Band 27, Heft 7-8

Although the prevalence of childhood obesity is plateauing, it remains a social concern. The Japan Society for the Study of Obesity devised criteria for obesity disease as a morbid state that requires medical treatment in 2002. Moreover, the Japanese Ministry of Health, Labour and Welfare announced diagnostic criteria for childhood metabolic syndrome in 2010 because of the increasing number of children with lifestyle-related diseases. The treatment of obesity needs to be prioritized, and three principles, other than behavioral therapy, have been introduced in this study for the general medical treatment of obesity without underlying diseases: (1) diet therapy, (2) exercise, and (3) no pharmacotherapy. However, preventing obesity is more important than its treatment. A previous study reported the tracking of an overweight status from infancy; therefore, it is important to prevent infants from becoming overweight. The concept of the developmental origins of health and disease has been attracting more attention in recent years; however, preventative measures prior to birth should also be considered to reduce the incidence of obesity. Although the methods used to approach the treatment of childhood obesity change with differences in race or lifestyle, those who are engaged in the medical treatment of childhood obesity worldwide can contribute to its treatment and prevention by a mutual exchange of information.

Objective: Despite the high prevalence of vitamin D deficiency in adults worldwide, not many studies have evaluated the condition in adolescents. The present study was therefore conducted to assess the prevalence of vitamin D deficiency in a group of students from Shahroud, Iran. Methods: The cross-sectional descriptive analytical study was conducted on junior high and high school students of both genders from urban and rural areas of Shahroud, the largest city of Semnan Province in Iran, in winter 2011. The combination of stratified and cluster random sampling methods was applied in the study. A questionnaire on the demographic data, socioeconomic status, lifestyle habits (sun exposure, physical activity, dairy consumption), and drug and personal history was completed for each student. Blood samples were taken to assess vitamin D levels. Results: One thousand forty-seven students from four junior high and six high schools were recruited. From among them, 42.2% were boys and 57.8% were girls. Mean and standard deviation of vitamin D levels in the studied population were 14.7±9.4 ng/mL. Only 7.2% of the boys and 3.8% of the girls had sensible sun exposure. The median of milk consumption was 3 glasses per week, ranging from 0 to 7. Conclusion: It could be concluded that vitamin D deficiency is quite prevalent among the Iranian adolescents, and this is mainly because this group follows an unhealthy lifestyle due to osteoporosis.

Objective: The first aim of the present study was to analyze the body composition of Polish children ages 7–17 years old to add to the current body of literature. The second aim was to compare two body fat measurement methods (bioimpedance vs. Slaughter equation) on the abovementioned population. Methods: Height (cm) and weight (kg) of 308 (161 males and 147 females) participants, ages 7–17, were measured, and body mass index (BMI) scores were calculated. Skinfold thickness (SFT) was measured for the triceps, subscapular, abdominal, suprailiac, thigh, and medial thigh skin folds on the left side of the body. Fat mass, fat percentage in the whole body (%BF), fat-free mass, and total body water were assessed using bioelectrical impedance analysis (BIA). Results: In the present sample, 29.5% of males were overweight, and 11.3% of these were obese. Among females, 27.2% were classified as overweight, and 6.8% of these were obese. Males had a higher total body water (median=27.25 vs. 24.8 kg, p<0.001) and fat-free mass (median=37.25 vs. 33.90 kg, p<0.001), while females showed a higher total body fat percentage (median=22 vs. 14.55%, p<0.001) and fat mass (median=9.1 vs. 5.9 kg, p<0.001). %BF calculated using Slaughter equations overestimated those obtained by BIA in both genders (p<0.0001). Conclusions: The percent of youths classified as overweight and obese has increased in Krakow (Poland). Calculation of body fat percent derived from bioimpedance provides better estimates than the use of Slaughter equations, which tended to overestimates the values.

Objective: This study aims to evaluate the association of miR-33b / SREBP-1 rs8066560 with hyperglycemia and insulin resistance in Iranian children and adolescents. Methods: This case-control study comprised 200 participants with 9–19 years of age, consisting of 100 MetS and 100 healthy controls. Anthropometric and biochemical parameters were measured, and the polymorphism was genotyped by TaqMan real-time PCR method. Results: Logistic regression analysis of genotype distribution of rs8066560 did not show a significant association with MetS neither in boys (OR, 1.745; 95% CI, 0.695–4.382; p=0.236) nor in girls (OR, 1.075; 95% CI, 0.420–2.752; p=0.880). Participants with GG/AG genotypes had significant higher LDL-C levels than those with the AA genotype. No statistically significant difference was documented in fasting blood glucose and insulin levels between the three rs8066560 genotypes. Conclusions: We found that rs8066560 variant on SREBP-1 and miR-33b genes is associated with LDL-C levels; however, it may not be an important determinant for the MetS, hyperglycemia, and insulin resistance in children and adolescents.

