ISSN: 1308-5727 | E-ISSN: 1308-5735
Volume : 8 Issue : 3 Year : 2024

Abstracting & Indexing
Turkish Society for Pediatric Endocrinology and Diabetes
Volume: 8  Issue: 3 - 2016

Pages I - XI

2.Environmental Contaminants and Pancreatic Beta-Cells
Gabriel Fabricio, Ananda Malta, Abalo Chango, Paulo Cezar De Freitas Mathias
doi: 10.4274/jcrpe.2812  Pages 257 - 263
Despite health policies as well as clinical and research efforts, diabetes prevalence is still rising around the world. A multitude of causes have been suggested for this increase, mostly related to familial background, the occidental diet which is rich in fat/carbohydrates, and sedentary life style. Type 2 diabetes involves malfunctions of the primary pancreatic beta-cells, usually attributed to local damage; however, it can be associated with other stressful environmental agents, such as chemical contaminants from food, plastic and air, among others. Indeed, exposure to these chemical agents during perinatal and adolescent life can increase the risk of developing cardiometabolic diseases later in life. This review explores data showing which environmental chemical agents may produce injury in beta-cells and further impair the insulinotropic process of type 2 diabetes. Additionally, it points the need to also consider unusual causes of metabolic diseases, such as environmental contaminants.

3.The Relationship between Maternal Gestational Impaired Glucose Tolerance and Risk of Large-for-Gestational-Age Infant: A Meta-Analysis of 14 Studies
Hai-Qing Wang, Han-Lin Lai, Yi Li, Qi-Fei Liu, Shuang Hu, Li Li
doi: 10.4274/jcrpe.2583  Pages 264 - 269
Objective: To explore, by conducting a meta-analysis, whether gestational impaired glucose tolerance (IGT) is an independent predictor of neonatal large for gestational age (LGA) or not.
Methods: Medline, Embase, and Cochrane Library databases were searched to identify published epidemiological studies (cohort and case-control studies) investigating the association between gestational IGT and neonatal LGA. Calculations of pooled estimates were conducted in random-effect models or fixed-effects models. Heterogeneity was tested by using chi-square test and I2 statistics. Egger’s test (linear regression method) and Begg’s test (rank correlation method) were used to assess potential publication bias.
Results: Fourteen observational studies were included in the meta-analysis. The overall risk for the effect of IGT on LGA was 2.09 (1.56, 2.78). Stratified analyses showed no differences regarding different geographic regions or the analysis of overall adjusted odds ratios. No evidence of publication bias was observed in either Egger’s test or Begg’s test results.
Conclusion: Gestational IGT is an independent predictor of neonatal LGA.

4.Indices of Glucose Homeostasis in Cord Blood in Term and Preterm Newborns
Afzal Ahmad, M. S. Rukmini, Charu Yadav, Ashish Agarwal, Poornima A. Manjrekar, Anupama Hegde
doi: 10.4274/jcrpe.2819  Pages 270 - 275
Objective: According to the thrifty phenotype hypothesis, intrauterine malnutrition has a role in the etiology of type 2 diabetes. This study was planned to determine the early alterations in indices of glucose homeostasis (glucose, insulin, and cortisol) in term and preterm newborns and the correlations of glucose, insulin, and cortisol levels with insulin resistance indices.
Methods: A descriptive study comprising 35 term and 35 preterm newborns was carried out from December 2013 to June 2015. Venous cord blood was collected and plasma glucose was analyzed by the glucose oxidase-peroxidase method in an auto analyzer. Serum insulin and cortisol levels were assessed by the enzyme-linked immunosorbent assay. Homeostasis model assessment of insulin resistance (HOMA-IR), quantitative insulin sensitivity check index and glucose insulin ratio were calculated to assess insulin resistance. The data on physical and metabolic parameters were analyzed using standard tests for statistical significance.
Results: In term newborns, mean glucose and cortisol levels (83.6±17.4 mg/dL and 11.88±5.78 µg/dL, respectively) were significantly higher than those in preterm infants (70.4±15.8 mg/dL and 8.9±4.6 µg/dL, respectively). Insulin and HOMA-IR levels were found higher in preterm newborns (10.8±4.8 µIU/mL and 1.52±0.66, respectively) than in term newborns (7.9±2.7 µIU/mL and 1.19±0.29, respectively). Insulin was found to positively correlate with HOMA-IR, whereas cortisol was negatively correlated with HOMA-IR in both term and preterm newborns.
Conclusion: Higher insulin levels and HOMA-IR values in the cord blood of preterm newborns support the theory of intrauterine origin of metabolic diseases.

