Diabetes care at school has recently appeared on the agenda of international diabetes organizations, the basic principles of which have been newly determined. The aim of this review was to summarize the activities and output of the Diabetes at School Program - a program that has been delivered in Turkey for the last 10 years - and to focus on different aspects of Diabetes Care at School through a national model. Recently, a detailed set of national regulations, including the basic principles proposed by the International Society for Pediatric and Adolescent Diabetes and the experience in Turkey, was prepared and has come into force. The future agenda includes giving priority to socio-economically disadvantaged regions, provision of an Individual Treatment Plan at School for each child with diabetes and ensuring that each school has an action plan for the care of children with diabetes. We believe that if all countries have programs and structured national regulations similar to the Diabetes at School Program, this will enable significant progress in the level of care delivered to children with diabetes.

Objective: Bisphenol A (BPA) is a known endocrine disruptor and free BPA will interact with estrogen. BPA is also fat soluble and will therefore contaminate breast milk. The European Food Safety Authority has set a limit for temporary tolerable daily intake of 4 µg/kg body weight/day in breastfeeding infants. The aim of this study was to measure human milk BPA concentrations in Turkish women and thus exclusively breastfed infants’ exposure to BPA.
Methods: Healthy, postnatal, exclusively breastfeeding women were recruited and breast milk samples were collected. Free BPA concentration was analyzed in the milk samples using competitive enzyme-linked immunosorbent assay. Participants’ demographic characteristics and nutritional habits were investigated through face-to-face interviews using a detailed questionnaire.
Results: Eighty women participated. Median milk free BPA level was 0.63 µg/L. There was no statistically significant association between maternal body mass index, birth type, parity, infant birth week, infant birth weight, and human milk BPA concentration. Nevertheless, there was a significant association between human milk BPA level and consumption of fast-food and carbonated drinks (p=0.022 and p=0.018, respectively). Exclusively breastfed infants’ mean BPA exposure was 0.0099±0.0079 µg/kg bw/day. There was a moderate negative significant correlation between infant BPA exposure and infant current body weight (r=0.327, p=0.003).
Conclusion: BPA exposure in exclusively breastfed infants was within accepted limits and the current dietary exposure level of infants in this cohort was safe.

Objective: Late neonatal hypocalcemia (LNH) is a common metabolic problem associated with hypoparathyroidism, high phosphate intake and vitamin D deficiency, often presenting with seizures. In this cross-sectional study, we aimed to evaluate the role of vitamin D deficiency in LNH in Turkey and to describe the characteristics of affected newborns.
Methods: Conducted with a cross-sectional design and with the participation of 61 neonatal centers from December 2015 to December 2016, the study included term neonates with LNH (n=96) and their mothers (n=93). Data were registered on the FAVOR Web Registry System. Serum samples of newborns and mothers were analyzed for calcium, phosphate, magnesium, albumin, alkaline phosphatase, intact parathyroid hormone (iPTH) and 25 hydroxyvitamin D [25(OH)D] levels.
Results: The median (range) onset time of hypocalcemia was 5.0 (4.0-8.0) days of age, with a male preponderance (60.4%). The median (range) serum 25(OH)D levels of the neonates and their mothers were 6.3 (4.1-9.05) and 5.2 (4.7-8.8) ng/mL, respectively. The prevalence of vitamin D deficiency (<12 ng/mL) was high in both the neonates (86.5%) and mothers (93%). Serum 25(OH)D levels of the infants and mothers showed a strong correlation (p<0.001). While the majority (93.7%) of the neonates had normal/high phosphorus levels, iPTH levels were low or inappropriately normal in 54.2% of the patients.
Conclusion: Vitamin D deficiency prevalence was found to be high in LNH. Efforts to provide vitamin D supplementation during pregnancy should be encouraged. Evaluation of vitamin D status should be included in the workup of LNH.