Purpose/Background: To examine whether male and female caregivers of children with a disorder of sex development (DSD) differ in levels of anxious and depressive symptoms. Materials/Methods: Participants included 80 caregivers (40 males, 40 females) of 40 children with a DSD. Children were categorized based on illness characteristics including ambiguous genitalia, life-threatening, and life-threatening with ambiguous genitalia. Caregivers completed measures of anxious and depressive symptoms. Results: A significant caregiver×diagnosis interaction for anxious symptoms emerged, with male caregivers of children with both ambiguous genitalia and a life-threatening condition reporting significantly lower levels of anxious symptoms than female caregivers of the same children. Conclusions: The findings are surprising because of the low level of anxious symptoms reported by male caregivers of children with a complex DSD. It is possible that they have disengaged themselves from the child and/or diagnosis, causing their female counterparts to take on more responsibility.

Background: Nesfatin-1, a recently discovered anorexigenic peptide, is expressed in several tissues, including pancreatic islet cells and central nervous system. However, its pathophysiological role in the development of obesity and insulin resistance remains unknown. Aim: To investigate the possible involvement of nesfatin-1 in the pathogenesis of childhood obesity, we examined the relationship between fasting and postprandial nesfatin-1 concentrations and metabolic/antropometric parameters in obese children. Material and methods: The study included obese children with a body mass index >95th percentile. Fasting serum glucose, insulin, lipid profile, fasting and postprandial (120th min) nesfatin-1 levels were measured to evaluate the metabolic parameters. Different cutoff values for prepubertal and pubertal stages were used to determine the status of insulin resistance (HOMA-IR) (prepubertal >2.5, pubertal >4). The percentage of body fat was measured using bioelectric impedance analysis. Results: Seventy-one obese children were included in this study. There was no statistically significant difference between fasting and postprandial nesfatin-1 levels in obese subjects (0.70±0.15 and 0.69±0.14 ng/mL, p>0.05, respectively). Insulin resistance was observed in 58% (41/71) of the cases. There was no significant difference in either fasting or postprandial serum nesfatin-1 levels between the insulin-resistant and non-resistant groups (p>0.05). There was no correlation between fasting and postprandial serum nesfatin-1 levels and anthropometric and metabolic parameters in insulin-resistant and non-resistant groups. Conclusions: In this study, there was no significant increase in the postprandial level of nesfatin-1. This observation suggested that oral glucose load in obese children may not be sufficient for nesfatin-1 response and that nesfatin-1 may not have an effect as a short-term regulator of food intake.

Background: Idiopathic short stature (ISS) is short stature of unknown cause. In 2003, the Food and Drug Administration (FDA) approved the use of growth hormone (GH) for ISS. Several studies have evaluated the effect of GH in children with ISS, in whom improved growth velocities and height standard deviation scores (SDS) have been reported. However, clinical variables influence the height improvement. Objective: This study aimed to evaluate the effects of GH treatment on ISS and to analyze clinical factors associated with growth velocity. Materials and methods: This study was conducted retrospectively. Subjects diagnosed with ISS at Ajou University Hospital were divided into two groups, an ISS with GH-treatment group (n=34) and an ISS control group (n=36). All children were prepubertal, and aged <10 years. We reviewed their auxological data, laboratory findings, and bone age. Results: Growth velocity of the GH-treatment group exceeded that of controls by 3.37 cm/year (95% CI, 2.78–3.95). At baseline, the mean SDS for height in the treatment and control groups were equivalent (–2.25±0.29 and –2.22±0.31, respectively). However, after 1 year, the height of the GH-treated group exceeded that of the control group by 0.73 SDS (95% CI, 0.57–0.88). A negative correlation was found between age and growth velocity in the GH-treatment group. Conclusion: GH treatment increased short-term growth velocity and height SDS of Korean children with ISS. Age was identified as the single most important factor correlated with growth velocity in GH treatment.

