Nesibe Andiran

Vitamin D Deficiency in Children and Adolescents

Objective Vitamin D deficiency is an important health problem in both developed and developing countries. Recent reports on the extraskeletal effects of vitamin D have led to increased interest in prevalence studies on states of deficiency/insufficiency of vitamin D. The aim of this study was to determine the frequency of vitamin D deficiency and insufficiency in children and adolescents residing in Ankara, Turkey and to investigate the factors associated with low vitamin D status. Methods: A total of 440 children and adolescents aged between 0 and 16 years were enrolled in this study. The subjects were divided into three groups according to their vitamin D status (deficiency ≤15 ng/mL; insufficiency: 15-20 ng/mL; sufficiency ≥20 ng/mL) and also according to their age (preschool<5 years; middle childhood: 5-10 years; adolescence: 11-16 years). Results: Overall, 40% of the subjects were found to have 25 hydroxy vitamin D [25(OH)D] levels of less than 20 ng/mL. The levels indicated a deficiency state in 110 subjects (25%) and insufficiency - in 66 (15%). The rate of vitamin D deficiency was higher in girls, regardless of age. 25(OH)D levels correlated negatively with age (r=-0.48, p<0.001), body mass index (BMI) (r=-0.20, p=0.001) and intact parathyroid hormone (iPTH) level (r=-0.31, p=0.001). A positive correlation was observed between 25(OH)D and serum ferritin levels (r=0.15, p=0.004). Conclusions: The high frequency of vitamin D deficiency in childhood (especially among adolescent girls) indicates a need for supplementation and nutritional support. Conflict of interest:None declared.

The evaluation of possible role of endocrine disruptors in central and peripheral precocious puberty

Abstract Exposure to environmental chemicals can affect genetic and epigenetic molecular pathways and may cause altered growth and development. Among those exposures, endocrine-disrupting chemicals (EDCs) are of particular concern as humans are abundantly exposed to these chemicals by various means in every period of life. Several well-known environmental chemicals, including phthalates and bisphenol A (BPA), are classified as EDCs. These EDCs are suggested to play roles in early onset of puberty in girls. The aim of this study is to determine plasma phthalate (di(2-ethylhexyl)phthalate [DEHP] and its main metabolite mono(2-ethylhexyl)phthalate [MEHP]) and urinary BPA levels in girls with idiopathic central precocious puberty (CPP) and peripheral precocious puberty (PPP). This study was performed on newly diagnosed idiopathic central precocious puberty (CPP) patients (n = 42) and peripheral precocious puberty (PPP) (n = 42) patients, who were admitted to Keçiören Training and Research Hospital, Clinic of Pediatric Endocrinology between August 2012 and –July 2013. Nonobese healthy girls (n = 50) were used as the control group. Urinary BPA levels were not statistically different in control, PPP and CPP groups (medians 10.91, 10.63 and 10.15 μg/g creatinine, respectively; p > 0.05). Plasma DEHP levels were significantly higher in PPP group when compared to control. Plasma MEHP levels were not significantly different in control and PPP groups (p > 0.05). However, in CPP group, both plasma DEHP and MEHP levels were significantly higher than control and PPP groups. This study showed that phthalates might play a role in the occurence of CPP in girls.

Incidence of maternal vitamin D deficiency in a region of Ankara, Turkey: a preliminary study.

BACKGROUND/AIM To evaluate vitamin D levels and risk factors for vitamin D deficiency in healthy newborns and their mothers. MATERIALS AND METHODS Ninety-nine healthy pregnant women (≥ 37 weeks of gestation) were enrolled in the study. Previous history of pregnancies and births, nutritional status, multivitamin supplementation, educational status, type of clothing, and the economic level of the family were recorded. Blood samples were drawn from the mothers and the umbilical cord of the newborns to measure serum 25(OH)D3, calcium, phosphorus, and parathormone levels. RESULTS While vitamin D insufficiency was identified as 62.6% in mothers, it was 58.6% in newborns; on the other hand, the incidence of vitamin D deficiency was 18.2% and 15.2% in mothers and newborns, respectively. Maternal serum 25(OH)D3 concentrations were not significantly related to the number of pregnancies or births, type of clothing, or the nutritional, economical, or educational status of the family (P > 0.05). CONCLUSION These findings suggest that despite a sunny environment, maternal vitamin D deficiency and insufficiency are still important health problems in a developed region of Turkey. Therefore, more effective vitamin D prophylaxis programs are required to prevent vitamin D deficiency in pregnant women and their offspring.

