Search

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.

Background: 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., Methods: 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., Results: 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)., Conclusions: 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.

Objective: 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., Methods: 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., Results: 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., Conclusion: 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., Advances in Knowledge: 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.

Objective: Cardiovascular, respiratory and musculoskeletal system disorders which may affect the functional exercise capacity are common in obese patients. We aimed to investigate the functional exercise capacity and its relationship with functional pulmonary capacity in obese children., Methods: A total of 74 obese and 36 healthy children as a control group were enrolled in the study. Pulmonary functions and functional exercise capacity were measured by spirometry and six-minute walk test (6 MWT), respectively., Results: The distances covered during the 6 MWT in obese and control groups were 570.9 ± 67.5 and 607.8 ± 72.5 meters, respectively (p=0.010). In spirometric pulmonary function tests (PFTs), forced expiratory volume in 1 sec (FEV1) and forced mid-expiratory flows (25-75) were lower in the obese group (p=0.048 and p=0.047, respectively), whereas forced vital capacity (FVC), the FEV1/FVC ratio and peak expiratory flow were not statistically different between the obese and control groups. Multiple regression analysis revealed that among all parameters of anthropometric measures and PFTs, only body mass index standard deviation score (BMI-SDS) was the independent factor influencing 6 MWT., Conclusion: Functional exercise and lung capacities of obese children were diminished as compared to those of non-obese children. The most important factor influencing functional exercise capacity was BMI-SDS.

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.

Objective: To investigate relationship between anthropometric values of premature babies with their's glucose, insulin, leptin, and ghrelin at birth and on day 15., Methods: 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., Results: 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)., Conclusions: 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.

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

Objective: 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: 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., Methods: 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., Results: 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)., Conclusions: 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.

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<0.001). Median total cholesterol levels were similar in all the groups (p=0.263). Low-density lipoprotein cholesterol and triglyceride levels increased and high-density lipoprotein cholesterol levels decreased significantly as the grade of steatosis increased (p<0.001, p<0.05, and p=0.05, respectively). Median alanine aminotransaminase (ALT) and HOMA-IR levels of obese children with grade II-III NAFLD were significantly higher than those of obese children without NAFLD (p=0.01) and obese children with grade I NAFLD (p=0.001). CIMT was significantly correlated with the grade of steatosis (p<0.001) and level of ALT (p=0.005). Linear regression analysis showed that the grade of hepatosteatosis had a significant effect on CIMT. FMD decreased as the grade of hepatosteatosis increased, but it did not reach a significant level., Conclusion: The obese children with hepatosteatosis showed increased CIMT, as indicated by the grade of steatosis, compared with healthy controls and obese children without hepatosteatosis. FMD was not superior to CIMT in predicting the risk of early atherosclerosis.

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.

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.

Objective: Oxidative stress has been reported to be involved in the pathogenesis of metabolic disorders related with obesity. The aim of the study was to investigate the association of oxidative stress and paraoxonase activities with non-alcoholic fatty liver disease (NAFLD) as well as metabolic syndrome., Materials and Methods: A total of 109 obese children and adolescents and 44 healthy and lean control subjects were enrolled in the study. According to their ultrasonographic steatosis scores, they were classified into four groups as follows: healthy children; obese, non-NAFLD; obese, grade I-NAFLD; and obese, grade II-III NAFLD. The biochemical parameters and insulin resistance (HOMA-IR) were evaluated from fasting samples. The plasma total antioxidant status (TAS), total oxidant status (TOS), and serum paraoxonase activities were measured and then oxidative stress index (OSI) was calculated as the indicator of degree of oxidative stress., Results: As the steatosis increased, the alanine aminotransferase, C-reactive protein, HOMA-IR, total cholesterol, and LDL cholesterol increased, whereas HDL cholesterol decreased. The TAS measurements were higher in the obese NAFLD group compared with that of the healthy control group. The TOS and OSI measurements did not differ between the groups. Paraoxonase activities increased significantly as steatosis increased., Conclusions: Among the children in this study, no relationship could be demonstrated between obesity with/without steatosis and oxidant/antioxidant status.