Objective: To determine the demographic and clinical characteristics of type 1 diabetes (T1D) in the past two decades, and to analyze changing trends over the past 40 years. Methods: Patients with a diagnosis of T1D in 1990–2010 were included. Patients diagnosed in the first half of the period comprised Period I, and those from the second half comprised Period II. Age at onset, gender, seasonal distribution, infectious etiology, and clinical picture at onset are analyzed and compared in two periods. In addition, we compared these data with that of the preceding two decades (1969–1991), which was reported in a previous publication. Results: A total of 354 children with T1D were included in the study. The median age at diagnosis of T1D was 7 years in the period 1990–2010 in comparison to 9.5 years during the period 1969–1991. Patients were diagnosed mostly in winter and autumn, and 32.3% of the children had an infection at the time of diagnosis. Frequency of diabetic ketoacidosis was 50.8% at diagnosis. The peak age at onset was 4 to 6 years. Conclusions: Our study provides substantial information about the clinical characteristics of Turkish children. The age of onset of T1D decreased in the past 20 years, as observed in other parts of the world. Our findings also suggest seasonality at onset of T1D. This study shows the changes of demographic and clinical characteristics of T1D in central and northeastern parts of our country over a 40 year period.

Recent studies reported that gamma-glutamyltransferase (GGT) and beta 2-microglobulin (β2M) are possible markers of cardiovascular disease in adults, however, their roles among children have not been fully elucidated. We have examined the relationships of GGT and β2M on C-reactive protein (CRP) among 326 healthy elementary school children. To investigate the relationships of serum GGT and β2M levels on measuring of CRP, multiple regression analysis and analysis of covariance (ANCOVA) were performed. After being adjusted for confounders, body mass index, log-transformed GGT, and β2M were significantly related to CRP. Independent of other risk factors, ANCOVA showed that serum β2M levels were significantly associated with serum CRP (p=0.012, p for trend <0.001), and GGT levels had similar results (p=0.211, p for trend=0.035). These results suggest that serum β2M and GGT levels are useful indicators for evaluating the occurrence of slight inflammation as background, which promotes atherosclerosis even in healthy children.

Objective: The study aimed to determine the incidence of metabolic syndrome (MS) in a group of Czech obese children, to evaluate the incidence of insulin resistance according to HOMA-IR in this group, and to consider the diagnostic value of HOMA-IR in early MS detection in obese children using the logistic regression models for analyzing the relations between HOMA IR and MS. Subjects and Methods: Anthropometric and laboratory examinations were performed in a group of 274 obese children aged 10–17 years. Results: MS was established in 102 subjects (37%). The presence of insulin resistance according to HOMA-IR >3.16 was ascertained in 53% of the subjects. HOMA-IR limit was exceeded by 70% in the MS (+) group and by 43% in children in the MS (–) (p<0.0001) category. Conclusion : The relatively high incidence of insulin resistance in obese children without MS questions the prevailing diagnostic criteria of, perhaps, falsely excluding some cases of, MS.

Vitamin D status is best reflected by circulating concentrations of 25-hydroxyvitamin D 2 and D 3 (25-OH-D). An adequate blood concentration of total 25-OH-D is commonly defined as that which maintains parathyroid hormone (PTH) within the normal range. Consensus from studies of adults with renal impairment indicates that 75 nmol/L of 25-OH-D maintains suppression of PTH. No similar consensus exists in children. We studied the correlation of PTH and 25-OH-D in 271 patients aged 2 months to 21 years (mean 11 years) in a tertiary care pediatric setting. Patients with renal impairment were excluded by elevated creatinine concentration and chart review. PTH did not significantly correlate with 25-OH-D concentrations >25 nmol/L. PTH was significantly elevated in specimens with <25 nmol/L of 25-OH-D (p=10 –17 ). Using PTH suppression as indicator, these data suggest that 25-OH-D concentrations >25 nmol/L in children indicate vitamin D sufficiency.

Background: The aim of our study was to evaluate the associations between vitamin D deficiency, the atherosclerosis and metabolic syndrome. Methods: Two hundred and forty-seven obese children and adolescents, 8–16 years of age (body mass index>95 p) were included in the study. Anthropometric measurements, blood pressure measurements, lipid profile, vitamin D level and carotid intima media thickness (c-IMT) were measured. MS was diagnosed according to IDF criteria. Results: The prevalance of vitamin D deficieny in obese children and adolescent was 46.6%. Low levels of vitamin D were associated with increased carotis intima media thickness and metabolic syndrome (p=0.03, p=0.04, respectively). For clinical cardiovascular risk factors, mutivariable regression analyses showed that low vitamin D level was best predictor of c-IMT. Conclusions: In this study we showed an association between low vitamin D status and atherosclerosis independent of traditional risk factors in obese children and adolescents.

