Gülay Karagüzel

Cleidocranial dysplasia: a case report.

Cleidocranial dysplasia (CCD) is a rare autosomal dominant skeletal disease. CCD is caused by mutation in the gene on 6p21 encoding transcription factor CBFA1, i.e. runt−related transcription factor 2(RUNX2). The disease is characterized by a persistently open anterior fontanelle and skull sutures, hypoplastic or aplastic clavicles, dental abnormalities, short stature, a wide pubic symphysis, and a variety of other skeletal changes. A major finding of CCD is hypoplasia or aplasia of clavicular bones resulting in the ability of the patient to approximate the shoulders. Delayed closure of the anterior fontanelle and of metopic sutures causes frontal bossing. We report a case of CCD in a 3.5−yearold boy who referred to our clinic because of an unclosed anterior fontanelle and emphasize the importance of clinical findings in CCD. Conflict of interest:None declared.

Diabetes care, glycemic control, complications, and concomitant autoimmune diseases in children with type 1 diabetes in Turkey: a multicenter study.

Objective: Epidemiologic and clinical features of type 1 diabetes mellitus (T1DM) may show substantial differences among countries. The primary goal in the management of T1DM is to prevent micro- and macrovascular complications by achieving good glycemic control. The present study aimed to assess metabolic control, presence of concomitant autoimmune diseases, and of acute and long-term complications in patients diagnosed with T1DM during childhood and adolescence. The study also aimed to be a first step in the development of a national registry system for T1DM, in Turkey. Methods: Based on hospital records, this cross-sectional, multicenter study included 1 032 patients with T1DM from 12 different centers in Turkey, in whom the diagnosis was established during childhood. Epidemiological and clinical characteristics of the patients were recorded. Metabolic control, diabetes care, complications, and concomitant autoimmune diseases were evaluated. Results: Mean age, diabetes duration, and hemoglobin A1c level were 12.5±4.1 years, 4.7±3.2 years, and 8.5±1.6%, respectively. Acute complications noted in the past year included ketoacidosis in 5.2% of the patients and severe hypoglycemia in 4.9%. Chronic lymphocytic thyroiditis was noted in 12%, Graves’ disease in 0.1%, and celiac disease in 4.3% of the patients. Chronic complications including neuropathy, retinopathy, and persistent microalbuminuria were present in 2.6%, 1.4%, and 5.4% of the patients, respectively. Diabetic nephropathy was not present in any of the patients. Mean diabetes duration and age of patients with neuropathy, retinopathy and microalbuminuria were significantly different from the patients without these long-term complications (p<0.01). A significant difference was found between pubertal and prepubertal children in terms of persistent microalbuminuria and neuropathy (p=0.02 and p<0.001, respectively). Of the patients, 4.4% (n:38) were obese and 5% had short stature; 17.4% of the patients had dyslipidemia, and 14% of the dyslipidemic patients were obese. Conclusions: Although the majority of the patients in the present study were using insulin analogues, poor glycemic control was common, and chronic complications were encountered. Conflict of interest:None declared.

Adrenal hemorrhage in newborns: a retrospective study.

BackgroundAdrenal hemorrhage (AH) is a relatively uncommon condition in neonates. This study aimed to review the clinical, laboratory and ultrasonographic findings of AH in newborns.MethodsThe medical records of 13 newborns with AH who had been admitted to our neonatal intensive care unit were retrospectively reviewed.ResultsOf the 13 newborns with AH, 8 (62%) were term and 10 (77%) were male babies. Clinical presentations included neonatal jaundice (85%), paleness and/or flank mass (38%), discoloration of the scrotum (15%), and hypotonia/lethargy or hypotension (8%). Five newborns had anemia and four had adrenal insufficiency. Adrenal insufficiency was observed in 80% of the premature infants with AH. AH occurred on the right side in 9 patients (69%). The most predisposing cause of AH was disseminated intravascular coagulation secondary to sepsis or perinatal hypoxia in preterm infants, and large for gestational age in term infants. Ultrasonography (USG) revealed a hypoechoic mass in 7 newborns (54%), a mixed solid-liquid mass in 5 (38%), and an echogenic mass (8%) in 1. Hemorrhage disappeared within 8.6±4.5 (4–16) weeks.ConclusionsAH occurs in the newborns with unexplained jaundice. Adrenal insufficiency is more frequent in preterm than in mature infants. Abdominal USG is required to determine AH in a newborn with swelling and bluish discoloration of the scrotum. Serial USG is the best modality for monitoring AH to prevent unnecessary surgery.

