Anthropometric findings from birth to adulthood and their relation with karyotpye distribution in Turkish girls with Turner syndrome.

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

Association of wider neck circumference and asthma in obese children.

BACKGROUND: Obesity is a well-established risk factor for asthma. Previous studies have reported that central obesity is associated with asthma. OBJECTIVE: To investigate the association between fat distribution, which is determined by anthropometric measures, including neck circumference (NC), and asthma in school-aged children. METHODS: Children diagnosed as having asthma were enrolled along with controls who were admitted to our outpatient department with allergic symptoms, such as rhinitis, urticaria and atopic dermatitis. Anthropometric measures, including height, weight, NC, waist circumference, and hip circumference, were obtained. Skin prick tests, blood eosinophil counts, and serum total IgE level measurements were performed. RESULTS: A total of 196 children (92 male [46.9%]) were included. Asthma was present in 102 patients (52.1%). Ninety-one of the patients (46.4%) were overweight, and 45 patients (22.9%) were obese. The NC of children with asthma was significantly higher than that of children in the control group. Grades defined according to NC percentiles were also significantly different between groups. In children with asthma, the prevalence of children with an NC higher than the 90th percentile (grade 6) was more frequent when compared with controls. The median NC of obese-overweight children with asthma was significantly higher compared with obese-overweight controls without asthma. Results of multivariable logistic regression analysis revealed that the presence of an NC in the greater than 90th percentile was associated with asthma in obese-overweight children. CONCLUSION: This study found that NC, which is a simple anthropometric measure, is associated with asthma in obese children.

Association of nerve conduction impairment and insulin resistance in children with obesity.

AIM: The objective of our study was to investigate nerve conduction in normoglycemic obese children. METHODS: A total of 60 children with obesity (30 female and 30 male) and 30 healthy children (15 female and 15 male) were enrolled in the study. Insulin resistance (IR) and other metabolic disturbances were investigated and nerve conduction was measured in all participants. Obese children were divided into groups according to the presence of IR. All results were compared between these subgroups. RESULTS: The nerve conduction velocity (NCV) of motor median nerves in the IR+ group was significantly higher than that in the IR- group and lower than that in the control group. The NCV of the motor peroneal nerve in the IR+ group was significantly lower than that in the IR- group. The sensory nerve action potential (SNAP) of the sensory median nerve was significantly lower in the IR+ group compared to that in the IR- group. The sensory sural nerve's SNAP was significantly lower in the IR+ group than that in the control group. CONCLUSION: Nerve conduction tests may help to detect early pathologies in peripheral nerves and to decrease morbidities in obese children.

Wider neck circumference is related to severe asthma in children.

BACKGROUND: Obesity is an established risk factor for asthma in children. Measures of central obesity are reported to be more associated with the severity of asthma in adults. The aim of the study was to investigate the association between fat distribution, which is determined by anthropometric measures including neck circumference (NC) and asthma severity in children. METHODS: Children with asthma who were followed in our pediatric allergy unit were consecutively recruited. Asthma severity was graded according to GINA guidelines. Children whose asthma was controlled with Step 1 or 2 treatment options formed Group 1 (mild asthma), whereas children who needed Step 3, 4, or 5 treatment options formed Group 2 (moderate-to-severe asthma). Anthropometric measures including height, weight, NC, waist circumference, and hip circumference were obtained. RESULTS: A total of 127 children (82 male, 64.6%) with a median age of 8.3 (6.4-11.3) years were included. Atopy was present in 77 (60.6%) patients. 91 patients (71.6) were in the mild asthma group. NC of children with severe asthma was significantly wider than children with mild asthma (29.0 cm (27.0-32.0) vs. 28.0 (26.0-30.0), p = 0.019). The prevalence of children with NC higher than 90th percentile was also more frequent in children with severe asthma (15 [41.7%] vs. 21 [23.1%]). Result of multivariable logistic regression analysis revealed that presence of NC >90th percentile was associated with severe asthma in children (odds ratio; [95% confidence interval] (2.52 [1.05-6.01]; p = 0.038). CONCLUSIONS: Neck circumference, which is a simple anthropometric tool, is associated with asthma severity in children.