Objective: Oxidative stress has been reported to be involved in the pathogenesis of metabolic disorders related with obesity. The aim of the study was to investigate the association of oxidative stress and paraoxonase activities with non-alcoholic fatty liver disease (NAFLD) as well as metabolic syndrome. Materials and methods: A total of 109 obese children and adolescents and 44 healthy and lean control subjects were enrolled in the study. According to their ultrasonographic steatosis scores, they were classified into four groups as follows: healthy children; obese, non-NAFLD; obese, grade I-NAFLD; and obese, grade II–III NAFLD. The biochemical parameters and insulin resistance (HOMA-IR) were evaluated from fasting samples. The plasma total antioxidant status (TAS), total oxidant status (TOS), and serum paraoxonase activities were measured and then oxidative stress index (OSI) was calculated as the indicator of degree of oxidative stress. Results: As the steatosis increased, the alanine aminotransferase, C-reactive protein, HOMA-IR, total cholesterol, and LDL cholesterol increased, whereas HDL cholesterol decreased. The TAS measurements were higher in the obese NAFLD group compared with that of the healthy control group. The TOS and OSI measurements did not differ between the groups. Paraoxonase activities increased significantly as steatosis increased. Conclusions: Among the children in this study, no relationship could be demonstrated between obesity with/without steatosis and oxidant/antioxidant status.

Objective: The aim of this study was to evaluate clinical manifestations, laboratory findings, and effects of antithyroid drugs in younger children with Graves’ disease (GD). Design: A retrospective and collaborative study. Setting: Nine facilities in Chiba prefecture, Japan. Patients: We analyzed 132 children and adolescents with GD. The subjects were divided according to the median age into a group of young children (group I, 4.1–12.4 years, n=66) and an adolescent group (group II, 12.5–15.9 years, n=66). Main outcome measures: Clinical manifestations, laboratory findings, incidence of adverse effects, and remission rates 5 years after initial therapy were assessed. Results: The mean height SD score of group I (1.0) was higher than that of group II (0.3, p<0.001). The mean BMI SD score of group I (–0.7) was lower than that of group II (–0.3, p<0.05). The most common presentations were goiter, sweating, and hyperactivity in group I, whereas the most common presentations were goiter, sweating, and easy fatigability in group II. Hyperactivity was more frequent in group I (56.7%) than in group II (37.9%, p<0.05). Liver dysfunction appeared more often in group I (14.3%) than in group II (1.9%, p<0.05). There was no difference in the appearance of adverse effects between the two groups. The remission rate was slightly lower in group I (23.1%) than in group II (31.3%), but was not significant. Conclusions: Thyrotoxicosis had more influence on the growth and liver function in younger children.

Objective: The aim of this study was to assess possible associations between potential risk factors for fractures and their occurrence in otherwise healthy Greek male adolescents. Subjects: A total of 63 male adolescents participated in the study, 21 males with a history of at least one fracture and 42 healthy male controls. Methods: Each participant was assessed for physical and pubertal status, hormonal profile, bone mineral density, bone turnover indices, and dietary habits. Results: The lower bone mineral density-z scores and increasing testosterone and serum collagen type 1 cross-linked C-telopeptide levels were related to fracture risk, whereas increased insulin-like growth factor-1, soluble receptor activator of nuclear factor kappa-B (factor-κB) ligand, and soluble receptor activator of nuclear factors-κB ligand/osteoprotegerin levels were protective for fractures. Conclusions : The findings indicate a potential ‘added value’ of hormonal parameters and bone markers to bone mineral density for evaluating fracture risk in healthy male adolescents.

Aim: Obesity is the major determinant of metabolic syndrome. Being born small for gestational age (SGA) may be co-responsible. We aimed at evaluating the association between 1. obesity and 2. being born SGA and the presence of endocrine-metabolic abnormalities in prepubertal Slovak children. Methods: The study included 98 children, aged 3–10.9 years: 36 AGA-born obese children (OB), 31 SGA-born children (SGA) and 31 appropriate for gestational age born non-obese children (AGA). Fasting serum levels of glucose, total cholesterol, LDL, HDL, triglycerides, fT4, TSH, cortisol and insulin were determined. HOMA-IR was calculated. Personal data about birth weight and length and family history were collected. Actual anthropometric measurement was done. Results: In every group, high prevalence of positive family history of metabolic disorder was found. In comparison with AGA children, OB children were taller (p<0.01) with higher body mass index (BMI) (p<0.001), and had increased insulin levels and homeostasis model assessment for insulin resistance (HOMA-IR) (p<0.001), decreased high-density lipoprotein (HDL) (p<0.001), and a trend to higher cortisol levels (p=0.069) was noted. SGA-born children were shorter (p<0.001), with BMI comparable to the AGA group. They had higher glucose levels (p<0.001), a trend to decreased HDL levels (p=0.085) and increased fT4 levels (p<0.001). A three-fold higher occurrence of metabolic abnormalities was present in obese children and twice more metabolic abnormalities were present in SGA-born children in comparison with AGA-born children. Conclusions: SGA-born children are more prone to developing endocrine-metabolic abnormalities than non-obese children born AGA, but they are at less risk than obese AGA-born children. We should provide specialized care for obese children already in prepubertal age and pay attention to SGA-born children.

