Band 28, Heft 11-12

Objective: We analyzed mRNA expression of X-linked inhibitor of apoptosis protein (XIAP) in patients with Turner syndrome (TS) and examined its association with phenotypic features. Subjects and methods: XIAP mRNA expression levels were investigated in 98 patients with TS in total RNA extracted from blood leucocytes by real time quantitative polymerase chain reaction. Results: Levels of XIAP mRNA were significantly lower in patients with bicuspid aortic valves (BAV; n=13) than those without (log XIAP –1.17±0.3 vs. –0.94±0.2, p=0.002). Significantly higher expression of XIAP mRNA was seen in patients with a mosaic karyotype and renal malformations (log XIAP –0.79±0.3 vs. –1.0±0.3, p=0.03). No correlations were seen between XIAP and other manifestations. Conclusion: Abnormal expression of XIAP may be an important underlying mechanism in the development of BAV and renal malformations in TS. However, abnormal XIAP mRNA expression, as determined from peripheral mononuclear cells, does not appear to explain all the somatic and visceral stigmata of TS.

Objective: Primary gonadal failure may occur in most individuals with Turner syndrome (TS). Since ovaries in TS girls undergo premature apoptosis and cryopreservation of ovarian tissue is now feasible, it would be useful to identify a reliable marker of ovarian reserve in these patients. We planned to evaluate ovarian function in a group of TS patients by measuring both traditional markers and inhibin B and to compare these results with those of a control group. Study design: We enrolled 23 patients with TS and 17 age-matched healthy girls. The median age of our TS patients was 17.6 years. Three out of the 23 patients (13%) showed spontaneous pubertal development and regular menstrual cycles; the remaining 20 (86.9%) presented with primary amenorrhea. Results: The median level of inhibin B in the TS patients with primary amenorrhea was 42 pg/mL and did not differ significantly among the different subgroups in relation to karyotype. The median inhibin B level in the control group was significantly higher than in the TS girls with primary amenorrhea (83 vs. 42 pg/mL, p<0.00001). In the three patients with TS and spontaneous menstrual cycles, the inhibin B levels were significantly higher when compared to the values of the TS girls with primary amenorrhea. Conclusion: TS patients with primary amenorrhea have significantly lower levels of inhibin B than TS girls with spontaneous puberty and healthy controls. Inhibin B does not correlate with follicle-stimulating hormone/luteinizing hormone. If our results are confirmed in further studies, inhibin B could become a first-line screening test for assessing ovarian reserve and a longitudinal marker of the possible decline of ovarian function in TS.

Background: Age at diagnosis of girls with Turner syndrome (TS) is an important indicator of successful management. We determined the age, initial clinical presentation, and chromosomal abnormalities in patients with TS. Methods: This was a retrospective evaluation of the clinical and laboratory records of patients with TS. Results: Sixty-five patients with TS were identified; 40 (62%) were diagnosed after age 5 years. The main presenting features were short stature, delayed puberty, dysmorphic features, and neonatal lymphoedema. Chromosomal analysis of this cohort showed that 31 patients demonstrated mosaicism, while a 45,X karyotype was observed in 19. The remaining patients had variable abnormalities including deletion, translocation, isochromosome, and ring chromosome. Y-chromosome material was found in four cases. Conclusions: Most patients with TS were diagnosed after age 5 years, had a varied clinical presentation, and had a wide range of chromosomal abnormalities.

Objective: The objective of the study was to evaluate the pubertal development and linear growth of Turner Syndrome (TS) girls regularly monitored in our department. Patients and methods: The data of 13 patients with TS were evaluated retrospectively. Left hand radiograms were evaluated by three different pediatric endocrinologists to determine bone ages. Results: Six (46.2%) of the TS girls were treated with oral estrogens, while 7 (53.8%) were treated with transdermal estrogen. The ratios of chronological age (CA) difference to bone age (BA) difference (ΔCA/ΔBA) in two groups of patients treated with estrogen were compared at the time of the last control. The ΔCA/ΔBA ratio in the transdermal estrogen-treated group was significantly higher (p=0.005). These results suggest slower BA progression in the TS girls treated with transdermal estrogen. Conclusion: BA advancement is less significant with transdermal estrogen, which is associated with adequate breast development.

