Clinical features, diagnosis and treatment outcomes of Cushing's disease in children: A multicenter study.

OBJECTIVE: Since Cushing's disease (CD) is less common in the paediatric age group than in adults, data on this subject are relatively limited in children. Herein, we aim to share the clinical, diagnostic and therapeutic features of paediatric CD cases. DESIGN: National, multicenter and retrospective study. PATIENTS: All centres were asked to complete a form including questions regarding initial complaints, physical examination findings, diagnostic tests, treatment modalities and follow-up data of the children with CD between December 2015 and March 2017. MEASUREMENTS: Diagnostic tests of CD and tumour size. RESULTS: Thirty-four patients (M:F = 16:18) from 15 tertiary centres were enroled. The most frequent complaint and physical examination finding were rapid weight gain, and round face with plethora, respectively. Late-night serum cortisol level was the most sensitive test for the diagnosis of hypercortisolism and morning adrenocorticotropic hormone (ACTH) level to demonstrate the pituitary origin (100% and 96.8%, respectively). Adenoma was detected on magnetic resonance imaging (MRI) in 70.5% of the patients. Transsphenoidal adenomectomy (TSA) was the most preferred treatment (78.1%). At follow-up, 6 (24%) of the patients who underwent TSA were reoperated due to recurrence or surgical failure. CONCLUSIONS: Herein, national data of the clinical experience on paediatric CD have been presented. Our findings highlight that presenting complaints may be subtle in children, the sensitivities of the diagnostic tests are very variable and require a careful interpretation, and MRI fails to detect adenoma in approximately one-third of cases. Finally, clinicians should be aware of the recurrence of the disease during the follow-up after surgery.

Type 1 Diabetes Incidence Trends in a Cohort of Turkish Children and Youth.

OBJECTIVE: The aim was to analyze the incidence trend and annual average incidence change of type 1 diabetes (T1DM) in the population <18 years of age in Malatya province. MATERIALS AND METHODS: Medical files of patients followed up with T1DM in pediatric endocri- nology clinics were reviewed. The data for the child census was taken from the Turkish Statistical Institute (TUIK), and T1DM incidence was analyzed according to the calendar year, gender, and age groups. Recently diagnosed T1DM patients per 100 000 children per year were calculated. In addition, the trend in annual incidence change over the period 2007-2019 was analyzed. RESULTS: The mean incidence of T1DM during the 13 years was 13.1/105 child years (13.8/105 child years for girls and 12.4/105 child years for boys). During the 13-year follow-up period, a sig- nificant increasing trend in the incidence of T1DM was detected. The average annual percent change (AAPC) was 8.3%. According to age groups, the average AAPC was 8.1% between 0 and 4 years old, 9.4% between 5 and 9 years old, 12.1% between 10 and 14 years old, and 30.1% between 15 and 17 years old. CONCLUSION: The incidence of T1DM in children under 18 years of age in Malatya, one of the larg- est cities in the Eastern Anatolia region of Turkey, was determined as 13.1/105 child years in the last 13 years and the average annual increase rate was 8.3%.

Prevalence and Predictive Clinical Characteristics of Metabolically Healthy Obesity in Obese Children and Adolescents.

BACKGROUND: The increasing prevalence of childhood obesity and accompanying comorbidities all over the world constitutes one of the most important public health problems of the changing world. The frequency and causes of the metabolically healthy obesity (MHO) phenotype in children is not clear. OBJECTIVE: The objective is to determine the prevalence of the MHO phenotype in obese Turkish children and adolescents and to identify clinical and biochemical indicators for this phenotype. METHODS: Eight hundred forty-seven obese children and adolescents, aged 3-18 years with BMI-SDS >+2 SD from the obesity outpatient clinic were included. Demographic, anthropometric, and physical examination information was collected from patient medical files. In addition, obesity-related comorbidities and results of laboratory tests were obtained. For study purposes, obese patients with no cardiometabolic risk factors were accepted as MHO, and those with ≥1 cardiometabolic risk factor were considered metabolically unhealthy obese (MUO). MHO was defined according to Damanhoury's criteria. RESULTS: Out of 847 children (mean age 10.6±3.4 years) who met the study criteria, 289 (34.1%) were diagnosed with MHO. Being younger, prepubertal, having relatively low BMI, low waist/hip ratio, low insulin resistance (HOMA-IR) index, high high-density lipoprotein, low triglyceride, low fasting insulin and glucose levels, low uric acid and low alanine transaminase (ALT) levels were associated with MHO. CONCLUSIONS: The MHO phenotype was present in just over a third of this obese pediatric cohort. The most important factors associated with MHO; age, waist-hip ratio, and BMI were determined.