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<0.001). Mean ALT, triglyceride (TG) and LDL cholesterol increased and HDL-cholesterol significantly decreased as the hepatic steatosis increased (p<0.05). HOMA-IR levels in obese subjects with grade 2-3 NAFLD were significantly higher than those in both obese children without NAFLD and grade 1 NADFL (p=0.05 and 0.001, respectively). In the obese subjects, TSH levels were increased significantly as the degree of steatosis increased (p=0.04) but fT3 and fT4 levels were not different. In correlation analysis, TSH was significantly correlated with ALT, BMI SDS and the degree of steatosis., Conclusions: Obese children demonstrate an increase in TSH levels as the degree of steatosis increased.

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.

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., (Copyright © 2011 Elsevier Masson SAS. All rights reserved.)

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.

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<0.001). Analysis of trace element levels demonstrated markedly lower pretreatment zinc levels for the patient group compared to the controls, with a statistically significant difference (p=0.001). Comparison of pretreatment oxidant and antioxidant system markers between the patient and control groups demonstrated higher values for vitamin C, β-carotene, reduced glutathione, and superoxide dismutase in the control group, whereas MDA was higher in the patient group., Conclusion: The present study demonstrated increased oxidative stress, reduced antioxidant defence system in patients with nutritional rachitism, with reduced oxidative stress and a pronounced improvement in the antioxidant system with vitamin D treatment.

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.

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.

The aim of this study was to determine the frequency of thyroid autoimmunity in second grade primary school students and to examine the relationship between iodine and Hashimoto thyroiditis (HT). This was a cohort study performed with 1000 students. Urinary iodine levels, antithyroid peroxidase (anti-TPO) and antithyroglobulin (anti-Tg) antibodies were determined in all children. Children with anti-TPO or anti-Tg antibody positivity or with goiter were summoned for detailed examinations. In total, 36 cases (3.6%) were diagnosed as HT. The goiter frequency was found in 17.5% of the whole cohort. Additionally, iodine deficiency was found in 64.2% of all children. The median urinary iodine excretion was determined as 132 microg/L (range 382 microg/L) in the HT group, whereas it was 73 microg/L (range 390 microg/L) in children with goiter but without HT and 81 microg/L (range 394 microg/L) in normal children. The urinary iodine level of HT cases was significantly higher than the other two groups (p < 0.001). HT was also determined in 2% of patients with low urinary iodine levels, in 6.2% of patients with normal urinary iodine levels, and in 7.5% of patients with high urinary iodine levels. Our data demonstrates the close relationship between excessive iodine levels and autoimmunity.

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.

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., (© 2010 Blackwell Publishing Ltd.)

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.

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.

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<0.001). Serum IGF-I and IGFBP-3 levels both increased after treatment (IGF-I: 13.5±12.2 vs. 23.7±14.2 ng/mL, p<0.001 and IGFBP-3: 1108±544 vs. 1652±424 ng/mL, p<0.001). However, serum IGFBP-4 levels did not change significantly after treatment (18.8±8.0 vs. 21.5±4.8 ng/mL). No correlation between PTH and IGF-I, IGFBP-3 or IGFBP-4 was detected. Significant correlations were observed between PTH and ALP (r=0.53, p<0.05), and between IGF-I and IGFBP-3 (r=0.46, p<0.05)., Conclusion: The results demonstrate that contrary to in vivo studies, circulating IGFBP-4 levels are not influenced by secondary hyperparathyroidism in vitamin D deficiency rickets since IGFBP-4 levels did not change after normalization of PTH with vitamin D treatment.

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.

Symptomatic hypoglycemia is an unusual complication in children receiving oral purine analogues for treatment of childhood acute lymphoblastic leukemia (ALL). The exact mechanism of the hypoglycemic effect of the antimetabolic therapy remains unclear. Reduced hepatic glycogen stores or impaired hepatic glyconeogenesis may partly explain the hypoglycemia. To prevent hypoglycemia, food containing complex carbohydrates is recommended before sleep. In severe cases of hypoglycemia due to 6-mercaptopurine (6-MP), the dose can be given in the morning and if this fails 6-MP can be discontinued for a short period of time. We report a 3-year-old child who developed severe early morning hypoglycemia episodes that resolved after decreasing 6-MP while receiving non-high risk ALL therapy.

