospital admission. The most common cause of hypernatraemia in group II was neurological disorders (53%). The mortality rate was 30.5% (11/36) in patients with hypernatraemia on admission, 67.3% (33/49) in those with hospital-acquired hypernatraemia (P0.05. Conclusion: Hypernatraemia in pediatric age is associated with mortality and morbidity, and should be closely monitored in pediatric patients hospitalized for any reason in order to prevent complication.

Obesity is an important health issue, the prevalence of which is increasing in childhood. The aim of this study was to examine urinary renal injury markers in order to determine the renal effect of obesity and its comorbidities in a pediatric population.Eighty-four obese children and 64 healthy control subjects were enrolled in the study. We checked their urine using N-acetyl-beta-D-glucosaminidase (NAG), neutrophil gelatinase-associated lipocalin (NGAL), kidney injury molecule-1 (KIM-1), and microalbumin as renal injury markers. Associations of renal damage markers with hypertension, an impaired glucose tolerance test, and insulin resistance were assessed.Obese individuals had higher urinary NAG and KIM-1 values compared to those of healthy controls (p = 0.027, p = 0.026). There was no difference in urinary NGAL between obese and lean subjects (p = 0.885). Urinary renal injury markers were not statistically different in the obese group when checked for impaired glucose tolerance, insulin resistance, and hypertension (p 0.05).This study shows that urinary NAG and KIM-1 could be used as a screening method for detection of early renal damage in obese children.

Ob­jec­ti­ve: We aimed to determine the association of thyroid functions with the components of metabolic syndrome (MS) and non-alcoholic fatty liver disease (NAFLD) in pediatric obese patients. Methods: The study included 109 obese children (aged 9-15 years) and a control group of 44 healthy age and gender-matched children of normal weight. NAFLD was diagnosed by conventional ultrasound examination. We assessed the anthropometric data and serum biochemical parameters including lipid profile, alanine aminotransferase (ALT), fasting glucose and insulin levels and thyroid stimulating hormone (TSH), free thyroxine (fT4) and free triiodothyronine (fT3) levels. The homeostasis model assessment of insulin resistance (HOMA-IR) was calculated as a measure of IR. Results: The mean age and gender distributions in the groups were similar (p=0.23). The mean body mass index (BMI) z-scores of obese children with grade 2-3 NAFLD were significantly higher than those of the obese children without hepatic steatosis (p

Hatun, Sukru/0000-0003-1633-9570; Mengen, Eda/0000-0003-1597-8418; binay, cigdem/0000-0002-7749-8818; UCAKTURK, Seyit Ahmet/0000-0001-8666-4454 WOS: 000381646900004 PubMed: 27423071 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 3 months of data collection period between October 2012 and July 2013. Results: Mean age of patients was 11.3 +/- 3.8 years. Mean duration of DM was determined as 3.7 +/- 3.1 years. 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 9%(75 mmol/mol). Hypoglycemia was reported in 145 (29.1%) patients and the number of severe hypoglycemic attacks in the last 3 months 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. (C) 2016 Elsevier Ireland Ltd. All rights reserved. Sanofi Study was funded by Sanofi.