Presentation, Diagnosis, and Follow-Up Characteristics of 17α-Hydroxylase Deficiency Cases with Exon 1-6 Deletion (Founder Mutation) in the CYP17A1Gene: 20-Year Single-Center Experience.

CONTEXT: 17α-Hydroxylase/17,20-lyase deficiency (17OHD) is characterized by decreased sex steroids and cortisol synthesis, as well as an increased mineralocorticoid effect. AIM: This study aimed to evaluate the clinical, biochemical, and molecular characteristics of patients with 17OHD and to discuss the diagnosis, treatment, and follow-up process. METHODS: Age, symptoms, anthropometric measurements, blood pressure, and hormonal, biochemical, and chromosomal analysis results of 13 patients diagnosed with 17OHD between 2003 and 2022 were recorded at admission and during follow-up. Whole gene next-generation sequencing was performed for the CYP17A1 gene. Multiplex ligation-dependent probe amplification was used to detect deletions in patients without point mutations in CYP17A1. RESULTS: The median age at diagnosis was 14.0 (3.5-16.8) years. Nine of 13 patients (69.2%) had 46,XY karyotypes. All patients were phenotypically female and were raised as girls. The most common reasons for admission were the absence of puberty and amenorrhea (n = 8, 61.5%), followed by hypertension (n = 3, 23.0%), and family screening (n = 2, 15.3%). At the time of diagnosis, hypertension was detected in 10 (76.9%) patients, and 11 (84.6%) patients had hypokalemia. CONCLUSIONS: 17OHD should be considered in patients with pubertal delay/primary amenorrhea, hypertension, and hypokalemia. Adrenal function should be included in the clinical study of hypergonadotropic hypogonadism, after excluding Turner syndrome, in all 46,XX females. Deletion in the CYP17A1 gene, including exons 1-6, is the founder mutation for Turkey's east and southeast regions.

Chronic Disease Management of Children Followed with Type 1 Diabetes Mellitus

Objective: With the diagnosis of chronic illness in children, a stressful period is likely to begin for both the affected child and their families. The aim of this study was to investigate the factors affecting chronic disease management by the parents of children diagnosed with type 1 diabetes mellitus (T1DM). Methods: The sample consisted of 110 children, aged between 4-17 years and their mothers. The patients had been diagnosed with T1DM for at least one year, and had attended pediatric endocrinology outpatients or were hospitalized in a single center. First, sociodemographic information about the child with T1DM were obtained. Then, the "Family Management Measure" (FaMM) was applied. The FaMM is constructed to measure family functioning and management in families who have a child with a chronic illness. Results: Paternal years of education (p=0.036), family income (p=0.008), insulin pump use (p=0.011), and time elapsed after diagnosis (p=0.048) positively affected both the management of T1DM and the child's daily life. However, presence of chronic diseases in addition to T1DM (p=0.004) negatively affected diabetes management. Higher maternal education year (p=0.013) and family income level (p=0.001) increased parental mutuality scores. However, as the time after diagnosis increased, parental mutuality scores decreased. Conclusion: It is important to evaluate the child with chronic disease with a biopsychosocial approach. This approach aims to evaluate the problems of the child and his/her family who experience the disease with a holistic approach.