A previously healthy 30-day-old girl presented with seizures, irritability and inability to sleep for three days. Vitamin K was not given just after birth. She was lethargic. A multifocal clonic seizure was evident during examination. Anisocoria was diagnosed on eye examination. Brain magnetic resonance imaging showed intracerebral hemorrhage, ventricular dilatation, and hematoma in the left temporofrontal region extending to the hypothalamus. Central diabetes insipidus was diagnosed by water deprivation due to dehydration and hypernatremia, and then desmopressin was added to phenobarbital. The possible mechanism of central diabetes insipidus in our patient is damage of vasopressin pathway resulting from compression of hemorrhage. An operation of ventriculoperitoneal shunt was also performed due to hydrocephalus. While she was symptom-free except for neurological sequel during routine control examinations after discharging from hospital, the parents said that she died, most probably from bronchopneumonia, at the age of 7.5 months. In conclusion, we emphasize that prophylactic vitamin K should be administrated to all babies just after birth, and infants with intracranial hemorrhage should carefully be monitored for central diabetes insipidus.

A 12-year-old boy was admitted with electrical burn and loss of consciousness. On physical examination his general condition was poor. Extensive burn areas, second and third degree, were present on his face, scalp, bilateral auricles, right cervical region, shoulders, right axilla, upper region of the thorax, and proximal region of the upper extremities. The total burned surface area was about 25%. Pupils were isocoric, but response to light was bilateral poor. He was stuporous and responsive only to pain. Deep tendon reflexes were exaggerated and plantar responses were bilateral extensor. Bilateral decorticate rigidity was noted. Computerized tomography of brain revealed brain edema and right thalamic hemorrhage. Magnetic resonance imaging of brain, examined 25 days after admission, revealed right thalamic hemorrhage and mild right subdural effusion. He was discharged form hospital 40 days after admission. However, spastic quadriplegia and severe mental retardation remained as sequela. On the 4th month of follow-up, no improvement was noted in his neurological examination. On the 9th month of follow-up, his clinical condition was better, but bilateral electric cataract was diagnosed. Both eyes were operated on and intraocular lenses were implanted with good results. Now he is 16th month of follow-up: neurological examination revealed only mild hemiparesis on the left side and mild articulation disorder. His school performance was moderate and intelligence quotient was 71. Magnetic resonance imaging of brain showed markedly improvement of the hemorrhage. To our best knowledge thalamic hemorrhage resulting from high-voltage electrical injury has not previously been reported in the literature.

Deadly nightshade (Atropa belladonna) intoxication has been infrequently reported in both children and adults in the literature. In this article, the clinical and laboratory findings of 49 children with acute deadly nightshade intoxication are reviewed. Our purpose was to enlighten the findings of deadly nightshade intoxication in childhood. The most common observed symptoms and signs were meaningless speech, tachycardia, mydriasis, and flushing. None of the children required mechanical ventilation or died in our series. The patients were categorized into two groups, mild/moderate and severe intoxication. Children with and without encephalopathy were accepted as severe and mild/moderate intoxication, respectively. While 43 children were placed in the group of mild/moderate intoxication, six were in severe intoxication group. We found that meaningless speech, lethargy, and coma were more common, but tachycardia was less common in the severe intoxication group (children with encephalopathy) (P < 0.05). In the treatment, neostigmine was used in all children because of no available physostigmine in our country. In conclusion, our findings showed that the initial signs and symptoms of acute deadly nightshade intoxication might be severe in some children, but no permanent sequel and death were seen in children. We also showed that meaningless speech, lethargy, coma, and absence of tachycardia were ominous signs in deadly nightshade intoxication in childhood. Lastly, we suggest that neostigmine may be used in cases of deadly nightshade intoxication if physostigmine cannot be available.