Background: This study was conducted to investigate CTNS (cystinosin, lysosomal cystine transporter) gene mutations and the clinical spectrum of nephropathic cystinosis among patients diagnosed with the disease in a single center in Turkey. Methods: Patients’ clinical and laboratory data were extracted from an electronic health registry. Molecular CTNS gene analysis was performed using either next-generation sequencing or Sanger sequencing. Results: Eleven patients (age range: 1.5–12 years) from nine families were identified. The presenting complaint was growth retardation in seven patients; polydipsia and polyuria in three patients; and vomiting in two patients. At presentation, electrolyte loss was noted in all patients, of which eight patients presented with metabolic acidosis, and three patients presented with metabolic alkalosis. All patients also presented with proteinuria and glucosuria, and four patients developed varying degrees of renal insufficiency, for which peritoneal dialysis was initiated in one patient. Cystine crystals were detected via ocular examination in one patient at presentation. No cystine crystals were detected among patients who underwent bone marrow aspiration. In the CTNS gene, a p.T7FX7 (c.18-21del4bp) mutation was detected in three patients, whereas a p.E227E (c.681 G>A) (homozygous) mutation was detected in eight patients. Conclusions: We detected two distinct mutations, p.T7FX7 (c.18-21del4bp) and p.E227E (c.681 G>A) (homozygous), in the CTNS gene in 11 patients with cystinosis from the East Anatolian region of Turkey. Patients with a homozygous c.681 G>A (p.E227E) mutation are more likely to develop chronic renal failure and should be monitored closely, whereas patients with a p.T7FX7 (c.18-21del4bp) mutation have a milder phenotype. Additionally, metabolic alkalosis does not exclude cystinosis, although cystinosis is a cause of proximal renal tubular acidosis.

WOS: 000382752700003, Objective: Vitamin D is essential for bone development and health, and deficiency resulting in rickets and skeletal deformities is seen mainly during rapid growth. Hereditary vitamin D dependent rickets type I and type II rickets is a very rare form of rickets, characterized by 1-alpha-hydroxylase deficiency or end-organ resistance to vitamin D. We aimed to investigate, clinical and laboratory characteristics of eight cases with Vitamin D-dependent rickets (VDRR). Method: The mean age of patients during diagnosis was 2.6 years. Excluding one patient, others were males (87.5%). Results: Mean laboratory values during referral was calcium 7.5 +/- 1,5 mg/dl, phosphorus 4 +/- 1.2 mg/dl, alkaline phosphatase (ALP) 1679 +/- 641 U/L and parathyroid hormone (PTH) 524 +/- 498 pg/ml. Patients received 1.2 mu g/kg/day calcitriol. During follow-ups serum ALP and PTH values of patients turned to normal levels. Conclusion: In rickets, cases with persistent increased serum ALP and PTH levels it will be appropriate to investigate serum 25 (OH) D levels in cases diagnosed with vitamin D-dependent rickets even though hypocalcaemia is absent. Administration of adequate doses of calcitriol in some cases is able to clinical and laboratory values return to normal.

Objective: The aim of this study was to estimate the prevalence of overweight and obesity in school children in Eastern Turkey. Methods: This study included 9048 school children aged 6-18 years. The subjects were classified as overweight and obese, according to the International Obesity Task Force. Results: We found prevalence of overweight of 11.1% in the studied population. It was detected that 2.2% of the population in the study was obese; 2.1% of males and 2.3% of females. While the prevalence of obesity was extremely low before 9 ages and after 15, it reached to high values at puberty and just before pubertal period in boys. The prevalence of overweight was higher in girls and reached to peak point at pubertal ages. Generally, the prevalence of obesity and overweight was slightly higher in girls than in boys, although the boys were more obese in prepubertal ages. Conclusion: Overweight and obesity are concerns for children and adolescents in low socio-economic status regions as well.

Summary Objective Nonsyndromic autosomal recessively inherited nongoitrous congenital hypothyroidism (CHNG) can be caused by mutations in TSHR, PAX8, TSHB and NKX2-5. We aimed to investigate mutational frequencies of these genes and genotype/phenotype correlations in consanguineous families with CHNG. Design Because consanguinity in individuals with a presumptive genetic condition is often an indicator of an autosomal recessive inheritance and allows firmer correlations to be established between genotype and phenotype, we planned to execute our study in consanguineous families. Patients Hundred and thirty-nine children with CHNG phenotype born to consanguineous families. Measurements First, we investigated cases for evidence of linkage to the four known CHNG genes by microsatellite marker analysis. Mutation analysis by direct sequencing was then performed in those cases in whom linkage to the relevant candidate gene could not be excluded. In addition, in silico analysis of the predicted structural effects of TSHR mutations was performed and related to the mutation-specific disease phenotype. Results Homozygous germline TSHR mutations were detected in six families (5%), but no mutations were detected in PAX8, TSHB and NKX2-5. Four of TSHR mutations had not previously been described. Genotype–phenotype correlations were established and found to be related to the predicted structural effects of the mutations. Conclusions Known causative genes account for the development of CHNG only in a minority of cases, and our cohort should provide a powerful resource to identify novel causative genes and to delineate the extent of locus heterogeneity in autosomal recessively inherited CHNG.