The aim of this study was the evaluation of Turner syndrome inside the Albanian population, its clinical, cytological and genetic characteristics, the accompanying pathologies, and the efficacy of the treatment with the growth hormone. We performed a retrospective analysis of 59 patients suffering from this syndrome (aging from 5 to 23 years old). The diagnosis of female patients suffering from Turner syndrome is delayed, with a mean age at the moment of diagnosis of 13.74 years (5–23 years). The main reason for seeking medical advice was the growth retardation or a delayed puberty. Available data for 52 patients showed that the most frequent accompanying pathologies were the following: thyroid autoimmune disorders (59%), cardiovascular anomalies (43%), renal pathologies (41%), hearing impairment (4.3%) and hypertension (3.3%). Follow-up for the growth rate was possible for 52 patients out of the total of 59 patients. Twenty-five of the female patients suffering Turner syndrome and forming part of our study sample were treated with growth hormone for a period averaging 3 years and 4 months. A variety of reasons was identified as responsible for the missed treatment in 27 patients. We saw an enhanced growth (in terms of body height) within the treated subgroup, when compared with the untreated subgroup (27 patients), especially during the first 3 years of the follow-up. No side effects of this treatment were reported. Both groups of patients initiated as well a sexual hormone therapy (estrogens and progesterone) for inducing puberty at the age of 12 years. Further work is needed for an early diagnosis of this syndrome, the prompt treatment with growth hormone and the monitoring of accompanying disorders. This will ensure a better quality of life and an improvement of the longevity of patients suffering from the Turner syndrome.

Among children and adolescents, metabolic syndrome (MetS) is more common than previously believed. Hence, any information on the relation between vitamin D insufficiency/deficiency and insulin resistance (IR) in this population with risk of developing MetS is of great importance. This review analyzes and evaluates the existing evidence from cross-sectional, observational, and retrospective studies concerning the effect of vitamin D insufficiency/deficiency on MetS as a whole or on its various components. Most data show that insufficient vitamin D status is associated with increased prevalence of MetS or its individual components, mainly blood pressure and IR, often independent of overall obesity or abdominal adiposity. The implications of these findings could be associated with increased risk for developing cardiovascular disease and type 2 diabetes mellitus in later life. The very few randomized control trials examining any possible beneficial effects of vitamin D supplementation are also included.

Cryptorchidism is one of the most common birth defects in male children, and it has a potential impact on future health. It is the best-characterized risk factor for reduced fertility and testicular cancer. However, the etiology of cryptorchidism remains largely unknown. In the literature, we find different opinions and theories on this topic. Probably, the etiology is multifactorial, and hormonal, genetic and environmental factors may regulate testicular development and descent from intra-abdominal location into the bottom of the scrotum. The descent of the testis is a complex, two-stage process. A critical role in testicular descent has been attributed to androgens, insulin-like hormone 3 (insl3) and anti-Müllerian hormone. It is believed that interaction between Leydig and Sertoli cells may cause impaired spermatogenesis. Based on recent knowledge of germ cell development, it is believed that the best treatment for undescended testis is orchiopexy between 6th and 12th month of life. Long follow-up studies are needed to focus on the effect of this recommendation.

Aim: Androgen receptor ( AR ) gene mutations are the leading cause of 46,XY disorders of sex development (DSD) and are associated with varying degrees of androgen insensitivity. The aim of this study is to investigate AR gene mutations in 46,XY DSD patients with normal testosterone secretion, either normal or high testosterone/dihydrotestosterone (T/DHT) ratio and normal SRD5A2 gene analysis, collectively, suggestive of androgen insensitivity syndrome (AIS). Methods: We direct sequenced all eight exons of the AR gene in 21 index patients with varying degrees of undervirilization. Results: We detected AR gene alterations in five patients. In patients with complete AIS we found p.Val30Met in exon 1 and p.Gly689* in exon 4. One patient with partial AIS had p.Gln712Glu in exon 4. In two patients with partial phenotype, we found common p.Glu213Glu (c.639G>A) SNP, and an additional p.Ile817Ile (c.2451T>C) mutation was found in one of these two patients. Discussion: Despite the fact that T/DHT ratio is frequently used in diagnosis of AIS, lack of precisely determined cutoffs compromises correct diagnosis. Hence, depending on clinical and biochemical findings solely may delay correct diagnosis. Direct sequence analysis of the AR is essential for precise diagnosis of AIS.