5.Regulatory T Cells and Vitamin D Status in Children with Chronic Autoimmune Thyroiditis
Zeynep Şıklar, Deniz Karataş, Figen Doğu, Bülent Hacıhamdioğlu, Aydan İkincioğulları, Merih Berberoğlu
doi: 10.4274/jcrpe.2766  Pages 276 - 281
Objective: It is suggested that vitamin D is one of the factors that can regulate the function of Treg cells. In this study, the relationships between Treg cells and vitamin D levels was investigated in pediatric chronic autoimmune thyroiditis (CAT) patients.
Methods: Thirty-two children with CAT and 24 healthy subjects were studied. FOXP3 expressing CD4+CD25+high Foxp3+T cells were identified as Treg cells. At diagnosis, 25-hydroxycholecalciferol (25OHD3) levels were determined in all patients. FOXP3 expression was measured before and after vitamin D replacement therapy in patients having low levels of 25OHD3.
Results: In the CAT patients, Treg cell levels did not differ from the control group, while the frequency of vitamin D deficiency was higher and FOXP3 molecule expression was lower. FOXP3 molecule expression significantly increased in CAT patients having vitamin D deficiency who were given vitamin D replacement.
Conclusion: FOXP3 expression is decreased in pediatric CAT patients. This reduction seems to be associated with vitamin D levels. Vitamin D can play a role in enhancing natural Treg cell functions.

6.Urinary Netrin-1: A New Biomarker for the Early Diagnosis of Renal Damage in Obese Children
Duygu Övünç Hacıhamdioğlu, Bülent Hacıhamdioğlu, Demet Altun, Tuba Müftüoğlu, Ferhan Karademir, Selami Süleymanoğlu
doi: 10.4274/jcrpe.2828  Pages 282 - 287
Objective: Urinary netrin-1 is a new marker to demonstrate early tubular damage. The aim of this study was to determine whether urinary netrin-1 is increased in obese children.
Methods: A total of 68 normoalbuminuric and normotensive obese patients and 65 controls were included in the study. Urine samples were collected for assessment of urinary phosphorus, sodium, potassium, creatinine, albumin, and netrin-1. Blood samples were collected for measurements of fasting glucose, insulin, lipid, phosphorus, sodium, potassium, and creatinine levels. Homeostatic model assessment insulin resistance index was calculated.
Results: Gender and age were similar between obese and control groups (12.01±3.03 vs. 11.7±3.2 years, p=0.568 and 33 vs. 35 girls, p=0.543, respectively). Obese patients had significantly higher netrin-1 excretion than the controls (841.68±673.17 vs. 228.94±137.25 pg/mg creatinine, p=0.000). Urinary netrin-1 level was significantly higher in obese subjects with insulin resistance compared to those without insulin resistance (1142±1181 vs. 604.9±589.91 pg/mg creatinine, p=0.001).
Conclusion: In normotensive and normoalbuminuric obese children, urinary netrin-1 level can increase before onset of albuminuria. Urinary netrin-1 excretion appears to be affected predominantly by insulin resistance and hyperinsulinemia. Urinary netrin-1 may be a new biomarker for determining early tubular injury in obese children.