Ocular manifestations of Type 1 diabetes mellitus in pediatric population

Context: To evaluate the necessity of ocular screening in Type 1 diabetes mellitus (DM). Aims: This study aims to investigate the diabetes-related ocular changes according to the glycosylated hemoglobin (HbA1c) level and duration of diabetes in children and compare the results with nondiabetic healthy children. Settings and Design: Observational cross-sectional study designed by ophthalmology and pediatric endocrinology clinics. Subjects and Methods: Forty-two children with Type 1 DM, 42 healthy gender- and age-matched children as controls were enrolled. All patients underwent ophthalmic and physical examination, with a review of medical history and current medication. HbA1c level, best corrected visual acuity, intraocular pressure (IOP), central corneal thickness (CCT), tear break-up time (BUT), Schirmer test, dilated fundus examination findings, central retinal thickness (CRT), and total macular volume (TMV) measurements were noted. Statistical Analysis: Descriptive statistics, Students t-test, Mann–Whitney U-test, Chi-square test for comparison of the group parameters and correlation analyses (Spearman analysis) were performed with SPSS statistical software 17.0 (SPSS Inc., Chicago, IL, USA). Results: Type 1 DM group exhibited significantly reduced Schirmer test, increased IOP and decreased retinal thickness relative to the age-matched control group (P < 0.05) but no statistically significant difference was found for the BUT (P = 0.182) and for the CCT (P = 0.495). The correlations between the age, duration, HbA1c and IOP, BUT, Schirmer test, TMV, CRT measurements did not reach statistical significance. Conclusions: More frequent screening may be needed for complications, including neuropathy-related dry eye syndrome, IOP changes, and diabetic retinopathy in children with Type 1 DM.

Turner syndrome and associated problems in turkish children: A multicenter study

Objective: Turner syndrome (TS) is a chromosomal disorder caused by complete or partial X chromosome monosomy that manifests various clinical features depending on the karyotype and on the genetic background of affected girls. This study aimed to systematically investigate the key clinical features of TS in relationship to karyotype in a large pediatric Turkish patient population. Methods: Our retrospective study included 842 karyotype-proven TS patients aged 0-18 years who were evaluated in 35 different centers in Turkey in the years 2013-2014. Results: The most common karyotype was 45,X (50.7%), followed by 45,X/46,XX (10.8%), 46,X,i(Xq) (10.1%) and 45,X/46,X,i(Xq) (9.5%). Mean age at diagnosis was 10.2±4.4 years. The most common presenting complaints were short stature and delayed puberty. Among patients diagnosed before age one year, the ratio of karyotype 45,X was significantly higher than that of other karyotype groups. Cardiac defects (bicuspid aortic valve, coarctation of the aorta and aortic stenosis) were the most common congenital anomalies, occurring in 25% of the TS cases. This was followed by urinary system anomalies (horseshoe kidney, double collector duct system and renal rotation) detected in 16.3%. Hashimoto’s thyroiditis was found in 11.1% of patients, gastrointestinal abnormalities in 8.9%, ear nose and throat problems in 22.6%, dermatologic problems in 21.8% and osteoporosis in 15.3%. Learning difficulties and/or psychosocial problems were encountered in 39.1%. Insulin resistance and impaired fasting glucose were detected in 3.4% and 2.2%, respectively. Dyslipidemia prevalence was 11.4%. Conclusion: This comprehensive study systematically evaluated the largest group of karyotype-proven TS girls to date. The karyotype distribution, congenital anomaly and comorbidity profile closely parallel that from other countries and support the need for close medical surveillance of these complex patients throughout their lifespan.