Aim: To perform molecular analysis of pediatric maturity onset diabetes of the young (MODY) patients by next-generation sequencing, which enables simultaneous analysis of multiple genes in a single test, to determine the genetic etiology of a group of Turkish children clinically diagnosed as MODY, and to assess genotype-phenotype relationship. Methods: Forty-two children diagnosed with MODY and their parents were enrolled in the study. Clinical and laboratory characteristics of the patients at the time of diagnosis were obtained from hospital records. Molecular analyses of GCK , HNF1A , HNF4A , HNF1B , PDX1 , NEUROD1 , KLF11 , CEL , PAX4 , INS , and BLK genes were performed on genomic DNA by using next-generation sequencing. Pathogenicity for novel mutations was assessed by bioinformatics prediction software programs and segregation analyses. Results: A mutation in MODY genes was identified in 12 (29%) of the cases. GCK mutations were detected in eight cases, and HNF1B , HNF1A , PDX1 , and BLK mutations in the others. We identified five novel missense mutations – three in GCK (p.Val338Met, p.Cys252Ser, and p.Val86Ala), one in HNF1A (p.Cys241Ter), and one in PDX1 (p.Gly55Asp), which we believe to be pathogenic. Conclusion: The results of this study showed that mutations in the GCK gene are the leading cause of MODY in our population. Moreover, genetic diagnosis could be made in 29% of Turkish patients, and five novel mutations were identified.

Background: Children with type 1 diabetes mellitus (T1DM) have low physical activity levels and are at high risk for psychosocial morbidities, including depression, heightened anxiety and low health-related quality of life (HRQoL). Objective: The aim of this study was to assess the associations of physical activity level with depression, anxiety, and HRQoL in children with T1DM. Subjects and methods: A cross-sectional study design, including children with T1DM aged between 8 and 12 years and healthy controls, was used. Physical activity (PA) level was assessed with the Physical Activity Questionnaire for Older Children (PAQ-C). Anxiety was screened by The Screen for Anxiety Related Emotional Disorders (SCARED) questionnaire. Depressive symptoms were evaluated using the Children’s Depression Inventory (CDI). Quality of life was assessed with the The Pediatric Quality of Life Inventory 4.0 (PedsQL 4.0). Results: Forty-seven T1DM and 55 healthy children were included with mean ages of 9.87±1.63 and 9.56±1.60 years, respectively. The T1DM group had significantly higher depression and anxiety score (p<0.05) and lower HRQoL-child self-report score (p<0.05, for all) compared with the control group. Significant associations were found between PAQ-C and PedsQL 4.0 (p<0.05), between SCARED and PedsQL 4.0 (p<0.05), and between HbA1c and PedsQL 4.0 (p<0.05) in children with T1DM. Conclusions: The result of our study suggested that only HRQoL was related to physical activity, anxiety and HbA1c in children with T1DM.

Background: Neonatal diabetes has not been previously studied in Ukraine. We investigated the genetic etiology in patients with onset of diabetes during the first 9 months of life. Methods: We established a Pediatric Diabetes Register to identify patients diagnosed with diabetes before 9 months of age. Genetic testing was undertaken for 42 patients with permanent or transient diabetes diagnosed within the first 6 months of life (n=22) or permanent diabetes diagnosed between 6 and 9 months (n=20). Results: We determined the genetic etiology in 23 of 42 (55%) patients; 86% of the patients diagnosed before 6 months and 20% diagnosed between 6 and 9 months. The incidence of neonatal diabetes in Ukraine was calculated to be 1 in 126,397 live births. Conclusions: Genetic testing for patients identified through the Ukrainian Pediatric Diabetes Register identified KCNJ11 and ABCC8 mutations as the most common cause (52%) of neonatal diabetes. Transfer to sulfonylureas improved glycemic control in all 11 patients.