7.Anti-Müllerian Hormone and Inhibin-A, but not Inhibin-B or Insulin-Like Peptide-3, may be Used as Surrogates in the Diagnosis of Polycystic Ovary Syndrome in Adolescents: Preliminary Results
Aylin Yetim, Çağcıl Yetim, Firdevs Baş, Oğuz Bülent Erol, Gülnaz Çığ, Ahmet Uçar, Feyza Darendeliler
doi: 10.4274/jcrpe.3253  Pages 288 - 297
Objective: Polycystic ovary syndrome (PCOS) is a common endocrine problem in adolescents with an increasing prevalence of 30%. Pursuing new biomarkers with high specificity and sensitivity in the diagnosis of PCOS in adolescents is currently an active area of research. We aimed to investigate the diagnostic value of anti-Müllerian hormone (AMH), insulin-like peptide-3 (INSL3), inhibin-A (INH-A), and inhibin-B (INH-B) in adolescents with PCOS and also to determine the association, if any, between these hormones and clinical/laboratory findings related with hyperandrogenism.
Methods: The study group comprised 53 adolescent girls aged between 14.5 and 20 years who were admitted to our outpatient clinic with symptoms of hirsutism and/or irregular menses and diagnosed as having PCOS in accordance with the Rotterdam criteria. Twenty-six healthy peers, eumenorrheic for at least two years and body mass index-matched, constituted the controls. Fasting blood samples for hormones [luteinizing hormone (LH), follicle-stimulating hormone (FSH), dehydroepiandrosterone-sulfate (DHEAS), androstenedione (D4-A), total/free testosterone (T/fT), sex hormone binding globulin (SHBG), AMH, INSL3, INH-A, INH-B] were drawn after an overnight fast.
Results: In the PCOS group, 83% of the subjects were oligomenorrheic/amenorrheic and 87% had hirsutism. The LH, LH/FSH ratio, total T, fT, free androgen-index (FAI), DHEAS levels were significantly higher (p=0.005, p=0.042, p=0.047, p<0.001, p=0.007, p=0.014, respectively) and SHBG was significantly lower (p=0.004) in PCOS patients as compared to the controls. Although the INSL-3 and INH-B levels showed no difference between the groups (p>0.05), AMH and INH-A levels were found to be significantly higher in the PCOS group compared to the controls (p<0.001, p<0.001, respectively). In multiple linear regression analysis, WC SDS (p=0.028), logD4-A (p=0.033), logSHBG (p=0.031), and total ovarian volume (p=0.045) had significant effects on AMH levels, and LH (p=0.003) on INH-A levels. In receiver-operating characteristic analysis, the cut-off values for AMH and INH-A were 6.1 ng/mL (sensitivity 81.1%) and 12.8 pg/mL (sensitivity 86.8%), respectively, to diagnose PCOS. When AMH and INH-A were used in combination, the sensitivity (96.2%) increased.
Conclusion: INSL3 and INH-B were not found to have diagnostic value in adolescents with PCOS. On the other hand, it was shown that INH-A could be used as a new diagnostic biomarker in addition to AMH.

8.Hidden Toxicity in Neonatal Intensive Care Units: Phthalate Exposure in Very Low Birth Weight Infants
Atalay Demirel, Asuman Çoban, Şükran Yıldırım, Canan Doğan, Rukiye Sancı, Zeynep İnce
doi: 10.4274/jcrpe.3027  Pages 298 - 304
Objective: To determine exposure to endocrine-disrupting phthalates in preterm infants in neonatal intensive care units (NICU). Methods: Urine samples (n=151) from 36 preterm infants (<32 weeks of gestation and/or <1500 g of birth weight) were collected on the first 3 days of admission to the NICU and biweekly thereafter. Diethylhexyl phthalate contents of indwelling medical devices used in various procedures and the concentrations of phthalate metabolites in the urine samples were analyzed. The relationships between urinary excretion, exposure intensity, postnatal age and birth weight were examined.
Results: The mean gestational age and mean birth weight of the study infants were 28.9±1.5 weeks and 1024±262 g, respectively. Diethylhexyl phthalate was detected in umbilical catheters, endotracheal tubes, nasogastric tubes, and nasal cannula. Monoethylhydroxyhexyl phthalate (MEHHP) was the most frequently detected metabolite (81.4%); its concentration increased during the first 4 weeks and then started to decrease but never disappeared. Patients who did not need indwelling catheters (except nasogastric tubes) after 2 weeks were classified as group 1 and those who continued to have indwelling catheters as group 2. Although not of statistical significance, MEHHP levels decreased in group 1 but continued to stay high in group 2 (in the 4th week, group 1: 65.9 ng/mL and group 2: 255.3 ng/mL). Levels of MEHHP in the first urinary samples were significantly higher in infants with a birth weight <1000 g (<1000 g: 63.2±93.8 ng/mL, ?1000 g: 10.9±22.9 ng/mL, p=0.001).
Conclusion: Phthalate metabolites were detected even in the first urine samples of very low birth weight newborns. Phthalate levels were higher in the first weeks of intensive invasive procedures and in preterm infants with a birth weight less than 1000 g. MEHHP was the most frequently detected metabolite and could be a suitable biomarker for the detection of phthalate exposure in preterm infants.