Effects of Vitamin D Receptor Gene Polymorphisms on Susceptibility to Disease and Bone Mineral Density in Turkish Patients with Type 1 Diabetes Mellitus

ABSTRACT Background: Vitamin D receptor (VDR) gene is regarded as one of the candidate genes for type 1 diabetes mellitus (T1D) susceptibility and of some genetic factors involved in the development of osteoporosis in this group. Study design: We characterized the VDR gene polymorphism (BsmI, ApaI, TaqI, FokI and Cdx-2 binding site) in a group of Turkish patients with T1D (n=90) and correlated respective VDR genotypes with the bone mass and some parameters of bone turnover. Results: There were no differences in the genotype frequencies of the BsmI, ApaI, TaqI and Cdx-2 polymorphisms in patients and control subjects. We found a significantly higher prevalence of the F allele/the FF genotype in the patients compared to controls (p=0,0031, odds 1.96 (1,27-3,01)). We observed no difference in markers of bone turnover (Serum levels of osteocalcin, PINP and alkaline phosphatase, urinary levels of calcium/creatinine and N-telopeptid) among different VDR genotypes. No correlation was found between VDR polymorphisms and DEXA measurements of these patients. Conclusions: Although the FF genotype was found to be a risk factor in a Turkish population, elucidation of this result is necessary in other larger study groups drawn from the same ethnic population.

Screening of diabetes, thyroid, and celiac diseases-related autoantibodies in a sample of Turkish children with type 1 diabetes and their siblings

OBJECTIVE The purpose of this study was to investigate the presence of diabetes, thyroid, and celiac diseases (CD)-related autoantibodies in children with type 1 diabetes (DM1) and their siblings. MATERIALS AND METHODS The study population included 57 children with DM1, aged 11.7+/-4.5 years and their 89 healthy siblings, aged 11.0+/-5.4 years. Autoantibodies to glutamic acid decarboxylase (GAD65), islet cell (ICAs), insulin (IAAs), antiendomisial antibody (EMA), thyroid peroxidase, thyroglobulin, and thyrotropin receptor antibodies were studied both in diabetic patients and their siblings. RESULTS The frequencies of GAD65, ICAs and IAAs positivity were found to be 63.2, 56.1 and 84.2% in patients with DM1 and 53.9, 24.4 and 3.4% in their siblings, respectively. The frequencies of autoimmune thyroid diseases (ATD) as determined by positive thyroid-related autoantibodies were 38.6 and 21.4% (p=0.024) among patients with DM1 and siblings, respectively. Subclinical hypothyroidism or hyperthyroidism was detected in 5.3% of patients with DM1 but in none of their siblings. EMA was positive in 3.5% of diabetic patients and 1.1% of their siblings. CONCLUSIONS Our findings supported the view that children with DM1 should be screened annually for ATD. Relatively lower frequency of CD in the present study indicated that screening for CD-related autoantibodies might be postponed to older ages in asymptomatic patients. The present findings also suggested that the screening for diabetes- (especially GAD65) and thyroid diseases-related autoantibodies in siblings may ensure some useful information about the clinical course.

Reference intervals for thyrotropin and thyroid hormones and ultrasonographic thyroid volume during the neonatal period

Objective. To determine thyrotropin (TSH) and thyroid hormones reference ranges in healthy term newborns during the neonatal period and to assess the ranges of thyroid volume in newborns using ultrasound scanning. Methods. Blood samples were collected from 296 healthy newborns at birth (cord; n: 47) and before feeding on the 1st, 3rd, 5th, 7th, 10th, 14th, and 28th days of life. The levels of TSH and thyroid hormones of the newborns were then compared with results from 50 healthy adults. Thyroid ultrasonography (USG) was performed by the same radiologist on 38 newborns aged 10 days. Results. TSH and thyroid hormone levels in newborns were statistically higher than those in adults for each day (p < 0.001). Serum TSH concentration on the 1st day of life was higher than at other times (p < 0.001). Mean TSH concentration reverted to the cord level at the 5th or 7th day of life (p > 0.05). TSH levels were no higher than 10 mIU/ml after 2 weeks postnatal age. There was no correlation between hormone levels and Ponderal index (PI), birth weight, gender, or delivery type. Mean thyroid volume was 0.72 ± 0.24 ml (0.36–1.62 ml). Conclusions. We conclude that our results are important for CH screening regarding time-dependent changes of TSH and thyroid hormones besides diagnosis of thyroid hypoplasia or hyperplasia.