Background: The incidence of postoperative nausea and vomiting (PONV) can be reduced by dexamethasone. Single-dose administration may cause elevated blood glucose levels in obese adults. No data are available for children. Objective: The aim was to evaluate perioperative blood glucose changes related to body weight in children who received dexamethasone. Patients and methods: This prospective observational study included 62 children. All patients received total intravenous anesthesia and a single dose of dexamethasone (0.15 mg/kg, maximum 8 mg). Blood glucose levels were measured up to 6 h. Standard deviation scores (SDS) were calculated using age- and gender-specific body mass index (BMI) percentiles, p<0.05. Results: A total of 62 children (11.5±2.9 years, median SDS 0.43, 29% overweight/obese) were included. Blood glucose levels increased from 5.52±0.52 to 6.74±0.84 mmol/L 6 h after dexamethasone without correlation to the BMI-SDS. Conclusions: This study showed an increase of perioperative blood glucose (normoglycemic ranges) after single dose of dexamethasone, but no BMI-dependent effect was observed in children. Therefore, low-dose dexamethasone may be used in obese children for PONV prophylaxis.

Studies performed on mice suggest that adropin is a peptide hormone playing a role in metabolic homeostasis and prevention of obesity-associated insulin resistance. Our study was conducted to investigate the role of adropin in children with obesity or metabolic syndrome. The study group consisted of 70 patients, including 42 obese and 28 with metabolic syndrome, and 26 healthy volunteers. After anthropometric variables and blood pressure of all participants were measured, serum lipids were analyzed, liver USG and oral glucose tolerance test were performed, and HOMA-IR values were calculated. Plasma adropin levels were collectively analyzed from collected plasma samples. In patient and control groups, no difference was observed in the levels of adropin (327.7±124.7 vs. 344.6±208.5 ng/L, respectively). The adropin levels of metabolic syndrome, obesity, and control groups also showed no difference (316±142.3, 335.8±112.5, and 344.6±208.5 ng/L, respectively). While the adropin levels of patients with and without hepatic steatosis were 319.6±123.7 and 347.8±128.7 ng/L, respectively, patients with HOMA-IR values of <3.16 and ≥3.16 had levels 342.3±124.8 and 296.5±136.7 ng/L, respectively. Although statistically insignificant, our findings are considered to support the hypothesis suggesting a nexus between adropin and obesity and metabolic syndrome. Small sample size in our study may have prevented our results to reach a more significant level. So, long-term follow-up studies with large population are needed to enlighten the role of adropin in metabolic homeostasis.

Background: Carnitine is necessary for the transfer of long-chain fatty acids from the cytosol into mitochondria for subsequent β-oxidation. A carnitine deficiency results in impaired energy production from fatty acids. Methods: We reviewed the plasma level of total carnitine, free carnitine, and acylcarnitines in 1270 children with psychomotor retardation, low growth, and weight parameters. Tandem mass spectrometry (MS/MS) was applied. Low free carnitine level in plasma was used as a marker of carnitine deficiency. Results: A total of 102 (8%) children had free carnitine level <19 μmol/L (norm 19–60 μmol/L). As a result of the subsequent investigation, hereditary diseases were diagnosed in 76 (¾) children and out of that 19 had very low free carnitine plasma level (<10 μmol/L). Fanconi syndrome, fat oxidation defects, primary systemic carnitine deficiency, mitochondrial encephalomyopathy, and Noonan syndrome were revealed in these 19 children. Conclusion: Efficacy of levocarnitine treatment in children with very low free carnitine level differs according to pathogenesis of diseases. The highest efficacy was observed in primary systemic carnitine deficiency.