Severe anemia, growth retardation, diabetes mellitus, cardiac disorders, and, infrequently, stroke are well-known complications of thalassemia major. We report a girl, age 7 years, 2 months, with beta-thalassemia major associated with chronic renal failure, diabetes mellitus, and cardiomyopathy in whom a silent stroke was noted during follow-up. She was diagnosed with thalassemia major at age 6 months, chronic renal failure at age 3 years, 3 months, and diabetes mellitus and cardiomyopathy at age 7 years. Although cranial computed tomography was found to be normal at the age of 3 years, 3 months, magnetic resonance imaging showed cerebral infarct in the right frontal region at 7 years, 2 months. A thrombophilic panel revealed increased factor VIII and decreased protein C concentrations. She died from disseminated intravascular coagulation at age 7 years, 9 months. We did not record any clinical findings of stroke during her follow-up. We think that diabetes mellitus, dilated cardiomyopathy, and increased factor VIII and decreased protein C concentrations led to the occurrence of cerebral infarct. In conclusion, we emphasize that children with thalassemia major should be monitored closely for stroke. We also suggest that stroke can show a silent progression in severely affected children, as in our case.

We studied serum calcium, phosphorus, alkaline phosphatase (ALP), thyroid hormones (total thyroxine [TT4], free thyroxine [FT4], thyroid-stimulating hormone [TSH]), parathyroid hormone (PH), and osteocalcine levels in children with epilepsy who had been receiving long-term carbamazepine (CBZ) therapy to determine whether there was any effect of CBZ therapy on these hormones. The study included 18 patients with epilepsy receiving CBZ and 16 healthy age-matched controls. The age ranged from 4-18 years (11.26 +/- 3.59 years) and 4.5-17 years (11.16 +/- 3.13 years) in the study and control group, respectively. The duration of CBZ use was between 10 months-5 years (3.12 +/- 1.09 years). When comparing the results we did not find any significant difference in serum calcium, phosphorus, ALP, osteocalcine and TSH and PH levels between the groups (p >.05). However, serum TT4 and FT4 levels were found to be significantly lower in the study group than those of control group (p <.05). However, we observed no clinical signs of hypothyroidism in all subjects. To these findings we suggest that serum thyroid hormone levels should be monitored in children receiving long-term CBZ therapy.

Background: Protein-energy malnutrition (PEM) results from food insufficiency as well as from poor social and economic conditions. Development of PEM is due to insufficient nutrition. Children with PEM lose their resistance to infections because of a disordered immune system. It has been reported that the changes occurring in mediators referred to as cytokines in the immune system may be indicators of the disorders associated with PEM., Aims: To determine the concentrations of pro-inflammatory cytokines in children with PEM, and to find out whether there was an association with the clinical presentation of PEM., Methods: The levels of serum total protein, albumin, tumour necrosis factor-alpha, and interleukin-6 were measured in 25 patients with PEM and in 18 healthy children as a control group. PEM was divided into two groups as kwashiorkor and marasmus. The kwashiorkor group consisted of 15 children and the marasmus group consisted of 10 children., Results: Levels of serum total protein and albumin of the kwashiorkor group were significantly lower than both the marasmus group and controls (p < 0.05). In view of tumour necrosis factor-alpha levels, there was no difference between groups (p > 0.05). While levels of interleukin-6 in both the marasmus group and the kwashiorkor group were significantly higher compared with controls (p < 0.05), there was no significant difference between the groups of marasmus and kwashiorkor (p > 0.05)., Conclusions: It was observed that the inflammatory response had increased in children with malnutrition.

In this study, we studied serum calcium, phosphorus, alkaline phosphatase, thyroid hormones (total thyroxine, free thyroxine, thyroid-stimulating hormone), parathyroid hormone, and osteocalcine levels in children with epilepsy who had been receiving long-term valproate (VPA) therapy in order to determine whether there was any effect of VPA therapy on these hormones. The study included 31 patients with epilepsy receiving VPA and 22 healthy age-matched controls. The age ranged from 15 months to 16 years and 18 months to 17 years in the study and control group, respectively. The duration of VPA use was between 12 months and 5 years (1.93 +/- 1.90 years). When comparing the results, we did not find any significant difference in any of the parameters, including serum calcium, phosphorus, alkaline phosphatase, osteocalcine, and thyroid and parathyroid hormone levels, between the study and control group. We suggest that VPA can safely be used with regard to thyroid and parathyroid dysfunction in childhood epilepsy.

