Genotype of congenital adrenal hyperplasia patients with testicular adrenal rest tumor.

Testicular adrenal rest tumor (TART) is one of the important complications that can cause infertility in male patients with congenital adrenal hyperplasia (CAH) and should therefore be diagnosed and treated at an early age. The factors that result in TART in CAH have not been completely understood. The aim of this study is to evaluate the genotype-phenotype correlation in CAH patients with TART. METHOD: Among 230 malepatients with CAH who were followed upwith regular scrotal ultrasonography in 11 different centers in Turkey, 40 patients who developed TARTand whose CAH diagnosis was confirmed by genetic testing were included in this study. Different approaches and methods were used for genotype analysis in this multicenter study. A few centers first screened the patients for the ten most common mutations in CYP21A2 and performed Sanger sequencing for the remaining regions only if these prior results were inconclusive while the majority of the departments adopted Sanger sequencing for the whole coding regions and exon-intron boundaries as the primary molecular diagnostic approach for patients with either CYP21A2 orCYP11B1 deficiency. The age of CAH diagnosis and TART diagnosis, type of CAH, and identified mutations were recorded. RESULTS: TART was detected in 17.4% of the cohort [24 patients with salt-wasting (SW) type, four simple virilizing type, and one with nonclassical type with 21-hydroxylase (CYP21A2) deficiency and 11 patients with 11-beta hydroxylase (CYP11B1) deficiency]. The youngest patients with TART presenting with CYP11B1 and CYP21A2 deficiency were of 2 and 4 years, respectively. Eight different pathogenic variants in CYP21A2were identified. The most common genotypes were c.293-13C>G/c.293-13C>G (31%) followed by c.955C>T/c.955C>T(27.6%) and c.1069C>T/c.1069C>T (17.2%). Seven different pathogenic variants were identified in CYP11B1. The most common mutation in CYP11B1 in our study was c.896T>C (p.Leu299Pro). CONCLUSION: We found that 83% TART patients were affected with SW typeCYP21A2 deficiency,and the frequent mutations detected were c.955C>T (p.Gln319Ter), c.293-13C>G in CYP21A2 and c.896T>C (p.Leu299Pro) inCYP11B1. Patients with CYP11B1 deficiency may develop TART at an earlier age. This study that examined the genotype-phenotype correlation in TART may benefit further investigations in larger series.

PLXNB1 mutations in the etiology of idiopathic hypogonadotropic hypogonadism.

Idiopathic hypogonadotropic hypogonadism (IHH) comprises a group of rare genetic disorders characterized by pubertal failure caused by gonadotropin-releasing hormone (GnRH) deficiency. Genetic factors involved in semaphorin/plexin signaling have been identified in patients with IHH. PlexinB1, a member of the plexin family receptors, serves as the receptor for semaphorin 4D (Sema4D). In mice, perturbations in Sema4D/PlexinB1 signaling leads to improper GnRH development, highlighting the importance of investigating PlexinB1 mutations in IHH families. In total, 336 IHH patients (normosmic IHH, n = 293 and Kallmann syndrome, n = 43) from 290 independent families were included in the present study. Six PLXNB1 rare sequence variants (p.N361S, p.V608A, p.R636C, p.V672A, p.R1031H, and p.C1318R) are described in eight normosmic IHH patients from seven independent families. These variants were examined using bioinformatic modeling and compared to mutants reported in PLXNA1. Based on these analyses, the variant p.R1031H was assayed for alterations in cell morphology, PlexinB1 expression, and migration using a GnRH cell line and Boyden chambers. Experiments showed reduced membrane expression and impaired migration in cells expressing this variant compared to the wild-type. Our results provide clinical, genetic, molecular/cellular, and modeling evidence to implicate variants in PLXNB1 in the etiology of IHH.

Evaluation of Allergic Disease Prevalence and Related Risk Factors in Children with Autoimmune Thyroiditis.

BACKGROUND: Allergic and autoimmune diseases are caused by an impaired immunological response resulting from different types of T-helper (Th) cells. Since the Th cell production is in a certain balance, an inverse relationship between the 2 disease groups may exist. In this study, we aimed to investigate the frequency of allergic diseases in children with autoimmune thyroiditis (AT). METHODS: Symptoms of allergic diseases were investigated by the (International Study of Asthma and Allergies in Childhood) ISAAC questionnaire. The questionnaire was administered to a group of 300 children with AT and a control group of 300 children with no known autoimmune disease. The risk factors for allergic diseases and sociodemographic characteristics were investigated. A multivariable logistic regression analysis was performed with the risk factors of allergic diseases. RESULTS: Asthma, wheezing during the last year, wheezing with exercise, disease-free night cough, and night cough were significantly less common in patients with AT. Allergic rhinitis symptoms, except physician-diagnosed allergic rhinitis, are found significantly less frequently in patients with AT. It was found that the presence of AT and an increase in the number of children in the family reduce the risk of allergic diseases; cat-dog contact before 1 year of age and the presence of asthma, eczema, or allergic rhinitis in the mother increase the risk of allergic diseases. CONCLUSIONS: Asthma and allergic rhinitis symptoms were significantly less common in children with AT. AT reduces the risk of allergic diseases.