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.

Hypophosphatemic rickets caused by a novel splice donor site mutation and activation of two cryptic splice donor sites in the PHEX gene

Abstract X-linked hypophosphatemic rickets (XLH) is the most common inherited form of rickets. XLH is caused by inactivating mutations in the PHEX gene and is transmitted as an X-linked dominant disorder. We investigated PHEX mutation in a sporadic Turkish girl with hypophosphatemic rickets. The patient was 2 years of age with a complaint of inability to walk. She had bowing of legs and growth retardation. Laboratory data showed normal calcium, low phosphate with markedly elevated ALP, and low phosphate renal tubular reabsorption. She was treated with Calcitriol 0.5 mg/kg/day and oral phosphate supplement with good response. The entire coding region of PHEX gene was sequenced from patient’s peripheral leukocyte DNA and a novel 13 bp deletion at the donor splice site of exon5 was found (c.663+12del). Instead of using the donor splice site of intron 4 to splice out exon 5 and intron 5, the spliceosome utilized two nearby cryptic donor splice sites (5′ splice site) to splice out intron 4, resulting in two smaller transcripts. Both of them could not translate into functional proteins due to frameshift. Her parents did not carry the mutation, indicating that this is a de novo PHEX mutation likely resulting from mutagenesis of X chromosome in paternal germ cells. We conclude that c.663+12del is a novel mutation that can activate nearby cryptic 5′ splice sites. The selection of cryptic 5′ splice sites adds the complexity of cell’s splicing mechanisms. The current study extends the database of PHEX mutation and cryptic 5′ splice sites.

Growth curves for Turkish Girls with Turner Syndrome: Results of the Turkish Turner Syndrome Study Group.

Objective: Children with Turner syndrome (TS) have a specific growth pattern that is quite different from that of healthy children. Many countries have population-specific growth charts for TS. Considering national and ethnic differences, we undertook this multicenter collaborative study to construct growth charts and reference values for height, weight and body mass index (BMI) from 3 years of age to adulthood for spontaneous growth of Turkish girls with TS. Methods: Cross-sectional height and weight data of 842 patients with TS, younger than 18 years of age and before starting any therapy, were evaluated. Results: The data were processed to calculate the 3rd, 10th, 25th, 50th, 75th, 90th and 97th percentile values for defined ages and to construct growth curves for height-for-age, weight-for-age and BMI-for-age of girls with TS. The growth pattern of TS girls in this series resembled the growth pattern of TS girls in other reports, but there were differences in height between our series and the others. Conclusion: This study provides disease-specific growth charts for Turkish girls with TS. These disease-specific national growth charts will serve to improve the evaluation of growth and its management with growth-promoting therapeutic agents in TS patients.

Cushing’s syndrome: hidden risk in usage of topical corticosteroids

Abstract Iatrogenic Cushing’s syndrome in children may occur as a result of the application of exogenous steroids. Prolonged use of powerful corticosteroids suppresses adrenal functions and iatrogenic Cushing’s syndrome may develop particularly in infants who are given topical corticosteroids. We report here a case on three infants having Cushing’s syndrome with similar clinical presentations due to overuse of topical steroids for diaper dermatitis. The importance of exercising caution during the use of topical steroids is underlined in this study.

Accelerated idioventricular rhythm associated with propranolol treatment in a child.

Accelerated idioventricular rhythm (AIVR) is a ventricular arrhythmia most commonly seen in adults with underlying cardiac disease. It is important to establish the diagnosis when it occurs to differentiate this benign phenomenon from dangerous ventricular tachycardia. We present the case of a healthy child who developed episodes of AIVR associated with propranolol treatment. Her 24-hour electrocardiography recording showed AIVR with difference between sinus and ventricular beats. The arrhythmia resolved with the discontinuation of propranolol, and eventually the case was in sinus rhythm. This patient is the first case of AIVR associated with propranolol treatment in the literature.