Allgrove syndrome (triple-A syndrome) is an autosomal recessive disorder characterized by adrenocorticotropin hormone-resistant adrenal insufficiency, achalasia and alacrima. Aside from the classic features of the syndrome, several abnormalities including mainly neurological abnormalities have been reported in the syndrome. Herein, we presented a case of Allgrove syndrome associated with left renal ectopla. To the best of our knowledge renal abnormality in Allgrove syndrome has not been reported in the literature until now. We think that ectopic kidney diagnosed in our patient is coincidental because the incidence of renal ectopia is high, approximately 1 in 900 in population.

Melkersson-Rosenthal syndrome (MRS) is characterized by the triad of recurrent facial palsy, lingua plicata, and facial edema. Herein, we report a case of MRS associated with Ehlers-Danlos syndrome due to rare presentation. To the best of our knowledge only one case of MRS associated with Ehlers-Danlos syndrome has been reported in the literature until now.

Background: The Greulich-Pyle (GP) Atlas of skeletal maturation has been prepared in white children who born between 1917 and 1942 in the USA, and is frequently used for assessment of skeletal maturity. In this study, we investigated whether or not the GP method is sufficient for Turkish children for the determination of the skeletal age., Methods: Plain radiographies of left hands and wrists of 225 healthy boys between 7 and 17 years of age were taken. Pubic hair (PH) stages of boys were determined by using the Tanner criteria. Mean chronological ages and mean skeletal ages according to GP Atlas were compared for each age groups and each PH stage., Results: Mean skeletal ages were delayed 0.61, 0.72, 0.54, 0.39, 0.25, 0.39, and 0.32 years than the mean chronological ages in the 7-13 years age groups, respectively, and advanced 0.13, 0.01, 0.89, and 0.52 years in the 14-17 years age groups. In PH stages 1, 2, and 3, mean skeletal ages were delayed 0.67, 0.51 and 0.40 years than the mean chronological ages, respectively. In PH stages 4 and 5, mean skeletal ages were advanced 0.66 and 0.76 years than mean chronological ages., Conclusion: The results suggest that Turkish boys may have a different tempo of skeletal maturation during pubertal development from that of American children which GP standards were derived. Therefore, GP Atlas is not completely applicable to Turkish boys but can be used with some modification.

Infantile cortical hyperosteosis (ICH) is usually a self-limited disease of infancy with bony changes, soft tissue swelling, fever, irritability, decreased appetite, and decreased movement of the affected bones. Its description in isolated patients or in multiple members of families suggests the existence of two different forms, namely a sporadic form and a familial form with incomplete penetrance. In this article, we report a 2.5-month-old girl with ICH of sporadic form, due to unusual presentation.

A 3 year and 6 month old girl with epilepsy associated with dural arteriovenous malformation (DAVM), diagnosed on the MRI, is presented to emphasise the importance of DAVM in the aetiology of childhood epilepsy.

Anthrax, caused by the spore-forming bacterium Bacillus anthracis, is rarely seen in industrial nations but is common in developing countries. Cutaneous anthrax (CA), the most common form of the disease, accounts for 95% of cases and usually develops on exposed sites. This study reviews the clinical and laboratory findings of 21 patients diagnosed with CA during 2 separate epidemics in the Van region of Turkey. All patients had a history of direct contact with infected cattle. The patients, aged 1.5 to 64 years, included 13 females and 8 males. Of the patients, 9 were 15 years or younger. Skin lesions were localized on the hands and fingers in 15 patients, on the face in 3 patients, on the face and finger in 1 patient, on the chest and finger in 1 patient, and on the eyelid in 1 patient. Gram-positive bacillus were noted on Gram stains of material obtained from skin lesions in 2 patients. All but one patient was successfully treated with penicillin; the unresponsive patient was treated with cefuroxime and required plastic reconstructive surgery because of a skin defect on the eyelid.