Search

3 M syndrome is a well-known autosomal recessive skeletal genetic disorder caused by biallelic pathogenic variants in the CUL7, OBSL1, and CCDC8 genes. Affected individuals exhibit profound pre- and postnatal growth retardation, distinctive facial features with normal intelligence. This study aims to provide insight into the comprehensive evaluation of clinical, laboratory, and radiological findings, expand the mutational spectrum of the disease, and establish a genotype–phenotype correlation in the present cases. A total of 25 patients from 19 unrelated families were included in the study. Genetic etiology was determined in probands through the utilization of Sanger sequencing and/or targeted gene panel analysis. The clinical, laboratory, and genetic features of all patients at admission and during follow-up were documented. Genotype–phenotype correlation was carried out in the CUL7 and OBSL1 groups. The genetic etiology was established in all patients (n = 25/25, 100%). We identified 15 distinct variants in CUL7, OBSL1, and CCDC8 genes, with eleven being novel. CUL7 variants were present in 13 patients (n = 13/25, 52%), while OBSL1 variants were found in 11 patients (n = 11/25, 44%). No notable distinctions were found in mean birth weight, height, and standard deviation scores between the CUL7 and OBSL1 mutation groups (p > 0.05). Patients with CUL7 variants exhibited significantly lower height standard deviation scores both at admission and at the last examination, as well as lower weight standard deviation scores at the last examination, compared to those with OBSL1 variants (p < 0.05). Conclusion: To date, genotype–phenotype correlations have been identified in a limited number of studies. Further research involving larger cohorts is necessary to solidify these correlations. What is Known: • 3M syndrome is a well-known skeletal dysplasia caused by biallelic pathogenic variants in CUL7, OBSL1, and CCDC8 genes. • Despite genetic heterogeneity, clinical, and radiologic features show homogeneity in affected individuals. What is New: • Genotype-phenotype correlations have been established in limited studies. • The CUL7 group exhibited significantly lower height SDS at both admission and the final evaluation and lower weight SDS at the final examination compared to the OBSL1 group. • The frequency of variants in the OBSL1 gene among Turkish patients exceeds the rates reported in the literature. • Gradenigo syndrome is being reported for the first time in a patient with 3M syndrome. [ABSTRACT FROM AUTHOR]

Objective: Polycystic ovary syndrome (PCOS) is a heterogeneous, systemic disease that occurs under the influence of genetic and environmental factors, clinically characterized by hyperandrogenism, menstrual irregularity and chronic anovulation, often starting in adolescence and seen in 6-20% of women of reproductive age. In this study, it was aimed to determine the clinical features of cases diagnosed with PCOS and to evaluate the relationship of PCOS with obesity and insulin resistance. Material and Method: Clinical, laboratory and radiological data of 52 cases diagnosed with PCOS were retrospectively evaluated by scanning patient files. Results: Average age of 52 patients was 16.12±1.21 years, body mass index (BMI); 26.67± 5.69 kg/m2, mean BMI SDS was found to be 1.41±1.47. The mean FGS was 10.77 ±3.64 and the FG score of 32 cases (61.5%) was found to be above 8. Total testosterone was found to be above 50 ng/dl in 48 cases (92.3%). BMI SDS and ALT, sex hormone binding globulin (SHBG) levels were found to be statistically significantly different in the insulin resistant group (p =0.001, p =0.031, p =0.005, respectively). Overweight and obese subjects (group1) were compared with normal weight and underweight subjects (group2). While HOMA-IR, ALT, triglyceride and total cholesterol were significantly higher in Group1, LH, LH/FSH ratio, estradiol (E2) and SHBG levels were significantly higher in Group2. Conclusion: Insulin resistance and obesity were absent in approximately half of the adolescent PCOS cases. Low SHBG levels were found to be associated with insulin resistance, obesity and hirsutism. In our study, SHBG levels were found to be significantly lower in group 1 when compared to overweight and obese subjects (group1) and normal weight and underweight subjects (group2). Although insulin resistance and obesity are not necessary criteria for the diagnosis of adolescent PCOS, they may have roles in the pathogenesis of PCOS. Obesity and insulin resistance may lead to hyperandrogenism by decreasing SHBG levels and increasing free androgens. [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: Type 1 diabetes mellitus (T1D); It is a chronic disease that can cause micro and macrovascular complications. Fetuin A synthesized in hepatocytes is a marker of vascular diseases. The production of this glycoprotein increases with hyperlipidemia and hyperglycemia. In our study, we aimed to determine the relationship between the factors affecting Fetuin A level and metabolic status and complications in children and adolescents with T1D. Methods: Children with a diagnosis of T1D of at least 3 years and healthy people of similar age and gender were included in our study. The subjects were divided into subgroups as metabolic control according to their HbA1c levels in the last one year, and statistical analyzes were performed in comparison with healthy controls. Results: The study consisted of 111 subjects, 74 (37 females) with T1D and 37 healthy controls (19 females). The mean age of the cases with T1D was 15.03±3.03 years, and 14.58±2.72 years in the healthy control group. Sex, BMI, height SDS, body weight SDS and puberty stages were statistically similar between the patient and control groups (p>0.05). Fetuin A levels of patients with type 1 diabetes were significantly higher than the healthy control group (p<0.001). There was no statistical difference between the good, moderate and bad metabolically controlled T1D subgroups in terms of Fetuin A levels (p>0.05). However, the Fetuin A averages of the three groups formed separately from the metabolic control were statistically higher than the Fetuin A averages of the control group (p<0.001). There was no significant difference between Fetuin A levels of T1D patients with and without complications (p>0.05). There was no significant difference between Fetuin A levels of cases with T1D and those with and without overweight (p=0.422). When T1D patients were compared according to dyslipidemia/hepatosteatosis status, no significant difference was found between Fetuin-A levels (p>0.05). Discussion and Conclusion: Fetuin A levels of the patients with T1D were significantly higher in the healthy control group (p<0.001), whereas the Fetuin A levels of the groups formed compared to the metabolic control were not statistically different (p>0.05). In conclusion; The number of articles about Fetuin A in children with T1D is few in the literature. More studies are needed to evaluate the association of Fetuin A with poor control and complications in children with T1D. [ABSTRACT FROM AUTHOR]