Objective: Free hormones are biologically more active in target tissues. Thus, measurement of vitamin D taking into account bioavailability and free vitamin D may be preferable, especially when evidence is contradictory, as in obese children. In order to assess bioavailablity and free vitamin D, using a previously reported formula, vitamin D-binding protein (VDBP) level was measured and VDBP polymorphisms were also evaluated because of variations in binding affinity.
Methods: Eighty-four obese and 78 healthy children were included. Anthropometry, calcium, phosphorus, alkaline-phosphatase, parathyroid hormone (PTH), 25 hydroxyvitamin D [25(OH)D], bioavailable-free vitamin D, and VDBP concentration and polymorphism were evaluated in the whole group.
Results: Obese girls had significantly higher PTH than normal weight girls (p=0.001). Regardless of gender, obese children had significantly higher concentrations of VDBP (p=0.008) and PTH (p=0.002). When samples taken in winter were analyzed, PTH and VDBP were found to be higher and bioavailable and free vitamin D lower in the obese group. There was no difference in terms of total vitamin D between groups during the winter season.
Conclusion: While total, free, and bioavailable vitamin D in the obese group was similar to the control group in autumn, free and bioavailable vitamin D in the winter was lower in the obese than the control group. In addition, PTH was higher in the obese group in both autumn and winter. Therefore, more research is needed to evaluate the variability of free and bioavailable vitamin D according to body habitus, season and the effect any differences may have.

Objective: Neutrophil gelatinase-associated lipocalin (NGAL) is one of the new biomarkers for detecting acute renal injury. There are studies showing the relationship between NGAL and renal injury in obese children. The aim of this study was to investigate whether urinary levels of NGAL, kidney injury molecule-1, and serum cystatin C are increased in insulin resistance (IR) patients before the development of diabetes.
Methods: Cross-sectional, case-controlled study that included non-diabetic obese children and adolescent patients with IR and a nondiabetic obese control group with no IR, who attended a tertiary center pediatric endocrinology outpatient clinic between 2016-2018. Those with diabetes mellitus and/or known renal disease were excluded. NGAL and creatinine (Cr) levels were evaluated in the morning spot urine from all participants. Serum renal function was evaluated.
Results: Thirty-six control and 63 IR patients were included in the study, of whom 68 (68.7%) were girls. The mean age of all participants was 13.12±2.64 years and no statistically significant difference was found between the two groups in terms of age or gender distribution. Median (range) spot urinary NGAL (u-NGAL) values in the IR group were significantly higher at 26.35 (7.01-108.7) ng/mL than in the control group at 19.5 (3.45-88.14) ng/mL (p=0.018). NGAL/Cr ratio was also significantly higher in the IR group compared to the control group (p=0.018).
Conclusion: Obese pediatric patients with IR were shown to have elevated levels of u-NGAL, a marker of renal injury. u-NGAL examination may show early renal injury before development of diabetes.

Objective: Turner syndrome (TS) patients are at high risk of cardiometabolic disorders. Cardiometabolic risk factors are more commonly related to visceral rather than total body adiposity. Adipocytokines have been explored as a potential link between obesity and obesity-related cardiometabolic dysfunction. This study explored the validity of epicardial fat-thickness (EFT) and perihepatic fat-thickness (PHFT) measurement as cardiometabolic-risk predictors in TS-girls in relation to standard obesity-indices and metabolic syndrome (MetS) components.
Methods: Forty-six TS girls and twenty-five controls (10-16 years) were subdivided into two age-groups (10 to less than 13 and 13-16). Participants were assessed for body mass index (BMI) Z-scores, waist circumference (WC), total-fat mass (FM) and trunk-FM by bioimpedance-technique, EFT and PHFT by cardiovascular magnetic resonance, lipid-profile, homeostasis model assessment of insulin resistance (HOMA-IR), and serum chemerin. MetS was defined according to International Diabetes Federation criteria.
Results: Overweight/obesity and MetS were detected in 45.7% and 37% of TS-girls respectively. BMI Z-score, WC, total-FM, trunk-FM, EFT and PHFT values were significantly higher in TS-age groups compared to age-matched control groups, being more pronounced in the older group when TS-girls had been exposed to estrogen. Dyslipidemia, higher HOMA-IR, chemerin, EFT and PHFT values were observed in lean-Turner compared to BMI-Z-matched controls. EFT and PHFT were significantly correlated with chemerin and several components of MetS. EFT at a cut-off-value of 6.20 mm (area under the curve=0.814) can predict MetS in TS-girls.
Conclusion: TS-girls displayed an adverse cardiometabolic profile during late childhood and adolescence. EFT and PHFT are emerging cardiometabolic risk predictors in TS-patients. Excess EFT rather than total body adiposity may contribute to altered metabolic profile among lean-Turner patients.

