PHENOTYPIC, HORMONAL AND MOLECULAR GENETIC CHARACTERISTICS OF 5-ALPHA REDUCTASE TYPE 2 DEFICIENCY PATIENTS: A MULTICENTER STUDY FROM TURKEY

WOS: 00041259540526

Novel Mutations in Obesity-related Genes in Turkish Children with Non-syndromic Early Onset Severe Obesity: A Multicentre Study

Objective: Non syndromic monogenic obesity is a rare cause of early onset severe obesity in the childhood period. This form may not be distinguishable from other forms of severe obesity without genetic analysis, particularly if patients do not exibit any physical abnormalities or developmental delay. The aim of this study was to screen 41 different obesity-related genes in children with nonsyndromic early onset severe obesity. Methods: Children with severe (body mass index-standard deviation score >3) and early onset (<7 years) obesity were screened by next-generation sequencing based, targeted DNA custom panel for 41 known-obesity-related genes and the results were confirmed by Sanger technique. Results: Six novel variants were identified in five candidate genes in seven out of 105 children with severe obesity; two in SIM1 (p.W306C and p.Q36X), one in POMC (p.Y160H), one in PCSK1 (p.W130G fs Ter8), two in MC4R (p.D126E) and one in LEPR (p.Q4H). Additionally, two previously known variations in MC4R were identified in four patients (p.R165W in three, and p.V166I in one). Conclusion: We identified six novel and four previously described variants in six obesity-related genes in 11 out of 105 childrens with early onset severe obesity. The prevalence of monogenic obesity was 10.4\% in our cohort

Characteristics of Turkish children with Type 2 diabetes at onset: a multicentre, cross-sectional study

Aims To describe the baseline clinical and laboratory findings and treatment modalities of 367 children and adolescents diagnosed with Type 2 diabetes in various paediatric endocrinology centres in Turkey. Methods A standard questionnaire regarding clinical and laboratory characteristics at onset was uploaded to an online national database system. Data for 367 children (aged 6-18 years) newly diagnosed with Type 2 diabetes at 37 different paediatric endocrinology centres were analysed. Results After exclusion of the children with a BMI Z-score 50% of the children were asymptomatic at diagnosis. The other important result of our study was the high rate of exclusion from the initial registration (38%), suggesting that accurate diagnosis of Type 2 diabetes in youth is still problematic, even for paediatric endocrinologists

Characteristics of Turkish children with Type 2 diabetes at onset: a multicentre, cross-sectional study

Aims To describe the baseline clinical and laboratory findings and treatment modalities of 367 children and adolescents diagnosed with Type 2 diabetes in various paediatric endocrinology centres in Turkey. Methods A standard questionnaire regarding clinical and laboratory characteristics at onset was uploaded to an online national database system. Data for 367 children (aged 6-18 years) newly diagnosed with Type 2 diabetes at 37 different paediatric endocrinology centres were analysed. Results After exclusion of the children with a BMI Z-score < 1 SD, those with genetic syndromes associated with Type 2 diabetes, and those whose C-peptide and/or insulin levels were not available, 227 cases were included in the study. Mean age was 13.8 +/- 2.2 (range 6.5-17.8) years, with female preponderance (68\%). Family history of Type 2 diabetes was positive in 86\% of the children. The mean BMI was 31.3 +/- 6.5 kg/m(2) (range 18.7-61) and BMI Z-score was 2.4 +/- 0.8 (range 1-5). More than half (57\%) of the children were identified by an opportunistic diabetes screening due to existing risk markers without typical symptoms of diabetes. Only 13\% (n = 29) were treated solely by lifestyle modification, while 40.5\% (n = 92) were treated with metformin, 13\% (n = 30) were treated with insulin, and 33.5\% (n = 76) were treated with a combination of insulin and metformin initially. Mean HbA(1C) levels of the insulin and combination of insulin and metformin groups were 98 (11.1\%) and 102 mmol/mol (11.5\%), respectively, and also were significantly higher than the lifestyle modification only and metformin groups mean HbA(1C) levels (70(8.6\%) and 67 mmol/mol (8.3\%), respectively). Conclusions An opportunistic screening of children who are at high risk of Type 2 diabetes is essential, as our data showed that > 50\% of the children were asymptomatic at diagnosis. The other important result of our study was the high rate of exclusion from the initial registration (38\%), suggesting that accurate diagnosis of Type 2 diabetes in youth is still problematic, even for paediatric endocrinologists