A correlation has been clearly shown between inflammation markers and subclinical atherosclerosis markers in the early stages of atherogenesis in subjects with familial hypercholesterolemia (FH). The aim of this study was to investigate potential inflammation markers in the diagnosis of atherosclerosis in children with FH. A total of 48 dyslipidemic children and 24 healthy age-matched control subjects were taken into study. Inflammation and macrophage activation markers (hsCRP, myeloperoxidase, chitotriosidase, YKL-40, TNF-α, IL-6, IL-18, MMP-1 and MMP-9) and lipid parameters of all patients were measured. Carotid intima-media thickness (cIMT) and flow-mediated dilation (FMD) levels were determined. Our data suggested that clinically evidenced (by cIMT and FMD levels) atherosclerosis starts in the early ages in hypercholesterolemic children. Higher cholesterol levels strongly correlated with macrophage activation markers (ChT, YKL-40 and myeloperoxidase). ChT and YKL-40 seem to be the more predictable markers of atherosclerosis even in early ages (<6 years old) than other classical inflammation markers such as hs-CRP, IL-6 and TNF-α.

The aim of the study was to determine if cardiovascular autonomic neuropathy (CAN) is associated with changed concentration of exhaled carbon monoxide (eCO) in adolescents with type 1 diabetes (T1D). A total of 46 T1D patients and 25 healthy controls (15–19 years) were enrolled. The parameters eCO and carboxyhemoglobin (HbCO) were established using a MICRO-4 Smokerlyser. CAN was examined by standard cardiovascular tests. Adolescents with T1D did not significantly differ in eCO compared to healthy subjects. eCO and HbCO were significantly lower in CAN-positive subjects (n=19) (1.36±1.65 ppm vs. 3.09±2.31, p=0.01 and 0.58±0.49% vs. 1.04±0.44, p<0.01, respectively) compared to CAN-negative subjects (n=27), whereas no significant difference was found in other measured parameters. By multivariate logistic regression, eCO and HbCO were associated with higher risk of CAN (OR=1.824, p<0.05 and OR=10.989, p<0.01). Our results indicate that eCO is decreased in CAN-positive diabetic subjects. Further studies are necessary to investigate the possible role of eCO as a marker for CAN.

Aim: To investigate changes of gut hormones in term and preterm infants in the first 2 months after birth, as the role and relationships of gut hormones in premature infants has not been well elucidated. Methods: In 29 preterm and five term infants, fasting serum concentrations of leptin, glucose-dependent insulinotropic polypeptide (GIP), glucagon-like peptide-1 (GLP-1), peptide YY (PYY), pancreatic polypeptide, insulin, amylin, and ghrelin were measured using a bead array system. Results: Serum leptin concentration soon after birth showed a positive correlation with gestational week in all infants (r=0.623, p<0.01). Serum leptin level rapidly decreased in all infants. In preterm infants, serum GLP-1 levels at birth showed negative correlations with gestational week (r=–0.447, p=0.02). Serum GIP, GLP-1, and PYY levels increased after birth and were persistently high until 10 weeks of life. Conclusion: Serum concentrations of different gut hormones changed postnatally in their specific ways in preterm infants.