Celiac disease (CD) is a disease of the small intestine caused by an immune response to ingested gluten. Idiopathic thrombocytopenic purpura (ITP) is a common acquired bleeding disorder of childhood. It may follow a viral infection or immunization and is caused by an inappropriate response of the immune system. Autoimmune thyroiditis (AT) is a disease that occurs due to autoimmune mechanisms. Celiac disease associated with autoimmune thyroid disease is well known, but the association of CD, autoimmune thyroid disease, and ITP has been reported very rarely in the literature. In the current report, we have presented a case with CD, AT, and acute ITP, because this association is rarely seen, and to emphasize that CD and AT should be kept in mind in patients with ITP.

Objective: Insulin-like growth factor binding protein-4 (IGFBP-4), inhibits IGF actions under a variety of experimental conditions. Parathyroid hormone (PTH), 1.25-hydroxy(OH)vitamin D, IGF-I, IGF-II and transforming growth factor (TGF)-b are the major regulators of IGFBP-4 production in vitro. However, little is known about the in vivo regulation of circulating IGFBP-4 in humans. Methods: We measured serum concentrations of calcium (Ca), phosphorus (P), alkaline phosphatase (ALP), PTH, vitamin D, IGF-I, IGFBP-3, and IGFBP-4 in infants (n=22) with nutritional rickets before and after treatment of rickets with vitamin D (300 000 U single dose po). Results: The mean±SD age of the patients was 1.3±1.6 years (range 0.2-3). Serum Ca and P increased, whereas ALP and PTH decreased after treatment (Ca from 6.6±1.4 to 9.5±1.6 mg/dL, P from 3.9±1.4 to 5.4±0.8 mg/dL, ALP from 2590±2630 to 1072±776 IU/mL and PTH from 407±248 to 27.4±20.8 ng/dL, respectively). Vitamin D levels were low (7.8±2.5 ng/mL) and increased after treatment (18.1±4.0 ng/mL, p

Ellis-van Creveld syndrome (EVCS) or chondroectodermal dysplasia is a rare autosomal recessive disorder characterized by a variable spectrum of clinical findings. Classical EVC syndrome comprises a tetrad of clinical manifestations of chondrodystrophy, polydactyly, ectodermal dysplasia, and cardiac defects. The patient presented with short stature, polydactyly, triangular face and dental dismorphism was found appropriately as radiographic with ectodermal dysplasia. In addition to the presence of single atrium, mitral, tricuspid and pulmonary valve insufficiency and pulmonary hypertension wererevealed by echocardiography. Her history involved a sister who was dead in 3-month-ages

Bisphenol A (BPA) is known as an endocrine disruptor and it is supposed to have a role on the development of central precocious puberty (CPP). Kisspeptin, a hypothalamic peptide, is a neuromodulator of gonadotropin releasing hormone and it has an important role on regulation of the onset of puberty. The BPA levels in girls with CPP and premature thelarche (PT) and its relation with kisspeptin levels were investigated.Twenty-eight girls with CPP, 28 girls with PT and 22 prepubertal girls as a control group were enrolled to the study. Urinary BPA and serum kisspeptin levels were compared in the groups. Bivariate correlations were performed to evaluate the relations of BPA with kisspeptin and estradiol.There was no statistical difference between groups regarding BPA levels. Serum kisspeptin levels were higher in CPP group than controls [306.56 (interquartile range (IQR), 175.63–504.66) vs. 157.62 (IQR, 55.61–285.00) p: 0.008]. There were no correlations between BPA and kisspeptin levels (r: 0.088, p: 0.391) and between BPA and estradiol (r: –0.171, p: 0.144).The BPA levels did not differentiate between groups and it seems that the exposed amount of BPA in daily life did not affect kisspeptin levels in girls with CPP and PT.