Clinical Characteristics and Genetic Analyses of Patients with Idiopathic Hypogonadotropic Hypogonadism

Objective: Idiopathic hypogonadotropic hypogonadism (IHH) is classified into two groups-Kalman syndrome and normosmic IHH (nIHH). Half of all cases can be explained by mutations in >50 genes. Targeted gene panel testing with nexrt generation sequencing (NGS) is required for patients without typical phenotypic findings. The aim was to determine the genetic etiologies of patients with IHH using NGS, including 54 IHH-associated genes, and to present protein homology modeling and protein stability analyzes of the detected variations. Methods: Clinical and demographic data of 16 patients (eight female), aged between 11.6-17.8 years, from different families were assessed. All patients were followed up for a diagnosis of nIHH, had normal cranial imaging, were without anterior pituitary hormone deficiency other than gonadotropins, had no sex chromosome anomaly, had no additional disease, and underwent genetic analysis with NGS between the years 2008-2021. Rare variants were classified according to the variant interpretation framework of the American College of Medical Genetics and Genomics (ACMG)/Association for Molecular Pathology. Changes in protein structure caused by variations were modeled using RoseTTAFold and changes in protein stability resulting from variation were analyzed. Results: Half of the 16 had no detectable variation. Three (18.75%) had a homozygous (pathogenic) variant in the GNRHR gene, one (6.25%) had a compound heterozygous [likely pathogenic-variants of uncertain significance (VUS)] variant in PROK2 and four (25%) each had a heterozygous (VUS) variant in HESX1, FGF8, FLRT3 and DMXL2. Protein models showed that variants interpreted as VUS according to ACMG could account for the clinical IHH. Conclusion: The frequency of variation detection was similar to the literature. Modelling showed that the variant in five different genes, interpreted as VUS according to ACMG, could explain the clinical IHH.

Liraglutide Treatment in a Morbidly Obese Adolescent with a MC4R Gene Variant: Side Effects Reduce Success

Variants of the melanocortin-4 receptor (MC4R) gene are the most common cause of monogenic obesity. It has been shown that, while obesity cannot be controlled with diet and exercise, glucagon-like-peptide-1 receptor agonists (GLP-1 RA) provide weight loss in the short term. In this paper, our experience with liraglutide treatment in an adolescent patient carrying a MC4R gene variant is presented. A female patient was admitted first at the age of 12.5 years with a complaint of progressive weight gain. She had marked excess of appetite since infancy. On physical examination of the pubertal female patient with a body mass index (BMI) of 36.1 kg/m2 (3.48 standard deviation score), there was no pathological finding except diffuse acanthosis nigricans. Laboratory examinations revealed only insulin resistance. Weight loss was not achieved with lifestyle changes, metformin and orlistat treatments. On genetic examination, a sporadic heterozygous c.206T>G(p.I69R) variant that had been reported previously, was found in MC4R gene. Treatment with the GLP-1 RA, liraglutide, was initiated and a 19.2% reduction was achieved in the body weight and BMI at the end of 32 weeks. However, the patient, whose treatment compliance was disrupted due to significant gastrointestinal complaints, returned to her former weight within a few months (13 weeks) after treatment was stopped. In this case with a known pathogenic variant in MC4R gene, decrease of appetite and weight loss were achieved with liraglutide treatment, but side-effects of this treatment led to discontinuation of therapy. In such cases, there is need for effective and tolerable treatment options.

The Frequency of Subclinical Hypothyroidism in Obese Children and Adolescents and Its Relationship with Metabolic Parameters and Atherogenic Index.