Background: Aromatase inhibitors (AIs) have been used off-label to increase adult height in short adolescent males. Studies have shown that AIs increase the predicted adult height (PAH) while delaying bone age (BA) maturation. We sought to determine whether AI therapy increases PAH in boys with short stature or rapid pubertal progression, and to evaluate any untoward effects. Methods: The charts of 27 boys with BA ≥13 and short stature [height ≥2 standard deviation (SD) below the mean or ≥2 SD below mid-parental target height (MPTH)] or rapid pubertal progress, treated with anastrozole were reviewed. Outcome measures included anthropomorphic, hormonal, and metabolic data. Results: The AI therapy averaged 21 months (range 14–30 months) for all, with Rx group 1 receiving <18 months therapy (n=7) and Rx group 2 receiving 18–30 months therapy (n=20). Post-therapy, in Rx group 1 and all subjects, there was no significant change in the PAH, height SDS, or BA/chronological age (CA). In Rx group 2, there was a small, nonsignificant increase in PAH, no change in height SDS, and a small decrease in BA/CA. Post-therapy PAH was different from MPTH in all and in both Rx groups 1 and 2, p<0.02. Eight of them achieved near-final height, averaging 6.73±1.40 cm less than MPTH and 1.91±0.86 cm less than the pre-therapy PAH. Post-therapy, the initially decreased estradiol did not persist but mildly increased testosterone and decreased high-density lipoprotein were noted, as was an increase in hematocrit, and decrease in growth velocity. Conclusions: We suggest that although bone age progression may be slightly delayed with longer duration of therapy, an overall short-term AI therapy does not lead to a final height that is greater than the predicted pre-therapy height.

Congenital hypothyroidism (CH) is the most common neonatal endocrine disorder and 2% of cases have a familial origin. Our aim in this study was to determine the genetic alterations in two siblings with CH coming from a consanguineous family. As CH is often inherited in an autosomal recessive manner in consanguineous/multi case-families, we first performed genetic linkage studies to all known causative CH loci followed by conventional sequencing of the linked gene. The family showed potential linkage to the TSHR locus and our attempts to amplify and sequence exon 2 of the TSHR gene continuously failed. Subsequent RT-PCR analysis using mRNA and corresponding cDNA showed a large deletion including the exon 2 of the gene. The deletion was homozygous in affected cases whilst heterozygous in carrier parents. Here we conclude that CH in both siblings of this study originates from a large deletion including the exon 2 of the TSHR gene. This study demonstrates that full sequence analysis in a candidate CH gene might not always be enough to detect genetic alterations, and additional analyses such as RT-PCR and MLPA might be necessary to describe putative genetic causes of the disease in some cases. It also underlines the importance of detailed molecular genetic studies in the definitive diagnosis and classification of CH.

Aim: Steroid responsive encephalopathy with autoimmune thyroiditis (SREAT) is a clinically and electrographically heterogeneous steroid-responsive encephalopathy associated with thyroid autoantibodies. We report an adolescent with SREAT and review PubMed literature relating to childhood. Methods: A 14-year-old boy, without any preceding history of trauma, meningoencephalitis or seizures, was admitted in a comatose state. A similar episode of loss of consciousness 2 months prior with normal neuroimaging and electroencephalogram (EEG) had been followed by behavioral alterations. A year previously, during evaluation for increased appetite and poor weight gain, he was noted to have small goitre with thyroid-stimulating hormone (TSH) 7.26 mIU/L, T3 1.232 nmol/L, and T4 117.63 nmol/L. Routine hemogram, blood biochemistry, thyroid function tests including free hormone levels, ultrasonography thyroid and magnetic resonance imaging were normal. EEG showed diffuse slowing of all waves. Cerebrospinal fluid showed no pleocytosis and electrophoresis showed oligoclonal band. Viral studies and serum N-methyl-D-aspartate receptor antibody levels were negative. Anti-thyroid peroxidase (Anti-TPO) antibodies were raised. Intervention was with intravenous dexamethasone 4 mg every 6 h for 1 week followed by tapering schedule of oral prednisolone over 6 months. Results: He regained consciousness after the second dose of dexamethasone and was discharged on day 7 in a fully conscious and ambulant state on a tapering course of low dose prednisolone for 6 months. He remains euthyroid with normal sensorium and behavior at 18 months follow-up. Only 50 cases below 18 years age were identified amongst 300 PubMed articles up to 31 July 2013. Conclusion: Prompt steroid therapy following early recognition by high clinical suspicion and measurement of antithyroid antibody titers can lead to a favorable prognosis in SREAT.

Neonatal diabetes is defined as an uncontrolled hyperglycemic state occurring within the first 6 months of life. It is a rare disease with an incidence of 1 to 90,000–250,000. It is usually a disease of genetic origin in which insulin gene mutations play the main role in the disease process. A baby, born to a mother who had previously been diagnosed with type 1 diabetes mellitus at 14 months of age, had a high blood sugar level within the first few hours after birth and was subsequently diagnosed as having neonatal diabetes mellitus. Baby and mother were identified as having a novel heterozygous insulin missense mutation, p.C109R. Difficulties occurred in both follow-up and feeding of the baby. Without the addition of the mother’s milk, an appropriate calorie milk formula and isophane insulin were used for the baby during follow-up. Multiple mechanisms are responsible in the pathogenesis of neonatal diabetes mellitus. Insulin gene mutations are one of the factors in the development of neonatal diabetes mellitus. If a resistant hyperglycemic state persists for a long time among babies, especially in those with intrauterine growth retardation whose mothers are diabetic, the baby concerned should be followed-up carefully for the development of neonatal diabetes mellitus.