The aim of the study was to determine the role of MnSOD Ala16Val and MPO G-463A gene polymorphisms in the pathogenesis of metabolic syndrome in obese children. A total of 97 obese children with insulin resistance and, as a control group, 96 healthy children were enrolled in the study. In the obese group, AA, AV and VV genotype frequencies of the MnSOD gene and GG, GA and AA genotype frequencies of the MPO gene were not significantly different from the frequencies found in the control group (p=0.555 and 0.530, respectively). In the obese group, children who carry both VV (for MnSOD) and GG (for MPO) alleles (n= 26) had higher HOMA-IR levels (6.51 ± 3.91 vs 5.03 ± 2.12) than those of all other genotype combinations (n=71) (p=0.013). Children who have the maximum risk of developing oxidative stress with the combination of the VV (for MnSOD) and GG (for MPO) genotypes had higher HOMA-IR levels, suggesting these polymorphisms may lead to insulin resistance.

To investigate relationship between anthropometric values of premature babies with their's glucose, insulin, leptin, and ghrelin at birth and on day 15.We analyzed fasting and postprandial glucose, insulin, leptin, and ghrelin levels at birth and on day 15 in babies born prematurely between 24 and 37 weeks, and who did not have serious problems aside from prematurity at birth.Fasting glucose, insulin, leptin and ghrelin values of babies at birth and on day 15 were significantly lower than postprandial values (all p values p 0.001). There were positive correlations between the mean insulin, leptin, and ghrelin levels with the gestational age, birth weight, body mass index, head circumference of babies at birth, and anthropometric values on day 15 (all r values 0.400, all p values 0.05). Fasting glucose, leptin, and ghrelin values of mothers birth were significantly lower than post-prandial values (all p values p 0.05).The positive correlations between the insulin, leptin, and ghrelin values of babies at birth with gestational age and anthropometric values suggest that both hormones play important roles in fetal and neonatal growth and development.

WOS: 000351307200006, PubMed ID: 25800474, 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.

WOS: 000347785700006, PubMed: 25541894, Objective: Growth charts are essential tools used to assess children's health status. The aim of the present study was to determine the effect of environmental factors on the growth of children of a common geographic background. We constructed growth charts for children living in the East of Turkey and compared them with those for Turkish children living in other regions or countries. Methods: Growth data were obtained from 6 917 school children living in Eastern Turkey. The median values on smoothed percentile curves for the study subjects were compared with those for Turkish children living in the West of Turkey, in Western Europe and in Germany. Results: Children living in Turkey were lighter than their European peers at early ages. Weight curves of children living in the West of Turkey reached those of their European peers, after 11 years of age in boys and after 12 years of age in girls. At all ages, girls and boys in our region had the lowest weight values. Between 7 and 11 years of age, the median height in boys and girls were similar in the West of Turkey and in Europe. At older ages, median height was higher in Turkey. Girls and boys living in Eastern Turkey were the shortest children until 16 years of age; after that age, their height was similar to their peers. Conclusions: Weight may interact with environmental factors, but genetic potential appears to be the most important factor determining height at 17 years of age. Growth patterns of children should be evaluated using specific reference values for specific regions.

Celiac crisis is a life threatening and very rare complication of Celiac disease. Clinically, it is characterized by severe diarrhea, dehydration and metabolic disturbances like hypokalemia, hypomagnesemia, hypocalcemia, hypoproteinemia. A 2.5-years-old-girl with diarrhea, weight loss, abdominal distention, extremities edema, vomit which occurred after the beginning of supplementary nutrition was presented to emphasize that celiac crisis should be keep in mind in patient with gastrointestinal symptoms, which are best known in celiac disease, metabolic disturbance and abdominal distention.