OBJECTIVE: The effect of subclinical hypothyroidism on glucose and lipid metabolism in obese children is controversial. This study aims to compare cardiovascular risk factors in obese patients with or without subclinical hypothyroidism and determine the frequency of subclinical hypothyroidism in obese children and adolescents. MATERIALS AND METHODS: A total of 1130 obese children and adolescents aged 6-18 years were included in this single-center cross-sectional study. Metabolic parameters such as thyrotropin, free thyroxine, free triiodothyronine, homeostasis model assessment for insulin resistance, atherogenic index, and lipids were evaluated. The patients were divided into two groups-subclinical hypothyroidism group (free thyroxine normal, thyroid-stimulating hormone 5.5-10 mIU/L) (n = 59) and the control group (free thyroxine normal, thyroid-stimulating hormone < 5 mIU/L) (n = 1071). RESULTS: Subclinical hypothyroidism was detected in 59 (5.2%) of 1130 patients. The mean body mass index was similar in both groups. The mean serum insulin, homeostasis model assessment for insulin resistance, triglyceride, atherogenic index of plasma, aspartate aminotransferase, and alanine aminotransferase levels were higher in the subclinical hypothyroidism group, and the mean high-density lipoprotein cholesterol level was lower than the control group (P = .005, P < .001, P = .028, P < .001, P = .001, P < .001, and P = .018, respectively). While a positive correlation was observed between the thyroid-stimulating hormone levels and insulin, homeostasis model assessment for insulin resistance, alanine aminotransferase, triglyceride, and basal cortisol levels, a negative correlation was found between thyroid-stimulating hormone and highdensity lipoprotein cholesterol. CONCLUSION: Subclinical hypothyroidism can negatively affect the lipid and glucose profile.

Trend in initial presenting features of type 1 diabetes mellitus over a 24 year period in Turkey: a retrospective analysis of 814 cases.

BACKGROUND: The study aim was to examine changes in trends of presenting features during the diagnosis of patients followed up with newly diagnosed Type 1 diabetes mellitus (T1DM) over the past 24 years. METHODS: The study was retrospective. Patients with a diagnosis of T1D between the years of 1996-2019 were included. Patients diagnosed in the first half of the period comprised Period I, and those from the second half comprised Period II. Patient data were extracted from medical records and included gender distribution, year of diagnosis, age at diagnosis, duration of symptoms, type of admission, frequency of diabetic ketoacidosis (DKA) and biochemical parameters. Subsequently, temporal changes in trends of these parameters were sought. RESULTS: For the whole cohort the gender distribution was equal; 404 (49.6%) were girls and 410 (50.4%) were boys. Mean age at diagnosis was 8.5±4.2 years and age groupings at presentation were: 23.2% (n = 189) aged 0-4; 39.2% (n = 319) aged 5-9; 27.5% (n = 224) aged 10-13; 10.1% (n= 82) aged 14-18. At presentation 72 (12.7%) had hyperglycemia, 230 (40.6%) had diabetic ketosis, and 264 (46.6%) had DKA. In those with DKA, mild DKA was found in 103 (39.0%), moderate DKA in 81 (30.6%), and severe DKA in 80 (30.3%). While the frequency of DKA was 54.9% between 1996 and 2007 (Period I), this significantly decreased to 44.4% between 2008 and 2019 (Period II). Girls and boys had a similar rate of T1DM, and this did not change over time. Three peak ages of diagnosis were evident; 5-7, 8-10, 12-14 years of age. CONCLUSIONS: The frequency of DKA decreased and the frequency of admission with hyperglycemia and ketosis increased during the study period, which may have repercussions for mortality and morbidity rates and aid in improved treatment outcomes.

Prevalence of type 2 diabetes mellitus, metabolic syndrome, and related morbidities in overweight and obese children.