9.The Growth Characteristics of Patients with Noonan Syndrome: Results of Three Years of Growth Hormone Treatment: A Nationwide Multicenter Study
Zeynep Şıklar, Mikayir Genens, Şükran Poyrazoğlu, Firdevs Baş, Feyza Darendeliler, Rüveyde Bundak, Zehra Aycan, Şenay Savaş Erdeve, Semra Çetinkaya, Ayla Güven, Saygın Abalı, Zeynep Atay, Serap Turan, Cengiz Kara, Gülay Can Yılmaz, Nesibe Akyürek, Ayhan Abacı, Gamze Çelmeli, Erkan Sarı, Semih Bolu, Hüseyin Anıl Korkmaz, Enver Şimşek, Gönül Çatlı, Muammer Büyükinan, Atilla Çayır, Olcay Evliyaoğlu, Pınar İşgüven, Tolga Özgen, Nihal Hatipoğlu, Atilla Halil Elhan, Merih Berberoğlu
doi: 10.4274/jcrpe.3013  Pages 305 - 312
Objective: Noonan syndrome (NS) is a multisystem disorder, and short stature is its most striking manifestation. Optimal growth hormone (GH) treatment for NS is still controversial. In this study, using a nationwide registration system, we aimed to evaluate the growth characteristics and the clinical features of NS patients in Turkey and their growth response to GH treatment.
Methods: Children and adolescents with a diagnosis of NS were included inthe study. Laboratory assessment including standard GH stimulation test results were evaluated. Height increment of patients with or without GH treatment were analyzed after three years of therapy.
Results: A total of 124 NS patients from different centers were entered in the web-based system. Short stature and typical face appearance were the most frequently encountered diagnostic features of our patients. Of the 84 patients who were followed long-term, 47 hadreceived recombinant human GH (rhGH). In this group of 47 patients, height standard deviation score (HSDS) increased from -3.62±1.14 to -2.85±0.96 after three years of therapy, indicating significant differences from the patients who did not receive GH treatment. PTPN11 gene was analyzed in 61 patients, and 64% of these patients were found to have a mutation. HSDS at admission was similar in patients with or without PTPN11 gene mutation.
Conclusion: A diagnosis of NS should be kept in mind in all patients with short stature showing systemic clinical findings. GH therapy is effective for improvement of short stature especially in the first two years of treatment. Further studies are needed for optimisation of GH therapy and evaluation of final height data in NS patients.

10.Soluble Endoglin Level Increase Occurs Prior to Development of Subclinical Structural Vascular Alterations in Diabetic Adolescents
Hamdi Cihan Emeksiz, Aysun Bideci, Çağrı Damar, Betül Derinkuyu, Nurullah Çelik, Esra Döğer, Özge Yüce, Mehmet Cüneyt Özmen, Mahmut Orhun Çamurdan, Peyami Cinaz
doi: 10.4274/jcrpe.2906  Pages 313 - 320
Objective: Soluble endoglin (S-endoglin) has been implicated as a potential marker of endothelial dysfunction (ED) and was reported to be elevated in diabetic adults, correlating with the severity of diabetic vasculopathy. However, circulating S-endoglin and its association with other markers of ED have not been formerly analyzed in the first decade of diabetes onset in adolescents with type 1 diabetes mellitus (T1DM).
Methods: Fifty-eight adolescents with moderately/poorly controlled T1DM were included in this study and twenty-nine healthy adolescents served as controls. The diabetic group was divided into two groups based on the presence of microalbuminuria, as the microalbuminuria group (n=15) and the normoalbuminuria group (n=43). Functional vascular alterations were evaluated by measuring serum S-endoglin and plasma nitric oxide (NO) concentrations, the flow-mediated dilatation (FMD) of the brachial artery. Carotid intima media thickness (CIMT) was measured for evaluation of structural vascular alterations.
Results: The S-endoglin and NO levels of both microalbuminuria and normoalbuminuria groups were higher than those of the control group (for S-endoglin, p=0.047 and p<0.001; for NO, p=0.004 and p=0.006, respectively). The FMD percent was lower in the microalbuminuria group compared to the normoalbuminuria and control groups (p=0.036 and p=0.020, respectively). There were negative correlations between S-endoglin concentration and FMD percent (r=-0.213, p=0.051) and between serum S-endoglin concentration and albumin excretion rate (r=-0.361, p=0.005). No significant differences were found in CIMT among any of the groups (p=0.443).
Conclusion: In adolescents with T1DM, S-endoglin concentrations might increase in parallel to the deterioration in endothelial function before subclinical structural vascular alterations become evident.