AIM Hypocalcaemia evaluation of the clinical, biochemical and radiologicalfeatures of 91 infants with rickets who presented as hypocalcaemic convulsions. SUBJECTS AND METHODS Ninety-one hypocalcaemic infants who were brought to hospital with convulsion and diag-nosed with rickets related to vitamin D deficiency according to their clinical, biochemical and radio-logicalfeatures were retrospectively reviewed. RESULTS Mean values of the laboratory data were as follows: calcium 5.55 +/- 0.79 mg/dL, phosphorus 4.77 +/- 1.66 mg/dL, alkaline phosphatase 1525.5 +/- 925.4 U/L and parathormone 256.8 +/- 158.3 pg/mL. Serum 25-OH vitamin D levels were below normal (< 20 ng/mL) in 37 infants. CONCLUSION Vitamin D deficiency should be considered in infants presenting with hypocalcaemia. To avoid complications such as convulsions, clinicians should give vitamin D supplementation to such infants.

Congenital hypothyroidism (CH) is the most common neonatal endocrine disorder and results in mental retardation if untreated. Eighty-five percent of CH cases are due to disruptions in thyroid organogenesis and are mostly sporadic, but about 2% of thyroid dysgenesis is familial, indicating the involvement of genetic factors in the aetiology of the disease. In this study, we aimed to investigate the Mendelian (single-gene) causes of non-syndromic and non-goitrous congenital hypothyroidism (CHNG) in consanguineous or multi-case families. Here we report the results of the second part (n=105) of our large cohort (n=244), representing the largest such cohort in the literature, and interpret the overall results of the whole cohort. Additionally, 50 sporadic cases with thyroid dysgenesis and 400 unaffected control subjects were included in the study. In familial cases, first, we performed potential linkage analysis of four known genes causing CHNG (TSHR, PAX8, TSHB, and NKX2-5) using microsatellite markers and then examined the presence of mutations in these genes by direct sequencing. In addition, in silico analyses of the predicted structural effects of TSHR mutations were performed and related to the mutation specific disease phenotype. We detected eight new TSHR mutations and a PAX8 mutation but no mutations in TSHB and NKX2-5. None of the biallelic TSHR mutations detected in familial cases were present in the cohort of 50 sporadic cases. Genotype/phenotype relationships were established between TSHR mutations and resulting clinical presentations. Here we conclude that TSHR mutations are the main detectable cause of autosomal recessively inherited thyroid dysgenesis. We also outline a new genetic testing strategy for the investigation of suspected autosomal recessive non-goitrous CH.

This report highlights a rare presentation of vitamin B12 deficiency (concurrent psychotic disorder, seizures and hypertension). A 16-year-old girl presented with nervousness that had been persisting for 2 weeks. She had stopped eating and there was decreased self-care and she could not walk and sleep. Two days prior to admission, generalized tonic–clonic convulsions were noted. On physical examination, vital signs were normal, except for hypertension (150/100 mm Hg). She did not respond to conversation; she could not answer the questions. Mood was depressive and hallucinations were noted. Laboratory analyses were normal, except for a low vitamin B12 level (−1). The patient was not given any treatment of hypertension, psychosis or seizures, except vitamin B12 injections. After that, she showed improvement within 1 week. In the 7 days of hospitalization, the arterial blood pressure returned to normal, psychotic symptoms were resolved, the visual hallucinations and the depressive mood subsided, and she could eat and speak clearly. No hypertension or convulsions have been detected on the control examinations, and she has now been followed-up without any symptoms or findings. In conclusion, with this report we emphasized that psychosis, seizures and hypertension can be a rare manifestation of vitamin B12 deficiency, which is reversible with therapy and serum vitamin B12 level should be checked in patients who do not have an obvious cause for psychosis, seizures or hypertension.