OBJECTIVES: The aim of the study was to determine the prevalence of metabolic syndrome (MetS), type 2 diabetes mellitus (T2DM), and other comorbidities in overweight and obese children in Malatya, Turkey. METHODS: Retrospective cross-sectional study. We studied 860 obese and overweight children and adolescents (obese children Body mass index (BMI) >95th percentile, overweight children BMI >85th percentile) aged between 6 and 18 years. The diagnosis of MetS, impaired glucose tolerance (IGT), impaired fasting glucose (IFG), and T2DM were defined according to modified the World Health Organization criteria adapted for children. Other comorbidities were studied. RESULTS: Subjects (n=860) consisted of 113 overweight and 747 obese children of whom 434 (50.5%) were girls. MetS was significantly more prevalent in obese than overweight children (43.8 vs. 2.7%, p<0.001), and in pubertal than prepubertal children (41.1 vs. 31.7%, p<0.001). Mean homeostasis model assessment for insulin ratio (HOMA-IR) was 3.6 ± 2.0 in the prepubertal and 4.9 ± 2.4 in pubertal children (p<0.001). All cases underwent oral glucose tolerance test and IGT, IFG, and T2DM were diagnosed in 124 (14.4%), 19 (2.2%), and 32 (3.7%) cases, respectively. Insulin resistance (IR) was present in 606 cases (70.5%). CONCLUSIONS: Puberty and obesity are important risk factors for MetS, T2DM, and IR. The prevalence of MetS, T2DM, and other morbidities was high in the study cohort. Obese children and adolescents should be carefully screened for T2DM, insulin resistance, hyperinsulinism, dyslipidemia, hypertension, IGT, and IFG. The prevention, early recognition, and treatment of obesity are essential to avoid associated morbidities.

Genomic analysis to screen potential genes and mutations in children with non-syndromic early onset severe obesity: a multicentre study in Turkey.

BACKGROUND: Obesity is a complex genetic-based pediatric disorder which triggers life-threatening conditions. Therefore, the understanding the molecular mechanisms of obesity has been a significant approach in medicine. Computational methods allow rapid and comprehensive pathway analysis, which is important for generation of diagnosis and treatment of obesity. METHODS AND RESULTS: Aims of our study are to comprehensively investigate genetic characteristics of obesity in children with non-syndromic, early-onset (< 7 years), and severe obesity (BMI-SDS > 3) through computational approaches. First, the mutational analyses of 41 of obesity-related genes in 126 children with non-syndromic early-onset severe obesity and 76 healthy non-obese controls were performed using the next generation sequencing (NGS) technique, and the NGS data analyzed by using bioinformatics methods. Then, the relationship between pathogenic variants and anthropometric/biochemical parameters was further evaluated. Obtained results demonstrated that the 15 genes (ADIPOQ, ADRB2, ADRB3, IRS1, LEPR, NPY, POMC, PPARG, PPARGC1A, PPARGC1B, PTPN1, SLC22A1, SLC2A4, SREBF1 and UCP1) which directly related to obesity found linked together via biological pathways and/or functions. Among these genes, IRS1, PPARGC1A, and SLC2A4 stand out as the most central ones. Furthermore, 12 of non-synonymous pathogenic variants, including six novels, were detected on ADIPOQ (G90S and D242G), ADRB2 (V87M), PPARGC1A (E680G, A477T, and R656H), UCP1 (Q44R), and IRS1 (R302Q, R301H, R301C, H250P, and H250N) genes. CONCLUSION: We propose that 12 of non-synonymous pathogenic variations detected on ADIPOQ, ADRB2, PPARGC1A, UCP1, and IRS1 genes might have a cumulative effect on the development and progression of obesity.

46,XY Sex Development Defect due to a Novel Homozygous (Splice Site) c.673_1G>C Variation in the HSD17B3 Gene: Case Report

The enzyme 17-ß-hydroxysteroid dehydrogenase type 3 (17ß-HSD3) catalyzes the biosynthesis of testosterone (T) from Δ4-androstenedione, and plays an important role in the final steps of androgen synthesis. 17ß-HSD3 deficiency originates from mutations in the HSD17B gene, causing an autosomal recessive 46,XY sex developmental disorder (DSD). Patients with 46,XY karyotype can exhibit a wide phenotypic spectrum, varying from complete external female genitalia to male genitalia with hypospadias. Here we report a case of 17ß-HSD3 deficiency diagnosed in the infantile period who was later found to have a novel HSD17B3 gene variation. The 14-month old patient, who exhibited a female phenotype, presented with a bilateral lump in the inguinal area. Imaging revealed bilateral testicular gonads in the inguinal area. Hormonal evaluation showed low levels of basal and stimulated serum T, a high level of androstenedione (A), and a low T/A ratio. Chromosomal analysis showed 46,XY karyotype. Sequence analysis of the HSD17B3 gene revealed a c.673_1G>C homozygous class 2 (splice site) variation in intron 9. The consanguineous parents were sequenced, and both were heterozygous for the same mutation. This variation has not been previously reported in the literature. In conclusion, a 46,XY DSD should be considered in patients with a female phenotype who exhibit gonad(s) in the inguinal area at an early age. Furthermore, in patients with insufficient T synthesis and high levels of androstenedione, 17ß-HSD3 should be considered, and molecular analysis should be done for a definitive diagnosis and subsequent genetic counseling.