Craniopharyngioma is a histologically benign brain malformation with a fundamental role in satiety modulation, causing obesity in up to 52% of patients. Aim: To evaluate cardiovascular risk factors, body composition, resting energy expenditure (REE), and energy intake in craniopharyngioma patients and to compare the data with those from children with multifactorial obesity. Population: All obese children and adolescents who underwent craniopharyngioma resection and a control group of children with multifactorial obesity in follow-up between May 2012 and April 2013. Materials and methods: Anthropometric measurements, bioelectrical impedance, indirect calorimetry, energy intake, homeostatic model assessment insulin resistance (HOMA-IR), and dyslipidemia were evaluated. Results: Twenty-three patients with craniopharyngioma and 43 controls were included. Children with craniopharyngioma-related obesity had a lower fat-free mass percentage (62.4 vs. 67.5; p=0.01) and a higher fat mass percentage (37.5 vs. 32.5; p=0.01) compared to those with multifactorial obesity. A positive association was found between %REE and %fat-free mass in subjects with multifactorial obesity (68±1% in normal REE vs. 62.6±1% in low REE; p=0.04), but not in craniopharyngioma patients (62±2.7 in normal REE vs. 61.2±1.8% in low REE; p=0.8). No differences were found in metabolic involvement or energy intake. Conclusions: REE was lower in craniopharyngioma patients compared to children with multifactorial obesity regardless of the amount of fat-free mass, suggesting that other factors may be responsible for the lower REE.

We investigated whether there is a relationship between serum cholesterol and bone mineral density (BMD), independent of BMI in children and adolescents. This study was based on data from the KNHANES 2009–2010. The data for 1557 children and adolescents were analyzed and classified into three groups: underweight, normal-weight, and overweight. We analyzed the relationships between serum cholesterol and BMD z-scores. Whole body BMD z-score was revealed as an inverse association with the serum cholesterol quartile in only normal-weight group (p=0.008). Serum cholesterol level correlated more inversely with BMD z-score in normal-weight boys ( r 2 =0.040, p=0.002) than in girls ( r 2 =0.019, p=0.042). Multivariate regression analysis identified serum cholesterol as association with BMD in normal-weight ( r 2 =0.020, p=0.002). Serum cholesterol concentration may be a detrimental risk factor for BMD in normal-weight children and adolescents independent of BMI.

Aim: To investigate whether there is a change in bone turnover-related biochemical markers and bone mineral density of children with constitutional delay of growth and puberty (CDGP) in the prepubertal period. Methods: We measured serum calcium, phosphorus, alkaline phosphatase, parathormone, 25-OH vitamin D, osteocalcin, osteoprotogerin and urinary deoxypyridinoline levels (D-pyd), and bone mineral density (BMD) in 31 prepubertal boys with CDGP. These children were compared with 22 prepubertal boys with familial short stature (FSS) and 27 normal prepubertal boys. Results: Urinary D-pyd was significantly high in CDGP group as compared to control group (p=0.010). Volumetric BMD did not significantly differ between CDGP, FSS, and control groups (p=0.450). Volumetric BMD and urinary D-pyd levels of FSS and control groups were similar. Mean or median levels of calcium, phosphorus, alkaline phosphatase, parathormone, and osteoprotegerin did not significantly differ between CDGP, FSS, and control groups. Conclusions: Our data suggest that prepubertal boys with CDPG have normal bone turnover. However, their significantly higher urinary D-pyd levels relative to those of FSS and control groups might be an indicator of later development of osteoporosis. Therefore, long-term follow-up studies monitoring bone mineral status of prepubertal boys with CDPG from prepuberty to adulthood are needed to better understand bone metabolism of these patients.

Purpose: The objective of the study was to determine the incidence of vitamin B 12 deficiency in patients under long-term treatment for phenylketonuria (PKU) and hyperphenylalaninemia (HPA), as well as its associations with B 12 vitamin parameters (holotranscobalamin – active vitamin B 12 , serum folate, total plasma homocysteine, and plasma methylmalonic acid concentration). Patients and methods: The group consisted of 51 PKU (n=29) and HPA (n=22) patients aged 3–48 years (28 children, 23 adults). Results: A significant difference in serum folate levels was discovered between adult HPA patients and PKU patients (p=0.004, Mann-Whitney U-test). A significant difference in plasma homocysteine concentrations within the normal levels (p=0.032, χ 2 -test) was detected between adult HPA and PKU patients. In the group of adults, we also found significant differences in serum holotranscobalamin concentrations regarding both concentration levels and the proportion of patients with concentrations within the normal levels (p=0.031, Mann-Whitney U-test; p=0.006, χ 2 -test). Conclusion: We have proven that adult patients with PKU and HPA are at risk of vitamin B 12 nutritional deficiency. The most effective parameter for these adults is the monitoring of holotranscobalamin in the serum.