Type 1 diabetes mellitus (T1DM) is one of the most common chronic diseases in childhood and is caused by insulin deficiency resulting from the autoimmune destruction of insulin producing beta cells of the pancreas. Most children in the US with new onset T1DM present with the classic signs and symptoms of hyperglycemia and 30% with diabetic ketoacidosis (DKA). Neurologic manifestations are relatively rare and mostly include lethargy, decreased level of consciousness, and coma as a result of DKA. In this article, five cases of new onset T1DM with exceedingly rare or unreported neurologic manifestations in the pediatric age group are presented, along with a review of the literature.

Background: Williams-Beuren syndrome (WBS) is a rare genetic disorder caused by the deletion of 26–28 genes on chromosome 7. Fifteen percent of WBS patients present with hypercalcaemia during infancy, which is generally mild and resolves spontaneously before the age of 4 years. The mechanisms underlying the transient hypercalcaemia in WBS are poorly understood. Case: We report a case of severe symptomatic hypercalcaemia in a patient with WBS, in which treatment with mild calcium restriction, hyperhydration and repeated bisphosphonate administration only resulted in short-lasting effects. Long-term lowering of serum calcium was only achieved after reducing calcium and vitamin D intake to the bare minimum. Conclusions: This case illustrates the potential severity of hypercalcaemia in WBS, and demonstrates that both the cause as well as the solution of this problem may be found in the intestinal absorption of calcium. We hypothesise that the phenotypical resemblance between WBS and transient idiopathic infantile hypercalcaemia can be explained by similarities in the underlying genetic defect. Patients suffering from transient infantile hypercalcaemia were recently described to have mutations in CYP24A1, the key enzyme in 1,25-dihydroxyvitamin D 3 degradation. In the light of this new development we discuss the role of one of the deleted genes in WBS, Williams syndrome transcription factor ( WSTF ) , in the etiology of hypercalcaemia in WBS.

Vitamin D (VitD) intoxication, a well-known cause of hypercalcaemia in children, has renal, cardiac and neurological consequences. Iatrogenic or accidental administrations are the most common causes. We present two cases of hypervitaminosis D due to over-the-counter VitD supplement self-medication. A 12-year-old boy was hospitalised for abdominal pain, constipation and vomiting. Routine biochemistry indicated severe hypercalcaemia and renal failure. Plasma 25-OH VitD level was very high and parathyroid hormone was suppressed. Renal ultrasound showed nephrolithiasis. Hydration, diuretics and prednisone induced a progressive reduction of calcium levels. His brother, who was receiving the same treatment, was hospitalised although asymptomatic. Normal serum calcium and renal function were revealed, while 25-OH VitD was high and parathyroid hormone was suppressed. Renal ultrasound was within the normal range. Examination of the VitD content of the over-the-counter supplement revealed a higher amount than declared. VitD administration implies several risks and must be prescribed only when needed and under strict medical control.

Background: As neonatal central diabetes insipidus is rare in preterm neonates with intraventricular hemorrhage (IVH), very little is known about dosing and the route of administration of desmopressin treatment. Case report: We present a preterm neonate born at 29 weeks’ gestation. Within 24 h, she developed bilateral IVH with subsequent post-hemorrhagic hydrocephalus. On the 3rd postnatal day, she developed diabetes insipidus for which she was intranasally administered 0.2 mg desmopressin. This resulted in oliguria with several hours of anuria and a 25-point drop in sodium levels within 15 h. Conclusion: The determination of the desmopressin dose in a preterm neonate is a challenge and there is no consistent literature about the dosing or the route of administration. We suggest starting with a low dose of intranasal desmopressin (0.05–0.1 μg) and titrate in accordance with clinical and laboratory parameters.