Wolfram syndrome, also named -DIDMOAD- (diabetes insipidus, diabetes mellitus, optic atrophy, and deafness), is an inherited association of juvenile-onset diabetes mellitus and optic atrophy as key diagnostic criteria. Renal tract abnormalities and neurodegenerative disorder may occur in the third and fourth decade. The wolframin gene, WFS1, associated with this syndrome, is located on chromosome 4p16.1. Many mutations have been described since the identification of WFS1 as the cause of Wolfram syndrome. We identified a new homozygous WFS1 mutation (c. 1532T>C; p.Leu511Pro) causing Wolfram syndrome in a large inbred Turkish family. The patients showed early onset of IDDM, diabetes insipidus, optic atrophy, sensorineural hearing impairment and very rapid progression to renal failure before age 12 in three females. Ectopic expression of the wolframin mutant in HEK cells results in greatly reduced levels of protein expression compared to wild-type wolframin, strongly supporting that this mutation is disease-causing. The mutation showed perfect segregation with disease in the family, characterized by early and severe clinical manifestations. (C) 2011 Elsevier Masson SAS. All rights reserved.

OBJECTIVE To determine the oxidative stress and trace element levels in vivo in patients with nutritional rachitism associated with vitamin D deficiency. MATERIALS AND METHOD A total of 30 patients, 18 males and 12 females, were included in the study. Age, sex, medical history, vital, and physical examination findings of each patient documented at presentation were recorded. Serum calcium, phosphorus, alkaline phosphatase, parathormone, and 25-OH vitamin D levels, as well as oxidant and antioxidant system parameters and trace element levels were studied. After being diagnosed with rachitism, the patients were administered a single dose of 300,000 IU vitamin D by intramuscular injection. The same analyses were repeated post-treatment. Thirty children with normal anthropometric measurements were included as the control group. The analyses described above were performed only once for the control group. RESULTS Serum calcium, phosphorus, alkaline phosphatase, parathormone, and 25-OH vitamin D levels were different between the controls and children in the patient group (p

WOS: 000209012700002, PubMed ID: 22766261, Objective: Normosmic idiopathic hypogonadotropic hypogonadism (nIHH) is characterized by failure of initiation or maintenance of puberty due to insufficient gonadotropin release, which is not associated with anosmia/hyposmia. The objective of this study was to determine the distribution of causative mutations in a hereditary form of nIHH. Methods: In this prospective collaborative study, 22 families with more than one affected individual (i.e. multiplex families) with nIHH were recruited and screened for genes known or suspected to be strong candidates for nIHH. Results: Mutations were identified in five genes (GNRHR, TACR3, TAC3, KISS1R, and KISS1) in 77% of families with autosomal recessively inherited nIHH. GNRHR and TACR3 mutations were the most common two causative mutations occurring with about equal frequency. Conclusions: Mutations in these five genes account for about three quarters of the causative mutations in nIHH families with more than one affected individual. This frequency is significantly greater than the previously reported rates in all inclusive (familial plus sporadic) cohorts. GNRHR and TACR3 should be the first two genes to be screened for diagnostic purposes. Identification of causative mutations in the remaining families will shed light on the regulation of puberty.

Cerebral venous sinus thrombosis (CVST) is an uncommon disease in childhood. In the largest study carried out so far, the incidence was 0.67 case per 100 000 children per year. A number of etiologies and risk factors have been so far identified for CVST in childhood, including head trauma, local and systemic infectious diseases, malignancies, and autoimmune diseases. Celiac disease (CD) is a disease of the small intestine caused by an immune response to ingested gluten. Epilepsy, bilateral occipital calcification, cerebellar ataxia, degenerative central nervous system disease, peripheric neuropathy, myopathy, and rarely stroke were defined as neurologic disorders. In this presentation, we report 2 cases (16-year-old boy and 2-year-old boy) with CD and CVST. We emphasized that CD can be investigated in patients with CVST even with the absence of gastrointestinal symptoms. Finally, we suggest that algorithm of CVST can be involved in the investigation of CD.