Objective: The incidence of type 1 diabetes mellitus (T1D) in children has an increasing trend globally, with a variable rate depending on region and ethnicity. Our group first reported T1D incidence in Diyarbakır in 2011. The aim of this study was to evaluate the current incidence rate of pediatric T1D in Diyarbakır, and compare the incidence, and clinical and presenting characteristics of more recent cases with those reported in our first report. Methods: Hospital records of patients diagnosed with T1D in Diyarbakır city between 1st January 2020 and 31st December 2020 and aged under 18 years old were retrieved, and their medical data was extracted. Demographic population data were obtained from address-based census records of the Turkish Statistical Institution (TSI). Results: Fifty-seven children and adolescents were diagnosed with T1D. Of those, 34 were female (59.6%), indicating a male/female ratio of 1.47. The mean age at diagnosis was 9.5±3.9 years (0.8-17.9). TSI data indicated a population count of 709,803 for the 0-18 years age group. Thus the T1D incidence was 8.03/105 in the 0-18 age group and was higher in the 0-14 age group at 9.14/105. The cumulative increase in the incidence of T1D in the 0-14 age group was 26.9% suggesting an increasing rate of 2.7% per year. The frequency of presentation with diabetic ketoacidosis was 64.9%. Conclusion: The annual incidence of pediatric T1D in Diyarbakır city increased from 7.2/105 to 9.14/105 within the last decade. The rate of annual increase was 2.7% in the 0-14 age group comparing this study with our earlier report, with a predominance in male subjects and a shift of peak incidence from the 5-9 year age group in the first study to the 10-14 year age group in this one. [ABSTRACT FROM AUTHOR]