Background: Multiple endocrine neoplasia type 1 (MEN1) is an inherited neoplasia syndrome that generally presents with hypercalcaemia due to hyperparathyroidism. Insulin-producing tumours are less common components of the syndrome that emerge later during the course of the disease. We report here a case of an adolescent who presented with symptomatic hypoglycaemia as the first indication of MEN1. Case: A 14-year-old boy, known to use illicit drugs, was brought to the hospital with altered mental status. He was hypoglycaemic and further investigations revealed two pancreatic insulinomas. Despite having no relevant family history, genetic evaluation showed a mutation consistent with MEN1. Conclusion: Insulinomas in adolescents are generally rare and even less common as a first presentation of MEN1. This diagnosis carries implications for potential future neoplasms, both benign and malignant. While intoxication is a more common case of altered mental status in adolescents, clinicians must maintain a high index of suspicion for organic disease.

Background: Holoprosencephaly (HPE), the most common malformation of the brain, results from failed or incomplete separation of the embryonic forebrain (prosencephalon). HPE occurs in approximately 1 in 250 embryos and in about 1 in 10,000 births. It is etiologically heterogeneous, and may be caused by cytogenetic anomalies and teratogenic influences; it occurs as part of a syndrome, or due to heterozygous mutations in 1 of over 10 HPE-associated genes. ZIC2 mutations are the second-most common cause of non-syndromic non-chromosomal HPE (after sonic hedgehog ) and occur de novo in 74% of the affected probands. Objective: The objective of the study was to describe the first case of ZIC2 -related HPE with both anterior and posterior pituitary insufficiencies. Case presentation: We report about a 2-year-8-month-old boy who was born as a second child in a non-consanguineous healthy Turkish family. He has the characteristic ZIC2 phenotype: bitemporal narrowing, upslanting palpebral fissures, large ears, short nose with anteverted nares and broad and deep philtrum. Magnetic resonance imaging revealed alobar HPE. During laboratory investigation, his blood sodium level was 158 mmol/L and the specific gravity of his urine was 1.002. Serum osmolarity was 336 mOsm/L and urine osmolality was 135 mOsm/kg. His FT4 was 0.8 ng/dL and TSH was 0.79 mLU/mL. Response to vasopressin confirmed the diagnosis of central diabetes insipidus and TRH-stimulating test supported the central hypothyroidism. A frameshift mutation (NM_007129.2:c1091_1092 del, p.Gln364Leufs*2) in the ZIC2 gene was detected. Conclusion: Pituitary insufficiency other than isolated diabetes insipidus is a rare finding of HPE, and occurs most frequently in patients with GLI2 mutations (the phenotype of which typically does not include frank neuroanatomic anomalies such as HPE); ours is the only described patient with a ZIC2 mutation and both anterior and posterior pituitary dysfunction.

A 4-year-old boy with hypochondroplasia was admitted to our clinic with complaints of bronchopneumonia. He also had immune deficiency characterized by low CD3, CD4 T-lymphocyte subsets and a low level of serum immunoglobulin A (IgA). The diagnosis of hypochondroplasia was made on clinical, radiological, and laboratory findings by the pediatric endocrinology department. The focus of our study is hypochondroplasia associated with immune deficiency which was unpublished in English medical literature previously.

We report a girl who presented with clinical and biochemical features of hypophosphatemic rickets. Mutational analysis detected a heterozygous nonsynonymous sequence variation in exon 11 of the PHEX gene (NM_000444.4:c.1216T>C, NP_000435.3:p.Cys406Arg). This previously undescribed PHEX mutation is probably the cause of renal phosphate wasting in our patient that resulted in rickets.

Autoimmune polyglandular syndrome (APS) is a rarely diagnosed condition characterized by a combination of two or more organ-specific autoimmune diseases and divided into a very rare juvenile (APS type I) and a relatively common adult type (APS II–IV). The major components of APS-I are hypoparathyroidism, adrenal failure, and mucocutaneous candidiasis. In addition to the classic triad, many other autoimmune diseases could be associated with the syndrome. We report an adolescent patient with psoriasis vulgaris and APS-I.

Tyrosinemia type I (HT1) is a genetic metabolic disorder characterized by progressive liver disease, kidney disease, and rickets. The disease is caused by mutations in the FAH gene that results in deficiency of fumarylacetoacetase, an enzyme that is involved in the tyrosine degradation pathway. We investigated the clinical characteristics and molecular cause of HT1 in an affected family from Iran. Molecular analysis identified a homozygous combined missense (c.G1009G>A, p.Gly337Ser) and aberrant splicing mutation removing the first 50 nucleotides of exon 12. This mutation was only described in HT1 patients from Scandinavian countries and this is the first report from another population. Although failure to thrive is one of the typical features in HT1, our proband, similar to the reported Scandinavian patients, had normal growth and development. The results of this study have applications in patient screening and genetic counselling.