Measures of ventricles and evans' index: from neonate to adolescent.

Ventricle sizes are important for the early diagnosis of hydrocephalus or for follow-up after ventriculostomy. Diameters of ventricles may change, especially in childhood. This study aims to provide normative data about ventricle diameters. Among 14,854 cranial MRI performed between 2011 and 2013, 2,755 images of Turkish children aged 0-18 years were obtained. After exclusions, 517 images were left. Four radiologists were trained by a pediatric radiologist. Twenty images were assessed by all radiologists for a pilot study to see that there was no interobserver variation. There were 10-22 children in each age group. The maximum width of the third ventricle was 5.54 ± 1.29 mm in males in age group 1 and 4.98 ± 1.08 mm in females in age group 2. The Evans' index was <0.3 and consistent with the literature. The third ventricle/basilar artery width ratio was found to be >1 and <2 in all age groups and both gender groups. Our study showed the ventricle size data of children in various age groups from newborn to adolescent. The ventricle volume/cerebral parenchyma ratio seems to decrease with age. We think that these data can be applied in clinical practice, especially for the early diagnosis of hydrocephalus.

Brachydactyly mental retardation syndrome in differential diagnosis of pseudopseudohypoparathyroidism.

Patients with Albright hereditary osteodystrophy (AHO) phenotype are usually seen in pediatric endocrinology policlinics when they are evaluated for short stature and/or obesity. Brachydactyly mental retardation syndrome (BDMR, OMIM #600430) is a rare genetic disorder caused by aberrations of chromosomal region 2q37 and characterized with AHO-like phenotype without any hormone resistance. Diagnosis of BDMR is based on the detection of the deletion on the long arm of chromosome 2. Diagnosis can usually be made with karyotype analysis but sometimes chromosomal deletion can only be detected by fluorescent in situ hybridization (FISH) screening. We report a patient with the AHO phenotype whose karyotype was normal but who was diagnosed with BDMR with FISH analysis showing 2q deletion. In pediatric endocrinology practice, in patients with AHO phenotype but without parathormone (PTH) resistance, BDMR should be considered. For the diagnosis of BDMR, the subtelomeric region of chromosome 2 should be screened for deletion by FISH analysis even in patients with normal karyotypes.

Oxidized low-density lipoprotein levels and carotid intima-media thickness as markers of early atherosclerosis in prepubertal obese children.

OBJECTIVES: Children with obesity have a high cardiovascular risk and an impaired oxidant-antioxidant status, which may lead to endothelial dysfunction and increased carotid intima media thickness (IMT) even in childhood. The aim of this study was to investigate the circulating oxidized low-density lipoprotein (LDL) concentrations and the IMT of carotid arteries in prepubertal obese children, and also to search for its possible association with carotid atherosclerosis. METHODS: Twenty-seven prepubertal obese children (age, 7.48±2.05 years; boys, 59%) and 30 healthy children (age, 7.80±2.19 years; boys, 55%) were included in the study. Serum concentrations of oxidized LDL, total cholesterol, triglyceride, high-density lipoprotein, LDL, and glucose were measured, and carotid IMT was determined by ultrasound. RESULTS: Serum oxidized LDL levels were significantly higher in prepubertal obese children than in healthy children (p<0.01). No significant correlation was observed between oxidized LDL levels and carotid IMT measurements. However, a significant positive correlation was found between oxidized LDL levels and body mass index, total cholesterol, and LDL-cholesterol. CONCLUSION: Our findings revealed that the oxidation of LDL starts early in obese children but the carotid IMT is not significantly affected. Also, oxidized LDL levels are more strongly associated with obesity and dyslipidemia than the carotid IMT in prepubertal children.

Penile anthropometry of normal prepubertal boys in Turkey.