Objective: We aimed to evaluate the clinical, radiological and pathological findings of children and adolescents with thyroid nodules. Methods: Data of 121 children and adolescent with thyroid nodules and had fine needle aspiration (FNA) were examined retrospectively. Concomitant thyroid disease, ultrasonography (US) features of the nodule, FNA and histopathological results were recorded. FNA results were assessed according to The Bethesda System for Reporting Thyroid Cytopathology (TBSRTC). Results: Median (range) age of the cases was 14 (3-18) years and 81% were female. FNA results of patients were: insufficient in 1 (0.8%); benign in 68 (56.2%); indeterminate in 44 (36.4%); and malignant in 8 (6.6%) patients. Among 39 patients who underwent surgery, 10 (25.6%) had differentiated thyroid cancer (DTC) and the overall malignancy rate was 10.0% (10/100). Follow-up FNA results showed progress based on TBSRTC in 18.7% of benign results and 4/75 patients had DTC on surgical excision. Two of 22 patients with atypia of undetermined significance (AUS) who continued follow-up was diagnosed with DTC. Male gender, presence of Hashimoto thyroiditis and US findings of uninodularity, hypoechogenicity, increased blood flow, irregular margins, solid structure, microcalcification and presence of abnormal cervical lymph nodes were associated with malignancy. Conclusion: In this study 10% of thyroid nodules were malignant in children and adolescents. Patients with AUS have a 9% potential for malignancy. Patients with initially benign FNA result may have changes on repeat FNA when assessed with TBSTRC indicating a 5.3% false negative rate. [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]

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: 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]

Androgens play a pivotal role in non-reproductive organs such as the kidney, heart, liver, and pancreas. As androgen receptors are expressed in pancreatic and liver cells, excess testosterone can result in hypersecretion of insulin and fetuin-A, a protein produced in the liver. The expression of fetuin-A, a natural inhibitor of tyrosine kinase activity in muscle and liver, leads to insulin resistance. In addition, insulin and fetuin-A levels are thought to be affected by drugs such as glucocorticoids (GCs) and fludrocortisone. However, whether fetuin-A and insulin levels are affected by androgens and GCs in patients with classic congenital adrenal hyperplasia (CAH) is unknown. This cross-sectional study included 56 CAH patients and 70 controls. Analyses were stratified by sex and prepubertal/pubertal status to control for potential changes in serum metabolic/inflammatory markers associated with the production of sex steroids. Fasting blood glucose, insulin, triglyceride, total cholesterol, high density lipoprotein-cholesterol, aspartate aminotransferase, alanine aminotransferase, fetuin-A, and high-sensitivity C-reactive protein (hs-CRP) levels were measured in blood samples. In addition, 17α-hydroxyprogesterone, androstenedione, total testosterone, free testosterone, and dehydroepiandrosterone sulfate levels were measured before medication was administered. Insulin and fetuin-A levels were significantly higher in CAH patients than in controls. The unfavourably high levels of these substances exhibited a positive correlation with total and free testosterone. Regression analysis revealed that fetuin-A and free testosterone were the only independent predictors of the insulin level, while insulin and free testosterone levels significantly predicted the fetuin-A level (R2= 42.7% and 59.8%). Differences were also observed in triglyceride and hs-CRP levels between the pubertal and prepubertal groups. We conclude that serum fetuin-A and insulin levels may be associated with androgens in CAH patients. [ABSTRACT FROM AUTHOR]

Aims. To evaluate responsibility sharing between parents of children with type 1 diabetes and change in their occupational status one year after the diagnosis. Methods. In this cross-sectional multicenter study, parents of children under the age of 18 with a diagnosis of type 1 diabetes answered a questionnaire assessing diabetes-related responsibility sharing between parents, and occupational changes due to child's diabetes. Changes in the occupational status with associated factors and distribution of diabetes-related responsibilities between parents were analyzed. Results. Among parents of 882 children (mean (SD) age at diagnosis was 7 (3.8) years, female 52.5%), unemployment increased significantly in mothers (59.0% vs. 67.1%; p < 0.001), but not in fathers (10.4% vs. 10.7%; p > 0.05) within 1 year after their child's diagnosis. Working mother's occupational withdrawal was associated with the child's age at diagnosis (OR = 0.92, [95% CI 0.86–0.99]; p = 0.02) and mother's education (compared to a university degree or above, high school graduate (OR = 2.93, [95% CI 1.59–5.4]; p < 0.001) and not graduated high school (OR = 8.4, [95% CI 3.56–19.83]; p < 0.001)). According to the mothers, none of the responsibilities in diabetes care were shared equally between parents, while fathers reported most responsibilities were shared equally. Compared to mothers who preserved their occupation after the diagnosis, mothers who quit their occupation had significantly higher responsibility scores (2.04 vs. 1.55; p = 0.04), especially in diabetes care at school (p < 0.01). Conclusions. The difference in parents' perceptions of their involvement in their child's diabetes is remarkable. Gender differences in the child's diabetes care extend to the occupational life of parents unequally. [ABSTRACT FROM AUTHOR]