The effects of antiepileptic drugs on the relationships between leptin levels and bone turnover in prepubertal children with epilepsy

Abstract Antiepileptic drugs (AED) had an effect on bone metabolism in children. This study was conducted in order to determine the relationships between serum leptin levels, bone mineral density (BMD) and bone turnover markers in epileptic children. Fifty-three patients were treated with valproic acid (VPA) and 23 with carbamazepine (CBZ) monotherapy; 50 healthy children were included in the study as controls. Serum alkaline phosphatase (ALP) and cross-linked C-telopeptide (CTx) levels were statistically signifi cantly higher in the CBZ group than in the VPA group and the control group (p<0.0001, p<0.010, respectively). Serum osteocalcin and ALP levels were signifi cantly lower in the VPA group than in the control group (p<0.012, p<0.030, respectively). Although we found slightly higher serum leptin levels in both the CBZ and VPA groups, they were not signifi cantly different from the control group (P>0.05). We demonstrated that the markers of bone formation and resorption increased with CBZ and decreased with VPA treatment without affecting BMD and vitamin D levels in prepubertal epileptic children.

Short-term effects of budesonide, nedocromil sodium and salmeterol on bronchial hyperresponsiveness in childhood asthma.

Abstract Background: The effects of budesonide, nedocromil sodium and salmeterol on bronchial hyperresponsiveness were determined over a period of 3 weeks.

The effects of topiramate and valproate therapy on insulin, c-peptide, leptin, neuropeptide Y, adiponectin, visfatin, and resistin levels in children with epilepsy

PURPOSE Antiepileptic drugs may affect the endocrine system. We investigated the effects of valproic acid and topiramate on the levels of insulin, c-peptide and adipocytokines in pre-pubertal patients with idiopathic partial and generalized epilepsy. METHODS Forty-one children with epilepsy were included. The patients were divided into two groups (valproic acid; n = 21, topiramate; n = 20). The weight, height, body mass index and homeostasis model assessment of insulin resistance (HOMA-IR) were recorded and insulin, c-peptide, leptin, neuropeptide Y, adiponectin, visfatin and resistin levels were determined at 0, 6 and 12 months of therapy. RESULTS In the valproate group, weight and height increased significantly. Seven of 21 patients were overweight at the end of one year. Leptin was higher in the overweight subgroup. Although insulin and HOMA-IR increased (p < 0.05), none of the patients showed hyperinsulinism or IR. Resistin had decreased at the 6th and 12th months (p < 0.05). In the topiramate group, some statistically nonsignificant changes were demonstrated. CONCLUSION The mechanisms behind valproate and topiramate-related weight control are still unclear, especially in children. Valproate and topiramate affect the weight, BMI, and insulin, leptin and adipocytokine levels in prepubertal children. We suggest that further studies including more patients with a long follow-up period are necessary to draw a firm conclusion regarding an association between the treatment with these drugs and the levels of leptin, insulin and adipocytokines.

The Etiology and Clinical Features of Non-CAH Gonadotropin-Independent Precocious Puberty: A Multicenter Study

AIM The causes of gonadotropin-independent precocious puberty are diverse, and often have overlapping clinical and biochemical features. With the exception of congenital adrenal hyperplasia (CAH), disorders that cause gonadotropin-independent precocious puberty (GIPP) are uncommon. The literature is devoid of any large-scale studies on the etiologic distribution of GIPP. The aim of this study was to determine the frequency of each etiology in a cohort of patients with GIPP (excluding those with CAH), and to evaluate the clinical and laboratory features of these patients. MATERIALS AND METHODS This multicenter, nationwide web-based study collected data on patients who presented with non-CAH GIPP in Turkey. RESULTS Data were collected for 129 patients (102 girls and 27 boys) from 29 centers. Based on the data collected, the estimated prevalence of non-CAH GIPP in the studied population was 14 in 1 000 000 children. Functional ovarian cyst was the most common etiology, accounting for 37% of all cases, followed by McCune-Albright syndrome (MAS) (26%). Among the patients with MAS, 11.7% had fibrous dysplasia, 32.3% had café-au-lait spots, and 52.9% had both. Human chorionic gonadotrophin-secreting tumors included choriocarcinoma of the liver, hepatoblastoma, and germ cell tumors of the sellar-suprasellar region and mediastinum. Patients with adrenocortical tumors presented at an earlier age than those with other etiologies. Ovarian tumors included mature cystic teratoma, dysgerminoma, juvenile granulosa tumor, and steroid cell tumor. Despite overlapping features, it was possible to identify some unique clinical and laboratory features associated with each etiology. CONCLUSION This largest cohort of patients with non-CAH GIPP to date yielded an estimation of the frequency of non-CAH GIPP in the general pediatric population and showed that girls were affected at a rate 4-fold greater than that of boys owing to functional ovarian cysts and MAS, which were the two most common etiologies. The data collected also provided some unique characteristics associated with each etiology.