Mucopolysaccharidosis type VI (MPS VI), or Maroteaux-Lamy syndrome, is a lysosomal storage disorder that results from a deficiency of the enzyme N-acetylgalactosamine-4-sulfatase or arylsulfatase B (ASB). It is a relatively rare disorder, with an estimated incidence of 1 in 248,000 to 1 in 300,000. The diagnosis is made on the basis of findings of elevated urine glycosaminoglycans and a deficiency of ASB activity in leukocytes or cultured fibroblasts. In treatment of MPS VI, enzyme replacement therapy (galsulfase; human recombinant ASB enzyme) became available. Infusions of galsulfase were generally well tolerated. But in some patients, infusion-associated reactions including rash, urticaria, headache, hypotension, nausea, and vomiting were documented and were managed successfully by interrupting or slowing the rate of infusion and/or by the administration of antihistamines, antipyretics, corticosteroids, or oxygen. Here, we report a case with MPS VI who developed thrombocytopenia after third dose of therapy. To the best of our knowledge, this is the first report about thrombocytopenia associated with galsulfase therapy in the literature. Additionally, with this report, we want to share our approach for this case.

Aim To evaluate the clinical findings, risk factors, therapy and outcome in 946 children with nutritional rickets. Patients and methods This retrospective study included a review of medical records of patients with nutritional rickets between March 2004 and 2009. Patients who displayed both the biochemical inclusion criteria and the clinical signs/symptoms or radiological signs of rickets were included in the study. Results The present study included 946 patients aged between 4 months and 15 years. Distribution of the cases showed a density between December and May. The age at diagnosis, showed two peaks and most of the patients were in the age range 0-23 months and 12.0-15 years. In infants and young children, most of the patients had been admitted to the hospital due to infectious diseases. In older children, short stature and obesity were the most common complaints. Conclusion Children aged between 0-23 months and 12.0-15 years were under most risk for nutritional rickets, especially in winter and spring and vitamin D should be given to them as supplementation dose.

Aim: To investigate the ratio of rickets and vitamin D deficiency in healthy adolescents at Van region. Method : Totally 126 cases were included in this study. All cases were evaluated for the presence of rickets symptoms, daily sun exposure,and vitamin usage, covering and eating habit. Diagnosis of rickets was made based on biochemical findings. The children whose vitamin D levels were lower than 10 ng/dl were accepted as vitamin 25(OH)D3 deficiency, but whose levels between 10-20 ng/dl were accepted as vitamin D insufficiency. Result: Sixty girls (47.6%) and 66 boys (52.4%) were included in this study. They were between 9 and 17 years old (11.94 ± 1.9 years). Vitamin D levels in 60 (47.6%) cases were normal, but 48 (38.1%) cases had rickets, 13 (10.3%) cases had vitamin D insufficiency and 5 (4.0%) cases had vitamin D deficiency. There was no statistically significant difference in the incidence of rickets between the cases with or without covered-dress. However, there was a significant difference in the incidence of vitamin D insufficiency (p< 0.05). All of the cases had less daily calcium, phosphorus, protein and vitamin D intake than recommended daily amount. In the rickets group, alkaline phosphatase levels were significantly higher comparing with the others (p< 0.05), but there was no difference in plasma intact parathyroid hormone levels. Conclusion: Our findings revealed that most adolescents who appeared to be healthy (52.4%) could have vitamin D insufficiency. Therefore, we believe that dietary education and/or vitamin D prophylaxis might be given to all adolescents. However, more extensive researches should be done to elucidate of our suggestion′s correction