AIM: The age-related values of penile length must be known to determine abnormal penis sizes and to follow the treatment of underlying diseases. The aim of this study is to evaluate abnormal penile length in Turkish children by establishing novel reference values for Turkish population and to compare the mean penile length and other parameters with alternates from different ethnic populations and geography. METHODS: This cross-sectional study was conducted on a voluntary basis between November 2008 and November 2009 from four centres in Turkey and comprised of 1278 healthy volunteered prepubertal children. Complete stretched penile length and penis circumference measurements were used for penile length and penis circumference evaluations, respectively. All measurements were taken twice by only one investigator, and mean values were recorded. RESULTS: Penile length and penis circumference for every age group were obtained, percentile curves were established and these findings were compared with the results of previous studies. Significant differences were found between penile length of Turkish children and recently used reference values. CONCLUSION: With this study, novel reference values for penile length in prepubertal children were presented to the literature.

The effects of oxcarbazepine and valproate therapies on growth in children with epilepsy.

AIM: This study aimed to evaluate the effects of monotherapy with valproate or oxcarbazepine on the linear growth of children with idiopathic epilepsy. METHODS: Antiepileptic treatment with valproate or oxcarbazepine was initiated in 76 patients. These were evaluated at baseline and at 6 and 18 months after commencement of therapy to determine height standard deviations (height z-scores). Serum ghrelin, insulin-like growth factor-1, and insulin-like growth factor-binding protein-3 levels were measured. RESULTS: In prepubertal patients receiving oxcarbazepine, height z-scores were elevated after 6 and 18 months of therapy (p = 0.008 and p = 0.001, respectively); in pubertal patients, a significant increase was noted at the 18th month of therapy (p = 0.004). In prepubertal patients receiving oxcarbazepine, serum standardized insulin-like growth factor-1 and insulin-like growth factor-binding protein-3 levels were significantly higher at the 18th month of therapy compared with baseline (p = 0.005 and p = 0.004, respectively). In puber-tal patients receiving valproate, serum ghrelin levels were significantly decreased at the 18th month of therapy compared with baseline (p = 0.006). CONCLUSION: Exposure to oxcarbazepine stimulated linear growth in epileptic patients through mechanisms involving the release of insulin-like growth factor-1 and insulin-like growth factor-binding protein-3. In contrast, expo-sure to valproate did not affect linear growth, but did lead to a decrease in serum ghrelin levels.

Molecular Diagnosis of Monogenic Diabetes and Their Clinical/Laboratory Features in Turkish Children

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

Importance of plasma N-terminal pro B-type natriuretic peptide, epicardial adipose tissue, and carotid intima-media thicknesses in asymptomatic obese children.

This study aimed to analyze the variations of N-terminal pro B-type natriuretic peptide, epicardial adipose tissue thickness, and carotid intima-media thickness in childhood obesity. The study participants consisted of 50 obese children in the study group and 20 nonobese children referred for evaluation of murmurs who proved to have an innocent murmur and were used as control subjects. All the subjects underwent transthoracic echocardiographic examination for determination of left ventricular systolic function and mass index, myocardial tissue rates, and myocardial performance index. Epicardial adipose tissue thickness and carotid intima-media thickness also were measured during echocardiography. Serum N-terminal pro B-type natriuretic peptide levels were measured at the time of evaluation. The left ventricle mass index was 40.21 + or - 10.42 g/m(2) in the obese group and 34.44 + or - 4.51 g/m(2) in the control group (p > 0.05). The serum N-terminal pro B-type natriuretic peptide level was 109.25 + or - 48.53 pg/ml in the study group and 51.96 + or - 22.36 pg/ml and in the control group (p = 0.001). The epicardial adipose tissue thickness was 5.57 + or - 1.45 mm in the study group and 2.98 + or - 0.41 mm in the control group (p = 0.001), and the respective carotid intima-media thicknesses were 0.079 + or - 0.019 cm and 0.049 + or - 0.012 cm (p = 0.001). The left ventricular systolic and diastolic functions showed no statistically significant correlations with N-terminal pro B-type natriuretic peptide levels, carotid intima-media thickness, or epicardial adipose tissue thickness values. The results show that measurement of serum N-terminal pro B-type natriuretic peptide level, carotid intima-media thickness, and epicardial adipose tissue thickness in asymptomatic obese children is not needed.