TSHRV656F Activating Variant of the Thyroid Stimulating Hormone Receptor Gene in Neonatal Onset Hyperthyroidism: A Case Review

An activating variant of the thyroid stimulating hormone receptor (TSHR) gene is one of the rare causes of neonatal hyperthyroidism. This disorder may occur as a result of an autosomal dominant inheritance or sporadically through de novo variation. Here we present a case of neonatal onset congenital non-autoimmune hyperthyroidism (NAH) with a sporadic germline activating TSHRV656F variant. A female infant with tachycardia, who was transferred due to hyperthyroidism in the first week of life, displayed no other symptoms or signs. The patient's mother did not have Graves' disease, and TSHR stimulating antibodies were not present in the mother or baby. Imaging showed thyroid gland hyperplasia and left ventricular hypertrophy, the patient was subsequently put on methimazole treatment. After six months undergoing treatment, a heterozygous p.Val656Phe (V656F) (c.1966G>T) variant was detected on exon 10 of the TSHR gene. The variant was not identified in the mother and father, so the case was assumed to be sporadic. In conclusion, although the literature describes V656F variant as a somatic variant in children and adults with toxic thyroid nodule(s) that results in the structural activation of the TSH receptor, no previous cases of neonatal hyperthyroidism due to TSHRV656F variant have been reported. This study is the first case review that highlights the relationship between TSHRV656F variant and neonatal onset NAH.

Diagnostic Value of Bilateral Petrosal Sinus Sampling in Children with Cushing Disease: A Multi-center Study

Objective: Although the sensitivity and specificity of bilateral inferior petrosal sinus sampling (BIPSS) were shown to be quite high in adult patients, pediatric studies are limited in number and have conflicting results, since BIPSS is much less commonly performed in children. The aim of this study was to assess the role of BIPSS in the detection and accuracy of lateralization of pituitary adenomas in pediatric patients with Cushing disease (CD) and its possible advantage over other diagnostic methods. Methods: This was a multicenter, nationwide, web-based study. The diagnostic value of BIPSS in 16 patients, aged between four and 16.5 years with a confirmed diagnosis of CD, was evaluated retrospectively. The sensitivity and specificity of BIPSS and magnetic resonance imaging (MRI) were calculated, and compared statistically. Results: Standard tests, except for morning cortisol level, were effective in proving the presence of Cushing syndrome. While MRI findings were consistent with microadenoma in eight cases (50%), CD presence and lateralization was successfully predicted in 14 of 16 patients using BIPSS. BIPSS compared with MRI examination was significantly more accurate, both in pre-stimulation and post-stimulation results (p=0.047 and p=0.041, respectively). BIPSS showed a significantly higher sensitivity (92.8%) than MRI in detecting the pituitary source of adrenocorticotropic hormone secretion. Conclusion: These results suggest that BIPSS is superior to MRI for diagnostic work-up to confirm the diagnosis of CD. Moreover, in line with previous studies, BIPSS was shown to provide better information about adenoma location, which is vital for possible surgical intervention.