11.Adding Multiple Adipokines into the Model do not Improve Weight Gain Prediction by Leptin Levels in Newborns
Consuelo Treviño-Garza, Cynthia M. Estrada-Zúñiga, Leonardo Mancillas-Adame, Laura Villarreal-Martínez, Jesús Z. Villarreal-Pérez, Isaías Rodríguez-Balderrama, Fernando F. Montes-Tapia, Manuel E. de la O. Cavazos
doi: 10.4274/jcrpe.2693  Pages 321 - 324
Objective: Most adipose tissue programming is realized in early life. Also, the postnatal three months, rather than the later phases of infancy, may be more relevant in the development of an adverse cardiometabolic risk profile. The adipokines phenotype, as a predictor of early-life weight gain, has been recently explored in cord blood. To determine whether in addition to leptin levels in cord samples, adiponectin, interleukin-6 (IL-6), monocyte chemoattractant protein-1 (MCP-1), resistin, plasminogen activator inhibitor-1 (PAI-1), and tumor necrosis factor alpha (TNF-?) levels improve weight gain prediction during the first three months of life.
Methods: Adiponectin, IL-6, MCP-1, leptin, resistin, PAI-1, and TNF-? were measured by multiplex immunoassay in a subsample of 86 healthy term newborns.
Results: Leptin levels significantly predicted weight gain at 3 months of follow-up (r2=0.09, p=0.006). In the multivariate analysis, including additional adipokines in the model, stepwise or all at once, did not increase the prediction of weight gain after the first three months of life.
Conclusion: Adding adiponectin, IL-6, MCP-1, resistin, PAI-1, and TNF-? to the prediction model of weight gain in healthy newborns did not prove to be useful. It is probable that their relative contribution to weight gain is not important. Only leptin was relevant as a predictor of weight gain at the 3-month endpoint.

12.The Association between Serum 25-Hydroxy Vitamin D Level and Urine Cathelicidin in Children with a Urinary Tract Infection
Duygu Övünç Hacıhamdioğlu, Demet Altun, Bülent Hacıhamdioğlu, Ferhat Çekmez, Gökhan Aydemir, Mustafa Kul, Tuba Müftüoğlu, Selami Süleymanoğlu, Ferhan Karademir
doi: 10.4274/jcrpe.2563  Pages 325 - 329
Objective: Cathelicidin is an important antimicrobial peptide in the urinary tract. Cathelicidin expression is strongly stimulated by 1,25-dihydroxy vitamin D in epithelial cells, macrophages/monocytes, and neutrophils. Vitamin D and cathelicidin status in children with urinary tract infection (UTI) caused by Escherichia coli is unknown. To establish the relationship between serum vitamin D and urine cathelicidin levels in children with a UTI caused by Escherichia coli.
Methods: Serum 25-hydroxy vitamin D and urine cathelicidin levels were measured in 36 patients with UTI (mean age 6.8±3.6 years, range: 0.25-12.6 years) and 38 controls (mean age 6.3±2.8 years, range: 0.42-13 years).
Results: There were no significant differences in urine cathelicidin levels between the study and control groups (p>0.05). Eight (22.2%) patients in the study group and 21 (58.3%) children in the control group were found to have sufficient vitamin D (?20 ng/mL). Patients with sufficient vitamin D had higher urine cathelicidin levels than the controls with sufficient vitamin D (respectively 262.5±41.1 vs. 168±31.6 ng/mL, p=0.001). There were no significant differences between the patients and controls with insufficient vitamin D (p>0.05).
Conclusion: The children with vitamin D insufficiency may not be able to increase their urine cathelicidin level during UTI caused by Escherichia coli. There is a need of prospective studies in order to prove a beneficial effect of vitamin D supplementation for the restoration of cathelicidin stimulation and consequently for prevention of UTI recurrence.

13.Endocrine Dysfunctions in Patients with Inherited Metabolic Diseases
Şahin Erdöl, Halil Sağlam
doi: 10.4274/jcrpe.2288  Pages 330 - 333
Objective. Inherited metabolic diseases (IMDs) can affect many organ systems, including the endocrine system. There are limited data regarding endocrine dysfunctions related to IMDs in adults, however, no data exist in pediatric patients with IMDs. The aim of this study was to investigate endocrine dysfunctions in patients with IMDs by assessing their demographic, clinical, and laboratory data.
Methods: Data were obtained retrospectively from the medical reports of patients with IMDs who were followed by the division of pediatric metabolism and nutrition between June 2011 and November 2013.
Results: In total, 260 patients [139 males (53%) and 121 females (47%)] with an IMD diagnosis were included in the study. The mean age of the patients was 5.94 (range; 0.08 to 49) years and 95.8% (249 of 260 patients) were in the pediatric age group. Growth status was evaluated in 258 patients and of them, 27 (10.5%) had growth failure, all cases of which were attributed to non-endocrine reasons. There was a significant correlation between growth failure and serum albumin levels below 3.5 g/dL (p=0.002). Only three of 260 (1.1%) patients had endocrine dysfunction. Of these, one with lecithin-cholesterol acyltransferase deficiency and another with Kearns-Sayre syndrome had diabetes, and one with glycerol kinase deficiency had glucocorticoid deficiency.
Conclusion: Endocrine dysfunction in patients with IMDs is relatively rare. For this reason, there is no need to conduct routine endocrine evaluations in most patients with IMDs unless a careful and detailed history and a physical examination point to an endocrine dysfunction.

