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Objective: Maturity onset diabetes of the young (MODY) occurs due to mutations in genes involved in pancreatic beta cell function and insulin secretion, has heterogeneous clinical and laboratory features, and account for 1-5% of all diabetes cases. The prevalence and distribution of MODY subtypes vary between countries. The aim of this study was to evaluate the clinical and laboratory characteristics, mutation distribution, and phenotype-genotype relationship in a large case series of pediatric Turkish patients genetically diagnosed with MODY. Methods: MODY cases from 14 different pediatric endocrinology departments were included. Diagnosis, treatment, follow-up data, and results of genetic analysis were evaluated. Results: A total of 224 patients were included, of whom 101 (45%) were female, and the mean age at diagnosis was 9.4±4.1 years. Gene variant distribution was: 146 (65%) GCK; 43 (19%) HNF1A; 8 (3.6%) HNF4A, 8 (3.6%) KLF11 and 7 (3.1%) HNF1B. The remaining 12 variants were: PDX (n=1), NEUROD1 (n=3), CEL (n=1), INS (n=3), ABCC8 (n= 3) and KJNC11 (n=1). Of the cases, 197 (87.9%) were diagnosed with incidental hyperglycemia, 16 with ketosis (7%) and 7 (3%) with diabetic ketoacidosis (DKA), while 30% presented with classical symptoms of diabetes. Two-hundred (89%) had a family history of diabetes. Anti-GAD antibody was detected in 13 cases, anti-islet antibody in eight and anti-insulin antibody in four. Obesity was present in 16. Distribution of therapy was: 158 (71%) diet only; 23 (11%) intensive insulin treatment; 17 (7.6%) sulfonylureas; 10 (4.5%) metformin; and 6 (2.7%) insulin and oral anti-diabetic treatment. Conclusion: This was the largest genetically diagnosed series from Turkey. The most common gene variants were GCK and HNF1A with much lower proportions for other MODY types. Hyperglycemia was the most common presenting symptom while 11% of patients had diabetes-associated autoantibodies and 7% were obese. The majority of patients received dietary management only. [ABSTRACT FROM AUTHOR]

Objective: Noonan syndrome (NS) is characterized by dysmorphic facial features, short stature, congenital heart defects, and varying levels of developmental delays. It is a genetic, multisystem disorder with autosomal dominant inheritance and is the most common of the RASopathies. In approximately 50% of patients, NS is caused by variants in the Protein Tyrosine Phosphatase Non-Receptor Type 11 (PTPN11) gene. The aim of this study was to evaluate two patients with a previously reported PTPN11 homozygous variant for the first time and seven other kindred members carrying the same heterozygous variant in terms of clinical, biochemical, genetic, and response to treatment. Methods: Nine patients diagnosed with NS due to the same variants in the PTPN11 gene were included in the study. Results: The median (range) age at diagnosis was 11.5 (6.8-13.9) years and the mean follow-up duration was 4.7 (1-7.6) years. In eight patients (88.9%), short stature was present. The height standard deviation score of the patients on admission was -3.24±1.15. In six of the patients, growth hormone treatment was initiated. Cardiovascular or bleeding disorders were not detected in any of the patients. Three (33.3%) had hearing loss, two (22.2%) had ocular findings and one (11.1%) had a horseshoe kidney. The mean psychomotor development performance score was 84.03±17.09 and the verbal score was 82.88±9.42. Genetic analysis revealed a variant in the PTPN11 gene [c.772G>A; (p.Glu258Lys)] that had been previously described and was detected in all patients. Two patients were homozygous for this variant and short stature was more severe in these two. Conclusion: A previously described in PTPN11 affected nine members of the same kindred, two with homozygous inheritance and the remainder being heterozygous. To the best of our knowledge, these are the first homozygous PTPN11 case reports published, coming from two related consanguineous families. [ABSTRACT FROM AUTHOR]

Congenital generalized lipodystrophy (CGL) is a rare, autosomal recessive disorder characterized by an almost complete absence of body fat. In CGL, patients may have hyperphagia due to leptin deficiency. Recombinant human leptin (metreleptin) has been suggested as an effective treatment option. We present successful treatment with metreleptin in a boy with CGL and results from the first year of follow-up. An eight-month-old boy presented with excessive hair growth and a muscular appearance. On examination he had hypertrichosis, decreased subcutaneous adipose tissue over the whole body and hepatomegaly. Laboratory investigations revealed hypertriglyceridemia, hyperinsulinemia, elevated liver transaminases and low leptin levels. Molecular genetic analysis detected a homozygous, c.465_468delGACT (p. T156Rfs*8) mutation in the BSCL2 gene. A diagnosis of CGL type 2 was considered. Despite dietary intervention, exercise, and treatment with additional omega-3 and metformin, the hypertriglyceridemia, hyperinsulinemia, and elevated liver transaminase levels worsened. Metreleptin treatment was started and after one year hyperphagia had disappeared, and there was dramatic improvement in levels of insulin, hemoglobin A1c, triglycerides and liver transaminases. Hepatosteatosis was lessened and hepatosplenomegaly was much improved. Metreleptin appears to be an effective treatment option in children with CGL that remarkably improved metabolic complications in the presented case. Initiation of metreleptin treatment in the early period may decrease mortality and morbidity, and increase the quality of life in children with CGL. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Objective: To determine inequalities in access to diabetes technologies and the effect of socioeconomic factors on families with children with type 1 diabetes., Methods: In this multicenter cross-sectional study, parents of children with type 1 diabetes completed a questionnaire about household sociodemographic characteristics, latest HbA1c values, continuous glucose monitoring (CGM) and insulin pump use of children, the education and working status of parents. These characteristics were compared between technology use (only-CGM, only-pump, CGM+pump, no technology use)., Results: Among 882 families, only-CGM users, only-pump users, and CGM+pump users compared with no technology users, adjusting for age, sex, region, education levels, number of working parents, and household income. Children living in the least developed region had lower odds of having only-CGM (OR=0.20, 95%CI 0.12-0.34) and having CGM+pump (OR=0.07, 95%CI 0.03-0.22) compared with those living in the most developed region. Children with parents who had not finished high school had lower odds of having only-CGM (Mothers: OR=0.36, 95%CI 0.19-0.66; fathers: OR=0.32, 95%CI 0.18-0.60) or both CGM+pump (OR=0.27, 95%CI 0.11-0.64; fathers: OR=0.34, 95%CI 0.15-0.79) rather than no-technology compared to children whose parents has a university degree. Every $840 increase in the household income increased the odds by 5% for having only-CGM (OR=1.05, 95%CI 1.02-1.09) and CGM+pump (OR=1.05, 95%CI 1.01-1.08)., Conclusion: Socioeconomic factors such as education, regions, and income were associated with inequality in access to technologies. The inequalities are more prominent in access to CGM while CGM had a bigger contribution to glycemic control.