Objective: To evaluate the clinical features and etiology of precocious puberty (PP) in Chinese boys.
Methods: In this study, data from boys who were referred for evaluation of PP from 2015 to 2020 at a tertiary hospital in Northern China were retrospectively analyzed.
Results: Eighty-two boys were diagnosed with PP from 2015 to 2020. Sixty-two patients (75.6%) were diagnosed with central PP (CPP), and twenty patients (24.4%) were diagnosed with peripheral PP (PPP). In the CPP group, forty-nine cases were classified as idiopathic CPP, and thirteen patients had pathogenic CPP. The top three causes of PPP were congenital adrenal hyperplasia, germ cell tumors and familial male-limited PP.
Conclusion: The etiology of PP in males is diverse. The majority of CPP cases in Chinese boys are idiopathic rather than organic.

Objective: The aim of this study was to evaluate the efficiency of a buccal spray form of vitamin D compared to single oral dose (stoss therapy) and oral drops therapy in the treatment of vitamin D deficiency.
Methods: Ninety healthy children and adolescents (3-18 years) with vitamin D deficiency [serum level of 25-hydroxyvitamin D (25(OH) D) <12 ng/mL] were randomized to receive vitamin D3 buccal spray (2000 U, n=30, group 1) for six weeks, oral drops (2000 U, n=30, group 2) for six weeks and a single oral dose (300 000 U) vitamin D3 (n=30, group 3). Serum calcium, phosphorus, alkaline phosphatase, parathyroid hormone and 25(OH)D levels of the patients were measured at baseline and after the treatment on the 42nd day.
Results: All three groups had a significant increase in serum 25(OH)D concentrations (p<0.001). In group 1, baseline mean 25(OH)D was 8.0±0.41 ng/mL, which rose to 22.1 (17.8-28.2) ng/mL after treatment with a mean increase of 15.6±1.3 ng/mL. Similarly in group 2, baseline, post-treatment and mean increase in 25(OH)D concentrations were 7.9±0.45 ng/mL, 24.4 (20.6-29.6) ng/mL and 17.3±1.1 ng/mL while for group 3 these values were 7.6±0.47 ng/mL, 40.3 (29.4-58.4) ng/mL and 34.3±3.2 ng/mL, respectively.
Conclusion: We conclude that vitamin D3 supplementation with buccal spray and oral drops is equally effective in terms of raising vitamin D concentrations in short-term treatment of vitamin D deficiency.

Objective: Monogenic diabetes is a heterogeneous disease that causes functional problems in pancreatic beta cells and hyperglycemia. The aim of this study was to determine the clinical and laboratory features, the admission characteristics and distribution of monogenic form of diabetes in childhood in Turkey.
Methods: Patients aged 0-18 years, who were molecularly diagnosed with monogenic diabetes, and consented to participate, were included in the study.
Results: Seventy-seven (45.6%) female and 92 male cases with a mean age of 8.18±5.05 years at diagnosis were included. 52.7% of the cases were diagnosed with monogenic diabetes by random blood glucose measurement. The reason for genetic analysis in 95 (56.2%) of cases was having a family member diagnosed with diabetes under the age of 25. At the time of diagnosis, ketone was detected in urine in 16.6% of the cases. Mean hemoglobin A1c on admission, fasting blood glucose, fasting insulin, and c-peptide values were 7.3±2.1%, 184.9±128.9 mg/dL, 9.4±22.9 IU/L, 1.36±1.1 and ng/L respectively. GCK-MODY was found in 100 (59.2%), HNF1A-MODY in 31 (18.3%), and variants in ABCC8 in 6 (3.6%), KCNJ11 in 5 (3%), HNF4A in 2 (1.2%), and HNF1B in 2 (1.2%).
Conclusion: Recent studies have indicated HNF1A-MODY is the most frequent of all the MODY-monogenic diabetes cases in the literature (50%), while GCK-MODY is the second most frequent (32%). In contrast to these reports, in our study, the most common form was GCKMODY while less than 20% of cases were diagnosed with HNF1A-MODY.