Pediatric Primary Adrenal Insufficiency: A 21-year Single Center Experience

Objective: Primary adrenal insufficiency (PAI) is a rare but potentially life-threatening condition. In childhood, PAI is usually caused by monogenic diseases. Although congenital adrenal hyperplasia (CAH) is the most common cause of childhood PAI, numerous non-CAH genetic causes have also been identified. Methods: Patients aged 0-18 years and diagnosed with PAI between 1998 and 2019 in a tertiary care hospital were retrospectively evaluated. After the etiologic distribution was determined, non-CAH PAI patients were evaluated in detail. Results: Seventy-three PAI patients were identified. The most common etiology was CAH (69.9%, n=51). Non-CAH etiologies accounted for 30.1% (n=22) and included adrenoleukodystrophy (ALD; n=8), familial glucocorticoid deficiency (n=3), Triple A syndrome (n=5), autoimmune adrenalitis (n=1), adrenal hypoplasia congenital (n=1), IMAGe syndrome (n=1), and other unknown etiologies (n=3). The median age at the time of AI diagnosis for non-CAH etiologies was 3.52 (0.03-15.17) years. The most frequent symptoms/clinical findings at onset were hyperpigmentation of skin (81.8%), symptoms of hypoglycemia (40.9%), and weakness/fatigue (31.8%). Hypoglycemia (50.0%), hyponatremia (36.4%) and hyperkalemia (22.7%) were prominent biochemical findings. Diagnosis of specific etiologies were proven genetically in 13 of 22 patients. A novel p.Q301* hemizygous frameshift mutation of the DAX1 gene was identified in one patient. Conclusion: Etiology was determined in 86.3% of children with non-CAH PAI through specific clinical and laboratory findings with/ without molecular analysis of candidate genes. ALD was the most common etiology. Currently, advanced molecular analysis can be utilized to establish a specific genetic diagnosis for PAI in patients who have no specific diagnostic features.

Difficulties Experienced by Turkish Parents and Their Coping Strategies: Children With Mucopolysaccharidosis.

PURPOSE: The purpose of this study is to determine the parents' lived experiences whose children have Mucopolysaccharidosis (MPS) by using Husserl's phenomenology. DESIGN AND METHODS: A phenomenology method was used as a qualitative research design in the study. The study included parents of 10 children who received weekly enzyme replacement therapy at a university hospital's paediatric endocrinology clinic. The data were collected using an in-depth interview method including an introductory information form and a semi-structured interview form. The interviews were recorded on a voice recorder and converted into written documents after the interview. RESULTS: The average age of the children was 8.8 ± 1.8; the average age of the mothers was 32.6 ± 3.6; and the average age of the fathers was 36.0 ± 3.5. The data analysis identified the following three main themes: (1) difficulties, (2) concerns, and (3) coping. CONCLUSIONS: This study determined that parents of children with an MPS diagnosis had many difficulties related to multi-systemic problems (orthopaedic problems, vision and hearing problems, speech disorders, cardiac problems) caused by the disease. PRACTICE IMPLICATIONS: Parents should receive support from healthcare professionals to develop coping strategies that are appropriate for the physical and psychological difficulties experienced and to comply with the disease.

Neonatal Screening for Congenital Adrenal Hyperplasia in Turkey: Outcomes of Extended Pilot Study in 241,083 Infants

Objective: Turkish Directorate of Public Health introduced the first pilot screening program for congenital adrenal hyperplasia (CAH) in four Turkish cities in 2017, and in 2018 extended the program, with a slight change in screening strategy, to fourteen cities. To evaluate the performance of the extended study and update previously reported outcomes. Methods: Retrospective, descriptive study. Neonates of ≥32 gestational weeks and ≥1500 gr birth weight from fourteen cities, born between May-December 2018, were included. Screening protocol included one sample, two-tier testing as applied in the previous pilot study. In the first step, 17α-hydroxyprogesterone (17-OHP) was measured by fluoroimmunoassay in dried blood spots (DBS) obtained at 3-5 days of life. Cases with positive initial screening underwent second tier testing by steroid profiling in DBS using liquid chromatographyt-andem mass spectrometry to measure 17-OHP, 21-deoxycortisol (21-S), cortisol (F), 11-deoxycortisol and androstenedione. The babies with a steroid ratio (21-S+17-OHP)/F of ≥0.7 (increased from ≥0.5 in the earlier pilot study) were referred to pediatric endocrinology clinics for diagnostic assessment. Results: In the evaluated period, 241,083 newborns were screened. 12,321 (5.11%) required second-tier testing and 880 (0.36%) were referred for clinical assessment, twenty of whom were diagnosed with CAH (10 females, 10 males). Sixteen were diagnosed as classical 21-hydroxylase deficiency (21-OHD) CAH (12 with salt-wasting and four with simple virilising CAH), and four cases were identified with 11ß-OHD CAH. No case of salt-wasting CAH was missed by neonatal screening (sensitivity was 100%). The incidence of classical 21-OHD and 11ß-OHD in the screened population was 1:15,067 and 1:60,270, respectively. Conclusion: Turkish neonatal CAH screening effectively led to earlier diagnosis of 21-OHD and 11ß-OHD, using steroid profiling as a second-tier test. This will result in improved care of these patients in the future.