14.The Role of Active Video-Accompanied Exercises in Improvement of the Obese State in Children: A Prospective Study from Turkey
Fatma Duman, Mehmet Hanifi Kokaçya, Esra Doğru, Nihan Katayıfcı, Özden Canbay, Fatma Aman
doi: 10.4274/jcrpe.2284  Pages 334 - 340
Objective: The aim of this study was to determine the effects of active video games and music-accompanied aerobic and callisthenic exercises on body mass index (BMI), body fat ratio, physical performance tests, psychosocial status, and self-respect in overweight and obese adolescents.
Methods: Fifty (21 males and 29 females) slightly overweight and obese participants with no chronic disorder and of an average age of 12.16±0.99 years were included in the study. The percentile values for BMI, triceps skinfold thickness, waist circumference measurements, and physical performance tests were evaluated. The effects of obesity on psychological wellness were evaluated using the depression scale for children (DSC) and the Piers-Harris Children’s Self-Concept Scale for self-esteem. Following these evaluations, the participants were subjected to an exercise program in five groups of 10 people, 3 days a week for a duration of 8 weeks. Each exercise session lasted 45 minutes. Participants were re-evaluated at the end of the exercise program. The data collected both before and after the exercise program were analyzed using the SPSS 18.0 program.
Results: According to BMI reference values, 28% of the 50 participants (n=14; 6 males and 8 females) were assessed to be overweight and 72% to be obese (n=36; 15 males and 21 females). Following the exercise program, 14% of the participants (n=7; 3 males and 4 females) were assessed as normal, 46% (n=23; 14 males and 9 female) as slightly overweight, and 40% (n=20; 4 male and 16 female) as obese. It was determined that the decrease in BMI values (p<0.05) was higher in male participants than in female participants and that the frequency of obesity was higher in the females. A statistically significant decrease in BMI values was found after the exercise program (p<0.01). Following the exercise program, statistically significant differences have also been observed in the self-esteem (p<0.01), psychological wellness (p=0.025), triceps skinfold thickness, as well as in waist circumference and BMI values of the participants compared to the pre-exercise phase (p<0.01).
Conclusion: An exercise program applied with active video games was found to have positive effects on the obese state as well as on the psychosocial status and self-esteem of obese individuals, indicating that exercise and physical activity have an important role in improvement of the obese state in childhood as well as having positive contributions to self-esteem and psychological wellness state.

15.Identification and Functional Characterization of a Calcium-Sensing Receptor Mutation in an Infant with Familial Hypocalciuric Hypercalcemia
Anna Papadopoulou, Evangelia Gole, Katerina Melachroinou, Christos Meristoudis, Tania Siahanidou, Anastasios Papadimitriou
doi: 10.4274/jcrpe.2800  Pages 341 - 346
Familial hypocalciuric hypercalcemia (FHH) is an autosomal dominant disorder, associated with inactivating mutations of the calcium-sensing receptor (CaSR). To evaluate the functional significance of a CaSR mutation, identified in a young infant who presented with hypercalcemia and hypocalciuria. The CaSR gene coding sequences were analyzed by polymerase chain reaction amplification and direct sequencing analysis. The mutation identified was introduced by site-directed mutagenesis into a wild-type (WT) CaSR plasmid, and human embryonic kidney 293 T cells were transfected with either the WT or mutant CaSR. The function of the mutated CaSR protein was analyzed by evaluating the free intracellular calcium [(Ca2+)i] response after challenge with extracellular calcium (Ca2+). We identified a heterozygous mutation c.772_773delGTinsA in exon 4 resulting in the substitution of amino acid valine (Val) with amino acid arginine (Arg) and the premature pause of the translation 46 amino acids later (Val258ArgfsTer47). Functional assay showed that cells transfected with the mutant CaSR had a significantly poorer response to extracellular Ca2+ stimulation compared with the WT. We have shown that the c.772_773delGTinsA mutation causes a significant alteration of CaSR function leading to features of FHH in an affected young infant since the first months of life.