Plant growth regulator (4-chlorophenoxy acetic acid) increases apoptosis in gonads of rats without changing hormonal levels.

BACKGROUND/AIMS: Plant growth regulators are considered to leave minimal amounts of remnants and therefore cause no significant side effects in humans. In this study, we aimed to investigate the hormonal and histopathological effects of 4-chlorophenoxy acetic acid (4-CPA), a commonly used plant growth regulator, on the gonadal functions of rats. METHODS: The study was implemented on 64 Wistar albino rats (20 days old). Forty-eight rats received 4-CPA every day until 50 days of age. The rats were randomized into 4 groups (a control group and three 4-CPA groups with doses of 25, 50 and 100 mg/kg/day); each group was further divided into males and females, making a total of 8 groups. The levels of FSH, LH, testosterone, estradiol, leptin, inhibin-B and neuropeptide-Y were measured. Histopathological examination of the testes and ductus deferens in male rats, and ovaries and uterus of female rats (caspase-3 and -9 immunoreactivity) was performed. RESULTS: Although hormone levels were similar between the groups, rats that received 4-CPA showed significantly higher degrees of apoptosis compared to the control group (p < 0.001) and increased doses of 4-CPA were directly correlated with the amount of apoptosis (p < 0.001). CONCLUSION: 4-CPA induced apoptosis in the gonads of rats without concurrent changes in plasma hormone levels.

Prevalence of celiac disease in Turkish children with autoimmune thyroiditis.

The close association between celiac disease (CD) and autoimmune disorders is well documented in adult and pediatric patients. The aim of this study is to determine the prevalence of CD in Turkish children with autoimmune thyroiditis (AT). Sera from 101 children with AT (11 boys and 90 girls, from 2 to 18 years of age; mean age 12.28 +/- 3.26 years) and 103 healthy children (46 boys and 57 girls, from 3.5 to 17 years of age; mean age 12.18 +/- 3.11 years) were screened for CD using the IgA anti-tissue transglutaminase (IgA anti-tTG) antibody and total serum IgA. Small intestinal biopsy was offered to all antibody-positive patients. IgA anti-tTG was positive in eight children (7.9%) with AT. None of the serum samples of healthy children were positive for IgA anti-tTG antibody. Selective IgA deficiency was not detected in patients or controls. Intestinal biopsy was accepted by seven patients. In five patients (4.9%), subtotal villous atrophy was found. These findings indicate that the prevalence of CD is higher in Turkish children with AT than in healthy controls. Routine screening for CD should be performed in children with AT.

Genetic polymorphisms of FSHR, CYP17, CYP1A1, CAPN10, INSR, SERPINE1 genes in adolescent girls with polycystic ovary syndrome.

BACKGROUND: Polycystic ovary syndrome (PCOS), whose genetic basis is not completely well understood, is the most common endocrine disorder in women and it typically develops during adolescence. The aim of this study is to investigate the possible association between single nucleotide polymorphisms (SNPs) of FSHR, CYP17, CYP1A1, CAPN10, INSR, SERPINE1 genes and PCOS in adolescent girls. METHODS: DNA samples from forty-four adolescent girls with PCOS and 50 healthy controls were analyzed by PCR-RFLP and direct DNA sequencing to determine the genotypic frequency of 17 different polymorphic loci on the FSHR (A307T, N680S), CYP17 (-34 T/C), CYP1A1 (T6235C), CAPN10 (44, 43, 19, 63), INSR (exon 17 C/T), SERPINE1 (4G/5G) genes. Genotyping of exon 12 (six polymorphisms) and intron 12 (one polymorphism) of INSR gene by direct DNA sequencing was performed for the first time in this study. RESULTS: No significant differences were observed in the genotype and allele distributions of above mentioned polymorphisms between cases and control groups. CONCLUSION: Our data does not support an association between SNPs of FSHR, CYP17, CYP1A1, CAPN10, INSR, SERPINE1 genes and susceptibility to PCOS or related traits in Turkish adolescent girls.