Celiac disease (CD) is manifested by a variety of clinical signs and symptoms that may begin either in childhood or adult life. Neurological symptoms without signs of malabsorption have been observed for a long time in CD. In this report, an 8-year-old girl with CD presented with rarely seen dilated cardiomyopathy and stroke. The girl was admitted with left side weakness. Her medical history indicated abdominal distention, chronic diarrhea, failure to thrive, and geophagia. On physical examination, short stature, pale skin and a grade 2 of 6 systolic murmur were detected. Muscle strength was 0/5 on the left side, and 5/5 on the right side. Coagulation examinations were normal. Tests for collagen tissue diseases were negative. Factor V Leiden and prothrombin GA20210 mutations were negative. Tandem mass spectrophotometry and blood carnitine profiles were normal. Brain magnetic resonance imaging and cerebral angiography showed an infarction area at the basal ganglia level. Examinations of serologic markers and intestinal biopsy revealed CD. We emphasize that in differential diagnosis of ischemic stroke, CD should be kept in mind. (C) 2010 Baishideng. All rights reserved.

Vitamin B12 and folate deficiency causing neuropsychiatric and thrombotic manifestations, such as peripheral neuropathy, subacute combined degeneration of cord, dementia, ataxia, optic atrophy, catatonia, psychosis, mood disturbances, myocardial infarction and portal vein thrombosis are well known. This present report highlights an unusual presentation of vitamin B12 deficiency-psychotic disorder, extrapyramidal symptoms in a 12-year-old boy. His symptoms responded to parenteral vitamin B12 therapy. So with this report we emphasized that serum vitamin B12 and folate levels should be measured, especially in those patients who present with other known neuropsychiatric features of vitamin B12 and folate deficiency.

Context: The Middle East has a high incidence of rickets, and it is also common in Europe-dwelling children of Middle Eastern origin. Objective: The objective of the study was to explore the mechanisms leading to rickets in children of the Middle East. Design and Setting: We conducted a prospective study in 98 rachitic and 50 controls (aged 6 months to 4 yr) from university and community outpatient hospitals in Egypt and Turkey. Main Outcome Measures: We collected epidemiological, maternal, nutritional, radiographic, and biochemical parameters; markers of bone turnover; and vitamin D receptor (VDR) gene polymorphisms. Results: Epidemiological factors had a key role in pursuit of rickets; Egyptian and Turkish patients had lower (P < 0.01) dietary calcium intake than controls and the recommended dietary intakes, and serum 25-hydroxyvitamin D levels were reduced in patients, the difference with controls being significant (P < 0.001) only in Turkey, although rickets was more severe in Egypt as determined by the x-ray score (P < 0.05). In Turkey, the F VDR allele frequency was significantly (P < 0.05) increased in patients. The BB VDR genotype was associated with lower serum 25-hydroxyvitamin D levels in both patients and controls and with severity of rickets. Conclusions: In Turkey most patients had vitamin D deficiency, whereas in Egypt they had mostly calcium insufficiency combined with vitamin D deficiency. In this environ, VDR genotypes may predispose to rickets by increased frequency of the F allele. The unique environs and genetic predisposition have to be accounted for in the design of preventive measures, rather than using European or American recommended dietary intake for calcium and vitamin D.

Alström syndrome (AS) is a rare autosomal recessive disorder, characterized by retinal degeneration, progressive hearing impairment, truncal obesity and non-insulin dependent diabetes mellitus. A 6-year-old girl was admitted with aphasia, deafness, strabismus, abdominal distention, and weakness on the right body side. The physical and laboratory examination revealed psychomotor retardation, right hemiparesis, sensorioneural hearing loss, aphasia, eye and teeth abnormalities, hyperpigmentation, truncal obesity, hepatosplenomegaly, severe iron deficiency anemia, delayed bone age, and cerebral hemiatrophy. Based on these abnormal findings she was diagnosed as AS. According to our knowledge this is the first case of AS with cerebral involvement. This last finding may be a component of the syndrome. Key words: Alström syndrome; brain involvement, case report