16.Fluoxetine-Induced Hypoglycaemia in a Patient with Congenital Hyperinsulinism on Lanreotide Therapy
Dinesh Giri, Victoria Price, Zoe Yung, Mohammed Didi, Senthil Senniappan
doi: 10.4274/jcrpe.2818  Pages 347 - 350
Antidepressant drugs are reported to cause alterations in blood glucose homeostasis in adults with diabetes mellitus. We report a patient with persistent congenital hyperinsulinism (CHI) who developed recurrent hypoglycaemia following fluoxetine therapy. This 15-year-old girl was initially managed with diazoxide therapy. She developed troublesome hypertrichosis, which affected her quality of life adversely. Diazoxide was then slowly weaned and stopped with the introduction of octreotide, to which she responded well. Subcutaneous lanreotide (long-acting somatostatin analogue) was subsequently commenced (30 mg, once monthly) as injecting octreotide multiple times a day was proving to be difficult for the patient. The continuous blood glucose monitoring on monthly lanreotide injections revealed good glycaemic control. Six months later, she developed depression due to psychosocial problems at school. She was started on fluoxetine by the psychiatry team. She subsequently developed recurrent symptomatic hypoglycaemic episodes (blood glucose <3.5 mmol/L) and fluoxetine was discontinued, following which the hypoglycaemic episodes resolved within a week. Fluoxetine has been associated with hypoglycaemia in patients with diabetes mellitus. We report, for the first time, hypoglycaemia secondary to fluoxetine in a patient with CHI.

17.Gonadoblastoma and Papillary Tubal Hyperplasia in Ovotesticular Disorder of Sexual Development
Enver Şimşek, Çiğdem Binay, Meliha Demiral, Baran Tokar, Sare Kabukçuoğlu, Melek Üstün
doi: 10.4274/jcrpe.2705  Pages 351 - 355
Ovotesticular disorder of sexual development (DSD), formerly known as true hermaphroditism, is a rare form of DSD in which both testicular and ovarian tissues are present in the same individual either in a single gonad (ovotestis) or in opposite gonads with a testis and an ovary on each side. The diagnosis of ovotesticular DSD is based solely on the presence of ovarian and testicular tissue in the gonad and not on the characteristics of the internal and external genitalia, even if ambiguous. Herein, we report two patients with ovotesticular DSD-one presenting with ambiguous genitalia on the third day after birth and the other with short stature and primary amenorrhea in adolescence. Clinical and histopathological investigation revealed a sex-determining region on the Y chromosome (SRY)-positive 46,XX karyotype and bilateral ovotestes in case 1 and a 46,XY karyotype with hypergonadotropic hypogonadism and a streak gonad in one ovotestis with dysgerminoma, gonadoblastoma, and papillary tubal hyperplasia in the contralateral ovotestis in case 2. Laparoscopic examination and gonadal biopsy for histopathological diagnosis remain the cornerstones for a diagnosis of ovotesticular DSD. Moreover, SRY positivity in a 46,XX patient, a 46,XY karyotype, an intra-abdominal gonad, and the age of patient at the time of diagnosis are predictive risk factors for the development of gonadoblastoma and/or dysgerminoma in ovotesticular DSD.

18.Corticosterone Methyl Oxidase Deficiency Type 1 with Normokalemia in an Infant
Ala Üstyol, Mehmet Emre Atabek, Norman Taylor, Matthew Chun-wing Yeung, Angel O. K. Chan
doi: 10.4274/jcrpe.2824  Pages 356 - 359
Isolated aldosterone synthase deficiency may result in life-threatening salt-wasting and failure to thrive. The condition involves hyperkalemia accompanying hyponatremia. Two types of aldosterone synthase deficiency may be observed depending on hormone levels: corticosterone methyl oxidase type 1 (CMO 1) and CMO 2. Herein, we describe a Turkish infant patient with aldosterone synthase deficiency who presented with failure to thrive and salt wasting but with normal potassium levels. Urinary steroid characteristics were compatible with CMO I deficiency. Diagnosis of aldosterone synthase deficiency was confirmed by mutational analysis of the CYP11B2 gene which identified the patient as homozygous for two mutations: c.788T>A (p.Ile263Asn) and c.1157T>C (p.Val386Ala). Family genetic study revealed that the mother was heterozygous for c.788T>A and homozygous for c.1157T>C and the father was heterozygous for both c.788T>A and c.1157T>C. To the best of our knowledge, this is only the second Turkish case with a confirmed molecular basis of type 1 aldosterone synthase deficiency. This case is also significant in showing that spot urinary steroid analysis can assist with the diagnosis and that hyperkalemia is not necessarily part of the disease.