The Effects of Risk Behaviors and Orthorexic Behavior on Glycemic Control in Adolescents with Type 1 Diabetes

Objective: Adolescents with chronic disease are as likely to exhibit risk-taking behavior as their peers. The aim was to investigate the risk behaviors of adolescents with type 1 diabetes (T1D) and the effect of orthorexic eating behaviors (OEB) on glycemic control (GC). Methods: This cross-sectional study was conducted with 107 adolescents with T1D, aged between 13-18 years and attending high school. The Risk Behavior Scale (RBS) and Orthorexic Behavior Scale (ORTO-11) were administered. A high RBS score indicates risky behavior; a low ORTO-11 score suggests a tendency to OEB. Participants hemoglobin A1c (HbA1c) status was used to assess GC: optimal GC (HbA1c ≤7%); or poor GC (HbA1c >7%). Results: Among females, those with poor GC had significantly lower (p=0.031) ORTO-11 scores than those with optimal GC, which was not the case in males. A significant correlation (r=0.358, p<0.001) was found between HbA1c and total RBS, eating habits subscale, and suicidal tendency subscale scores. Participants with poor GC had significantly higher eating habits subscale, alcohol use, and tobacco use subscale scores (p<0.05). Among females, total RBS and suicidal tendency subscale score was found to be significantly higher in those with poor GC; among males, alcohol subscale score was found to be significantly higher in those with poor GC. Conclusion: This study is the first to show the effect of the tendency for OEB on GC among female adolescents with T1D. The study showed that, along with inappropriate eating behaviors, adolescents with T1D should also be assessed for other risk behaviors to help achieve optimal GC.

Effects of 5-Hydroxymethylfurfural on Pubertal Development of Female Wistar Rats

Objective: 5-Hydroxymethylfurfural (HMF) is formed when sugars are heated in the presence of amino acids. HMF is naturally present in many foods. To investigate the toxic effects of HMF on the reproductive system of peripubertal rats. Methods: In the study, 24 immature female Wistar rat were divided into three groups: control (CT) fed with no HMF; low dose fed with 750 mg/kg/day of HMF and high dose (HD) groups fed with 1500 mg/kg/day of HMF. All groups received these diets for three weeks from postnatal day (PND) 21. The vaginal opening (VO) was monitored daily and euthanasia occurred on PND 44. Gonadotropin, estradiol (E2), progesterone and anti-Müllerian hormone (AMH) concentrations were measured. Reproductive organ weights and ovarian follicle counts were compared. Results: The HD HMF group had earlier VO. Higher mean luteinising hormone (2.9±1.2 vs 1.3±0.3 mIU/mL) and mean E2 (34.7±8.8 vs 21.2±3.9 pg/mL) and lower mean AMH (2.7±0.5 vs 4.7±0.7 ng/mL) concentrations were found in the HD compared to the CT group. The HD group also had increased number of secondary atrophic follicles. Conclusion: These results indicate that peripubertal exposure to HMF at HD result in precocious puberty and decreased AMH levels in female Wistar rats.

A novel LEMD3 pathogenic variant in a son and mother with osteopoikilosis.

Elmaogullari S, Yildiz AE, Demir S, Gürkan H, Uçaktürk SA. A novel LEMD3 pathogenic variant in a son and mother with osteopoikilosis. Turk J Pediatr 2019; 61: 594-598. Osteopoikilosis (OPK) is a rare, benign condition characterized by osteosclerotic foci that occur in the epiphyses and metaphyses of long bones, wrists, feet, ankles, pelvis, and scapulae. We report a 16-year-old boy and his mother incidentally found to have sclerotic lesions on X-ray. Both of them were asymptomatic and the bone scan of the boy ruled out osteoblastic metastases. We have shown that the boy and his mother have a previously unknown pathogenic variant of the LEMD3 gene, supporting the diagnosis of osteopoikilosis.

Anxiety, depression and self-esteem levels in obese children: a case-control study.

BACKGROUND: Obesity is a global health problem affecting all age groups. Childhood obesity, which may cause chronic diseases including diabetes mellitus, cardiovascular disease and cancer, etc., deserves more attention. However, few studies highlight the association between childhood obesity and psychological diseases. In the present study, we aimed to evaluate the psychological condition in obese children. METHODS: One hundred and sixty-seven obese (body mass index (BMI) >95th percentile) and 200 normal weight children (BMI between 5th and 85th percentile) aged 9-16 years were enrolled into this case-control study. In order to assess the self-concept, anxiety and depression levels: the Piers-Harris Children's Self-Concept Scale (PHCSCS), state and trait anxiety inventory for children (STAI-C) and the children depression inventory (CDI) were administered both obese and control groups. RESULTS: There were significant differences among obese and control groups in terms of the total score of PHCSCS [55 (22-69) versus 65 (57-74)], STAI-C [37 (20-55) versus 28 (20-42)], and CDI [12 (4-39)] versus [8 (3-19)]; respectively (p<0.001, p<0.001, p<0.001). We also found statistically significant differences among groups in all of the subscales parameters of PHCSCS (p<0.001). CONCLUSIONS: Our results indicate that obese children may experience psychiatric disorders more than normal-weight peers.