Objective: This preliminary review was conducted to inform the design of a new service to support families with children with Prader-Willi syndrome (PWS). Families were invited to attend a pilot clinic at a hospital outpatient department, comprising appointments with a multi-disciplinary team (MDT).
Methods: Following the clinic, families (n=6) were invited to take part in semi-structured qualitative interviews that were audio-recorded, transcribed and analysed using thematic analysis.
Results: Families reported that the clinic offered enhanced support in the following categories: integrated care; professional input; signposting to social support (respite and financial); connection with the wider PWS community; and behavioural support.
Conclusion: This is the first paper that documents the parental perspective of an MDT clinic for children with PWS. The families felt an MDT clinic was superior to current care, offering more convenient access to an enhanced service, which would provide integrated and consistent care for their children’s diverse, challenging and changing needs.

Systemic pseudohypoaldosteronism (PHA) is a rare, salt-wasting syndrome that is caused by inactivating variants in genes encoding epithelial sodium channel subunits. Hyponatremia, hyperkalemia, metabolic acidosis, increased aldosterone and renin levels are expected findings in PHA. Clinical management is challenging due to high dose oral replacement therapy. Furthermore, patients with systemic PHA require life-long therapy. Here we report a patient with systemic PHA due to SCNN1B variant whose hyponatremia and hyperkalemia was detected at the 24th hour of life. Hyperkalemia did not improve with conventional treatments and dialysis was required. He also developed myocarditis and hypertension in follow-up. Challenges for diagnosis and treatment in this patient are discussed herein. In addition, published evidence concerning common features of patients with SCNN1B variant are reviewed.

Kabuki syndrome (KS) is a disease characterized by distinctive facial features, skeletal anomalies and delay in neuromotor development. KS 1 is an autosomal dominant condition caused by mutations in the KMT2D gene, whereas KS 2 is an X-linked disorder caused by mutations in the KDM6A gene. In the majority of KS patients who present with hypoglycemia, KDM6A is the defective gene. A 9-month old girl was admitted to our emergency department due to a seizure. On physical examination, hypotonia, mild facial dysmorphism, brachydactyly of the 5th finger, prominent finger pads and pansystolic murmur were detected. A fasting glucose tolerance test was performed the next day due to her history of hypoglycemia, but she had convulsions at the fifth hour of the test. Her serum glucose was 24 mg/dL, insulin 1.94 mIU/L, C-peptide 0.94 ng/mL, growth hormone 11 ng/mL, anti-insulin antibody 4.2 IU/mL, cortisol 19.8 µg/dL, and adrenocorticotropic hormone 9.3 pg/mL. A diagnosis of hyperinsulinemic hypoglycemia was considered. Given the abnormalities, genetic analysis for congenital hyperinsulinism, including the genes causing KS was performed. A heterozygous frameshift mutation (c.2579del, p.Leu860Argfs*70) was detected in the KMT2D gene. Epilepsy and other neurological symptoms may be seen in KS patients and in some of these the neurological symptoms are the result of hypoglycemia. In such cases, the detection and prevention of hypoglycemia can help prevent the progression of neurological symptoms. We suggest considering the diagnosis of KS for patients with hypoglycemia and dysmorphic features, even if the patient does not manifest all features of KS.