19.Pyridoxine-Responsive Seizures in Infantile Hypophosphatasia and a Novel Homozygous Mutation in ALPL Gene
Banu Güzel Nur, Gamze Çelmeli, Esra Manguoğlu, Erdoğan Soyucen, İffet Bircan, Ercan Mıhçı
doi: 10.4274/jcrpe.2798  Pages 360 - 364
Hypophosphatasia is a rare inherited disorder of bone and mineral metabolism caused by a number of loss-of-function mutations in the ALPL gene. It is characterized by defective bone and tooth mineralisation associated with low serum and bone alkaline phosphatase activity. The clinical presentation of this disease is extremely variable. For this reason, the diagnosis can be difficult and is often missed out or delayed. Hypophosphatasia is classified into subtypes based on the age of onset and clinical features. The clinical severity is associated with the age at diagnosis and the lack of tissue-nonspecific alkaline phosphatase activity; the severe forms of hypophosphatasia are primarily perinatal and infantile forms. Severe forms may present with many neurological problems such as seizures, hypotonia, irritability. Herein, we report the case of an infantile hypophosphatasia patient who presented with pyridoxine-responsive seizures and a novel homozygous mutation in the ALPL gene was detected. There is a limited number of hypophosphatasia patients with pyridoxine-responsive seizures in the literature, so early diagnosis of infantile hypophosphatasia in the clinically compatible patients allows more effective postnatal care/management and genetic counseling for further pregnancies.

20.Pseudotumour Cerebri Presentation in a Child Under the Gonadotropin-Releasing Hormone Agonist Treatment
Ülkü Gül, Ayşe Kaçar Bayram, Mustafa Kendirci, Nihal Hatipoğlu, Deniz Okdemir, Hakan Gümüş, Selim Kurtoğlu
doi: 10.4274/jcrpe.2212  Pages 365 - 367
Gonadotropin-releasing hormone analogues are common treatment option in central precocious puberty in childhood as well as in endometriosis, infertility, and prostate cancer in adults. Pseudotumor cerebri is a rare side effect observed in adults. We present the case of a girl with precocious puberty treated with triptorelin acetate who developed pseudotumor cerebri after the 4th dose. She had headaches, and her blood pressure was detected to be above the 99 percentile. There were no causes underlying of hypertension such as cardiac, renal, or endocrine. Neurological examination was normal except bilateral papilledema. Cranial magnetic resonance imaging was normal. Cerebrospinal fluid (CSF) opening pressure was elevated. Triptorelin therapy was ceased and acetazolamide was applied; CSF pressure returned to normal. We observed pseudotumor cerebri after precocious puberty treatment, a finding for the first time ever seen in childhood.

21.Attitudes of Pediatricians Regarding Prevention and Treatment of Vitamin D Deficiency
Gülcan Seymen Karabulut, Şükrü Hatun, Aysun X Aysun Bideci, Enver X Enver Hasanoğlu
doi: 10.4274/jcrpe.2978  Pages 368 - 371
To determine the adherence of pediatricians to the nationwide ‘Vitamin D Prophylaxis Program’ and to evaluate their attitudes about vitamin D intake. The study was conducted using the Turkish National Pediatrics Association network. The pediatricians were asked to respond to an online questionnaire that included five questions on ‘What dose of vitamin D they recommend for supplementation?’, ‘At what age they start vitamin D supplementation?’, ‘Supplementation method’, ‘Clichés and truths about vitamin D’, and ‘High-dose vitamin D therapy indications’. Responses of 167 pediatricians were evaluated in this study. 75.5% of pediatricians indicated that they recommended vitamin D supplementation in a daily dose of 400 IU. 47.1% started vitamin D supplementation by the end of the 2nd week. 7.83% of pediatricians suggested doubling the daily dose of vitamin D supplementation in infants with delayed tooth eruption, 19.9% suggested immediate cessation of vitamin D supplementation in infants with small anterior fontanels. This study showed that the majority of the pediatricians still prescribe vitamin D prophylaxis late, recommend high doses of vitamin D in cases of delayed tooth eruption, and think that low serum 25-hydroxy vitamin D level regardless of alkaline or phosphatase parathyroid hormone measurement is an indication for high-dose vitamin D (stoss) therapy. These results suggest a need for new training programs focusing on vitamin D supplementation.

22.Are Vitamin D Drops Containing 400 IU Daily Adequate for Preventing Vitamin D Deficiency?
Hüseyin Anıl Korkmaz
doi: 10.4274/jcrpe.3070  Page 372
Abstract |Full Text PDF

23.Crouzonodermoskeletal Syndrome with Hypoplasia of Corpus Callosum and Inferior Vermis
Fatih Gürbüz, Serdar Ceylaner, Ali Kemal Topaloğlu, Bilgin Yüksel
doi: 10.4274/jcrpe.3343  Pages 373 - 374
Abstract |Full Text PDF

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