A novel mutation in the SLC19A2 gene in a Turkish female with thiamine-responsive megaloblastic anemia syndrome.

Reported here is a 2-year-old girl who was diagnosed to have thiamine-responsive megaloblastic anemia during evaluations for her bilateral neurosensorial deafness. Besides reporting a new mutation on the gene SLC19A2 for the first time in the literature, we highlight the recognition of this syndrome--when megaloblastic anemia and diabetes mellitus coexists--and the role of thiamine replacement for the treatment of both disorders.

Localized abdominal Castleman disease masquerading as malabsorption syndrome.

Castleman disease is a rare lymphoproliferative disorder of unclear etiology. It usually presents as localized enlarged lymph nodes in children. Surgical excision is curative in localized form. Clinical findings of malabsorption are rarely reported in the literature. Herein, we describe a 14-year-old girl who presented with anemia, failure to thrive, osteoporosis, zinc, and vitamin deficiency. She was diagnosed as localized mesenteric mixed type of Castleman disease. Her clinical findings improved after surgical excision of the mass.

CTLA4 gene polymorphisms in children and adolescents with autoimmune thyroid diseases.

Two common forms of autoimmune thyroid diseases are Graves' disease and Hashimoto's thyroiditis. Cytotoxic T lymphocyte antigen 4 (CTLA4) encoded by the CTLA4 gene on chromosome 2q33 plays a role in susceptibility to Graves' disease and is probably important also for Hashimoto's thyroiditis as well as for the other endocrine autoimmune disorders. The CTLA4 locus is the only nonhuman leukocyte antigen locus that has been found in association with Graves' disease repeatedly. Particularly, association of three polymorphic markers of CTLA4 gene, namely, C(-318)T, A49G, and (AT)n dinucleotide repeat, with Graves' disease was demonstrated in most of the population-based investigations. On the other hand, there are few studies to reveal the association of these markers with Hashimoto's thyroiditis. A49G polymorphism was proposed to be associated with Hashimoto's thyroiditis, and C(-318)T was suggested to be not associated. The patient groups consisted of 88 patients (10 males and 78 females; mean age: 14.5 +/- 3.2 years [4.6-21.0 years]) with a previous diagnosis of Hashimoto's thyroiditis and 112 euthyroid volunteers (51 males and 61 females; mean age: 14.1 +/- 2.9 years [5.2-18 years]). The frequency of A/G (A49G) genotype was high and statistically significant in patients with Hashimoto's thyroiditis in comparison with the control group. Although the frequency of C/T [C(-318)T] genotype is not significantly high in children with Hashimoto's thyroiditis according to the control group, the risk of Hashimoto's thyroiditis in A/G genotype group was 4.66 times greater than the group with A/A genotype. In this study, we documented that the A49G polymorphism might increase the susceptibility for Hashimoto's thyroiditis.

Evaluation of bone turnover in epileptic children using oxcarbazepine.

This study evaluated the effects of oxcarbazepine monotherapy on bone turnover in prepubertal and pubertal children. Thirty-four newly diagnosed pediatric patients with normal bone mineral density, serum biochemical markers of bone formation, and hormonal markers participated. Levels of 25-hydroxyvitamin D were significantly decreased after therapy compared with baseline values. Levels of gamma-glutamyl transferase, phosphorus, alkaline phosphatase, osteocalcin, parathyroid hormone, and calcitonin had increased. However, only changes in osteocalcin and gamma-glutamyl transferase levels were statistically significant compared with baseline values. Drug-induced osteopenia was evident in 3 patients with z scores of bone-mineral density less than -2.0, whereas these patients had z scores of less than -1.5 before treatment. Although 18 months of oxcarbazepine treatment exerted slightly adverse effects on bone metabolism, the effect seems insignificant in children with normal bone-mineral density. Although alterations in bone metabolism do not always suffice to explain the decrease in bone-mineral metabolism, we think that patients with osteopenia before the initiation of oxcarbazepine therapy should be followed carefully, especially in long-term treatment.