Isolated growth hormone deficiency (IGHD) type 1A is a rare, autosomal recessive disorder caused by deletion of the GH1 gene and characterized by early onset severe short stature and typical phenotype. Lack of exposure to GH during fetal life often leads to formation of anti-GH antibody following exposure even the least immunogenic recombinant human GH (rhGH). Some patients with circulating anti-GH antibodies demonstrate lack of growth response to GH while others do not. However, the clinical significance of this antibody is unclear; hence testing is not routinely recommended. Three siblings, born of a consanguineous union, were referred with severe short stature. They were evaluated and IGHD was diagnosed in all of them. Genetic analysis revealed that all three had homozygous 6.7 Kb deletion in GH1 gene, while their parents displayed a pattern of heterozygous 6.7 Kb deletions. rhGH was started at 10, 6 and 1.58 years of age, respectively. Growth and hormonal parameters were monitored throughout the course of treatment. The eldest sibling demonstrated expected growth velocity (9.5 cm/year) for the first year of rhGH that rapidly waned thereafter (2.5 cm/year). The youngest sibling experienced excellent growth response even after the third year (10.3 cm/year) while the middle sibling displayed sub-optimal response from rhGH initiation (6.3 cm/year). Change of rhGH brand did not work in the two elder sisters. Such a different growth response with rhGH in three siblings harbouring similar genetic abnormality has not been described previously.

Our objective was to further expand the spectrum of clinical characteristics of the IGSF1 deficiency syndrome in affected males. These characteristic include almost universal congenital central hypothyroidism (CeH) with disharmonious pubertal development (normally timed testicular growth, but delayed rise of serum testosterone), macroorchidism, increased body mass index (BMI), and decreased attentional control. In addition, a subset of patients show prolactin deficiency, transient partial growth hormone deficiency in childhood and increased growth hormone secretion in adulthood. We present a family in which the proband was diagnosed with CeH and low serum prolactin. Severe weight gain started at two years old, with a BMI of 42.3 at 13.9 years. Testicular enlargement (5-6 mL, 3.8-4.3 standard deviation score) started aged three years. A pathogenic variant was found in the IGSF1 gene: c.3411_3412del, p.(Tyr1137*). His brother was referred for short stature at age 13 years and was diagnosed with CeH, normal serum prolactin and IGF-1, and disharmonious puberty. In four male relatives (the proband’s brother and three cousins) with the variant (one adult), free thyroxine (fT4) was below the lower limit of the reference range in two, and just above this limit in the other two. Three were overweight or obese, adolescents had disharmonious pubertal development and the adult had profound macroorchidism. In conclusion, male hemizygous carriers of a pathogenic IGSF1 variant can present with fT4 concentration above the lower limit of the reference range while severe early onset obesity or premature testicular growth are part of the phenotypic spectrum.

The current Coronavirus disease-2019 (COVID-19) pandemic has forced health care teams to look for alternative approaches to manage a great number of children with diabetes, not only in rural but also in urban locations. The aim was to assess the provision of information about follow-up of new-onset pediatric type 1 diabetes (T1D) patients, and to investigate the integration of telemedicine into routine clinical care in the long term. The changes in coefficient of variation (CV), standard deviation and percentages of time in range (TIR), time below range (TBR) and time above range were evaluated in eight children with new-onset T1D, diagnosed during the COVID-19 pandemic. The study period was two-months of follow-up using a telemedicine system. Median follow-up time was 51 (24-66) days. Two of the patients were using low glucose suspend system and six were on multiple daily injection therapy. Target TIR values were achieved in seven patients in the last televisit and, in line with recent guidelines, a TBR <70 mg/dL (<3.9 mmol/L) (level 1 hypoglycemia) of <4% and a TBR <54 mg/dL (<3.0 mmol/L) (level 2 hypoglycemia) of <1% were achieved in all patients. Seven patients achieved a CV of <36% at their last televisit. Telemedicine as an alternative follow-up tool during unusual circumstances such pandemics, even in countries where it is not routinely used, could be beneficial to achieve optimum glycemic control in patients with new-onset T1D.