The aim of the present study was to analyse the effects of combined treatment with calcitriol and phosphate, to find out the incidence of the nephrocalcinosis, and to elucidate the risk factor of nephrocalcinosis in patients with hypophosphatemic rickets. We followed six patients. The median age at diagnosis was 3.25 (0.75–10.5) years. The median follow-up duration was 8.25 (3.5–12.5) years. The mean dose of calcitriol and phosphate treatments was 39.1±8 ng/kg/day, 90.5±57.1 mg/kg/day, respectively. Nephrocalcinosis was detected in three patients (50%). The mean dose of phosphate taken by the patients found to have nephrocalcinosis was detected to be high with a statistically significant difference (p=0.041). No significant relationship was found the mean dose of calcitriol. We found no relationship between the development of nephrocalcinosis and the incidence of hypercalciuria or hypercalcemia episodes. We found the increased phosphate dose administered for treatment to play a role in nephrocalcinosis development.

Background: Hyperthyroidism is much less common in children <7 years vs. older children and less well studied. It was our impression that the youngest patients needed a higher weight-based dose of methimazole (MMI) to achieve euthyroidism. Objectives: To compare the mean MMI dose needed to normalize free T4 in younger (<7 years) vs. older children and the time taken to normalize free T4. Methods: Based on chart review (2004–2012), patients were divided into groups based on age at diagnosis: <7 years (n=13), 7–12 years (n=30) and >12 years (n=40). Follow-up visits were reviewed until free T4 normalized. Results: The mean dose of MMI (mg/kg/day) needed to normalize free T4 was 0.71 (±0.29) in the <7 group, significantly higher vs. the two older groups: 0.50 (±0.22) and 0.44 (±0.24). Months taken to achieve a euthyroid state was significantly longer in children <7 (6.23±3.91) vs. the older groups (3.10±2.12 and 3.18±2.86 months). Conclusion: Hyperthyroid children diagnosed before age 7 required higher initial doses of MMI and took a longer time to become euthyroid than older patients. Clinicians should consider starting with higher weight-based MMI doses when treating younger patients to more rapidly normalize free T4.

Background: In childhood and adolescence, some patients with cerebral palsy (CP) have long-term limited mobility, which can lead to secondary osteoporosis, Prevention and treatment strategies have been evaluated for the management of low bone mineral density (BMD) and fragility fractures. Currently, however, there are no established guidelines for the stratification and individualization of therapeutic interventions. Recently, an increasing number of studies have reported on the use of bisphosphonates to increase BMD in various pediatric conditions, and bisphosphonates have been suggested as a method to treat osteoporosis and prevent fractures. Purpose: We performed the current meta-analysis to assess the effects of bisphosphonates on increasing BMD in children who have CP with secondary osteoporosis. Materials and methods: A search of PubMed, Cochrane, and Embase from inception to April 2014 was performed with the following keywords: (bone disease, metabolic OR osteoporosis OR osteopenia) AND (child OR pediatric OR adolescent) AND (cerebral palsy) AND (bisphosphonate). Four studies were ultimately included in the meta-analysis: one randomized, double-blinded, placebo-controlled study and three case-controlled studies. Results: The Z-score of lumbar spine was significantly improved after bisphosphonates treatment compared with pre-treatment values (standardized mean difference [SMD], 0.799; 95% confidence interval [CI], 0.499–1.100; p<0.001). The Z-score of femur was also improved significantly compared with that of the baseline value (SMD, 0.748; 95% CI, 0.382–1.114; p<0.001). Conclusions: Bisphosphonates have a significant effect on improving BMD in children with CP. Further standardization of treatment protocols including treatment dosage and duration needs to be established, and long-term follow up studies are needed.

Background: The possible difference of antimüllerian hormone (AMH) levels at central precocious puberty (CPP) and premature thelarche (PT) has not been properly evaluated. Objective/hypothesis: By evaluating AMH levels in girls with diagnosed CPP and PT, we aim to show the change of AMH levels at the pubertal onset. Subjects: Sixty-five girls who have breast development before the age of 8 years and 25 healthy girls were enrolled in the study. Methods: The subjects were divided into two groups as CPP and PT, according to results of GnRH test. AMH levels were determined in the two groups. Results: The mean AMH levels of the CPP group were significantly lower than those in the PT group (13.57±9.85 pmol/L and 58.42±12.78 pmol/L, respectively, p=0.022). Conclusion: These results suggest that the AMH levels decrease in the duration of the hypothalamus-pituitary-ovarian axis activation. We thought that AMH might/may be a marker for distinguishing between CPP and PT.