The relationship between serum FGF-23 concentration and insulin resistance, prediabetes and dyslipidemia in obese children and adolescents.

Background Obesity is known to cause metabolic disturbances including insulin resistance, dyslipidemia and alters bone mineralization. The effects of obesity on fibroblast growth factor 23 (FGF-23), which is important in bone mineralization, have not yet been clarified. Our aim was to investigate the association between FGF-23 concentration and obesity-associated dysmetabolism. Methods Subjects comprised 46 obese children and adolescents. The same number of age-matched, healthy controls were recruited. Markers of bone mineralization and glucose metabolism were measured. Thyroid function and insulin resistance were investigated in both groups. In obese subjects; an oral glucose tolerance test (OGTT) was performed and hemoglobin A1c and lipid fractions were measured. Bone mineral density and hepatic steatosis were investigated. Results Serum FGF-23, α-klotho and 1,25(OH)2D3 concentrations were significantly lower while fasting insulin, fasting glucose, C-peptide and alkaline phosphatase (ALP) concentrations and homeostasis model assessment of insulin resistance (HOMA-IR) were significantly higher in the obese group compared to controls. A significant negative correlation was observed between free tri-iodothyronine (fT3) and both FGF-23 and α-klotho in the obese group. Significant negative correlation was found between FGF-23 and C-peptide and a positive correlation was found between FGF-23 and high density lipoprotein-cholesterol (HDL-c) in the obese subjects with impaired glucose tolerance (IGT). Significant negative correlations were found between FGF-23 and both fasting insulin levels and C-peptide levels in the obese subjects with hepatic steatosis. Conclusions In our study, insulin resistance-associated hyperinsulinism and/or lower 1,25(OH)2D3 levels, both present in obese children and adolescents, may lead to decreased serum FGF-23 concentrations in obese subjects.

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 non-syndromic 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.

The Effects of Two Different Burn Dressings on Serum Oxidative Stress Indicators in Children with Partial Burn.

In this study, we evaluated and compared the effect of treatment with a hydrofiber dressing with silver (HFAg) and a polylactic membrane (PLM) on systemic oxidative stress in systemic inflammatory reaction in thermal burn injuries in children. A prospective randomized and matched pairing study of 20 to 50% of TBSA was performed from children equal to both sexes affected by thermal injuries. The control group was included in normal children of both sexes. Serum malondialdehyde (MDA), total antioxidant capacity (TAC), total oxidant capacity (TOC), and glutathione (GSH) levels were analyzed and the results were analyzed statistically. In this study, it was found that PLM treatment increased TAC and GSH levels in burn patients significantly more than the other group. With the use of PLM, TOC decreased to normal level from day 3. In the HFAg group, TAC and GSH levels began to increase on the seventh day. On the first day of the burn, the TOC level started to increase. This increase continued on days 7 and 14. The TOC level began to fall on the 21st day. The increase in TAC was higher in the PLM group. In the PLM group, TOC fell faster. As a result, we think that different burn dressings can have different systemic effects. We can speculate that PLM has an antioxidant effect in the burn tissue due to high lactate content. Therefore, PLM may have decreased serum oxidative stress indicators more effectively than HFAg.