Background: Taking multiple anthropometric measurements for the description of body proportions in an accurate way is a time-consuming procedure that requires specific tools and skills. This is why we developed an alternative method based on digital photography for taking these measurements which is faster and easier to use, to make anthropometry more user-friendly and approachable to paediatricians. Methods: We conducted a cross-sectional study in 54 children between 2 and 18 years of age. We compared manual measurements with photogrammetric measurements to validate our method. Results: Inter-observer correlations of all measurements are ≥0.96 and mean differences are 0.3–0.9 cm, except for arm span. Comparison of manual to photogrammetric measurements shows mean differences of 0.6–1.3 cm, with correlations ≥0.92, except for sitting height and arm span. Correlations of ratios between methods are height/sitting height ( r= 0.77), biacromium/biiliacum ( r =0.74) and subischial leg length/sitting height ( r =0.75) . Conclusion: Photogrammetric anthropometry is faster, easier to use and provides the paediatrician with more flexibility as taking the digital photographs and performing the analysis are separated.

Objective: Little has been published on treatment of precocious puberty in girls with Williams-Beuren syndrome (WBS), a condition occurring frequently in this group. We analyzed our own data on growth/age at menarche of now adult female patients with WBS being diagnosed with central precocious puberty or early puberty. Data of patients treated with gonadotropin-releasing hormone (GnRH) analog (n=13) were compared with those not treated (control group, n=11). Patients: Longitudinal data on the somatic development of 24 now adult female patients were analyzed. Results: Medium final height was 157.2±6.5 cm compared to 151.4±5.6 cm in the control group. No significant difference could be found in the discrepancy of genetic target height and final height. Prepubertally girls were normal weight in both groups; in adulthood the majority of patients were overweight/obese. Menarche commenced 11 months after cessation of therapy. Conclusion: As already known from other studies, hormonal suppression via GnRH analog was well tolerated.

Puberty is regulated by the endocrine system, which when disrupted can affect reproductive health. Endocrine disrupters (ED) are involved in the pathogenesis of idiopathic central precocious puberty (ICPP). Polybrominated diphenyl ethers (PBDE) are lipophilic, persistent ED used as flame retardants in several products; thus, human population is exposed through food and domestic dust. PBDE exposure during the peripubertal period is suspected to interfere with reproductive development. The study aimed to investigate PBDE serum concentration in 31 girls with ICPP as well as describe their dietary habits and lifestyles. The PBDE median level was 59 ng/g of lipids, higher than in healthy girls in comparable studies. Interestingly, elder girls and girls with higher body mass index (BMI) showed higher PBDE serum levels. Considering the relevance of altered puberty onset as a risk factor for reproductive health, studies on food contribution to PBDE exposure in Italian children, and efforts to ameliorate risk assessment for emerging chemicals are suggested.

Background: Although most hypocalcemia with hypomagenesemia in the neonatal period is due to transient neonatal hypoparathyroidism, magnesium channel defects should also be considered. Case: We report a case of persistent hypomagnesemia in an 8-day-old Hispanic male who presented with generalized seizures. He was initially found to have hypomagnesemia, hypocalcemia, hyperphosphatemia and normal parathyroid hormone. Serum calcium normalized with administration of calcitriol and calcium carbonate. Serum magnesium improved with oral magnesium sulfate. However, 1 week after magnesium was discontinued, serum magnesium declined to 0.5 mg/dL. Magnesium supplementation was immediately restarted, and periodic seizure activity resolved after serum magnesium concentration was maintained above 0.9 mg/dL. The child was eventually weaned off oral calcium and calcitriol with persistent normocalemia. However, supraphysiologic oral magnesium doses were necessary to prevent seizures and maintain serum magnesium at the low limit of normal. Methods and results: As his clinical presentation suggested primary renal magnesium wastage, TRPM6 gene mutations were suspected; subsequent genetic testing revealed the child to be compound heterozygous for TRPM6 mutations. Conclusion: Two novel TRPM6 mutations are described with a new geographic and ethnic origin. This case highlights the importance of recognizing disorders of magnesium imbalance and describing new genetic mutations.

Background: Persistent Mullerian duct syndrome (PMDS) is a rare form of male 46,XY disorder of sex development characterized by the presence of Mullerian duct derivatives in otherwise phenotypically normal males. Aim : To report a novel mutation of the anti-Mullerian hormone ( AMH ) gene in two of three siblings with PMDS. Cases: A 2-year-old male presented with recurrent left-sided inguinal hernia and absence of right testis. Laparoscopic surgery disclosed Mullerian duct derivates and transverse testicular ectopia. AMH level was found to be low [1.6 ng/mL (normal range 7.4–373.1), 11.42 pmol/L (normal range 52.8–2663.9)]. His 15-year-old and 7-year-old elder brothers were invited, and bilateral undescended testes were noted upon examination. Female reproductive structures were identified during surgery but no transverse testicular ectopia. All cases had 46,XY karyotype. Genetic analyses could be done in two of them and a unique homozygous T to C base substitution was found at position 1591 in the AMH gene. Conclusion: This is the first report of the AMH gene mutation which is referred as p.Y531H (c.1591T>C), which resulted in different phenotypes of PMDS in three siblings.

Association of Kocher-Debré-Semelaigne syndrome–a myopathy of hypothyroidism in childhood characterized by muscular hypertrophy, with rhabdomyolysis is very rare. We present a case of Kocher-Debré-Semelaigne syndrome with rhabdomyolysis secondary to Hashimoto’s thyroiditis. He had muscular symptoms simulating poly/dermatomyositis, massively elevated creatine kinase (CK) levels and high creatinine levels. All of the findings reversed on treatment of hypothyroidism. The response to the therapy strongly suggested that Kocher-Debré-Semelaigne (KDS) syndrome was the underlying etiology. Serum thyroid- stimulating hormone levels should be routinely determined in all patients with muscular symptoms and/or elevation of CK and creatinine, keeping KDS syndrome in mind.

Gonadotropin-releasing hormone analogues are generally regarded as safe drugs. Gonadorelin acetate has been widely used for the diagnosis of central precocious puberty, and life-threatening reactions to gonadorelin acetate are extremely rare. Herein, we described – to the best of our knowledge – the first pediatric case in which severe anaphylaxis was encountered after intravenous gonadorelin acetate administration. An 8-year-old girl who was diagnosed with central precocious puberty was receiving triptorelin acetate treatment uneventfully for 6 months. In order to evaluate the efficacy of the treatment, an LH-RH stimulation test with gonadorelin acetate was planned. Within 3 min after intravenous administration of gonadorelin acetate, she lost consciousness and tonic seizures began in her hands and feet. She was immediately treated with epinephrine, diphenhydramine, and fluids. Her vital signs recovered within 30 min. Based on the results, anaphylaxis should be anticipated and the administration of these drugs should be performed in a setting that is equipped to deal with systemic reactions.

Hyperinsulinaemic hypoglycaemia (HH) is characterised by inappropriate insulin secretion and is the most common cause for persistent neonatal hypoglycaemia. The only treatment available for medically unresponsive hypoglycaemia is a near-total pancreatectomy. A neonate with severe HH, due to a homozygous ABCC8 mutation, was not responsive to treatment with maximal doses of diazoxide and subcutaneous daily octreotide, and underwent a near-total pancreatectomy; however, hypoglycaemia persisted. Introduction of sirolimus, an mTOR (mammalian target of rapamycin) inhibitor, obviated the requirement for glucose infusion. Euglycaemia was achieved with no significant adverse events from the drug. Sirolimus therapy was ceased at 13 months of age. No episodes of persistent hypoglycaemia were observed after cessation of sirolimus. This report demonstrates the successful use of sirolimus for persistent hypoglycaemia in the critically ill infant post pancreatectomy. Sirolimus could be considered in patients with severe HH not responsive to conventional medical and surgical therapy. However, the long-term efficacy and safety with this immunosuppressive drug in very young patients are not assured.