Publications by authors named "Damla Goksen"

66 Publications

The utility of reverse phenotyping: a case of lysinuric protein intolerance presented with childhood osteoporosis.

J Pediatr Endocrinol Metab 2021 Apr 7. Epub 2021 Apr 7.

Pediatric Genetics Subdivision, Department of Pediatrics, Faculty of Medicine, Ege University, Izmir, Turkey.

Objectives: Childhood osteoporosis is often a consequence of a chronic disease or its treatment. Lysinuric protein intolerance (LPI), a rare secondary cause of the osteoporosis, is an autosomal recessive disorder with clinical features ranging from minimal protein intolerance to severe multisystemic involvement. We report a case diagnosed to have LPI using a Next Generation Sequencing (NGS) panel and evaluate the utility of reverse phenotyping.

Case Presentation: A fifteen-year-old-boy with an initial diagnosis of osteogenesis imperfecta, was referred due to a number of atypical findings accompanying to osteoporosis such as splenomegaly and bicytopenia. A NGS panel (TruSight One Sequencing Panel) was performed and a novel homozygous mutation of c.257G>A (p.Gly86Glu) in the gene (NM_001126106.2), responsible for LPI, was detected. The diagnosis was confirmed via reverse phenotyping.

Conclusions: Reverse phenotyping using a multigene panel shortens the diagnostic process.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1515/jpem-2021-0018DOI Listing
April 2021

Glycemic Outcome Associated With Insulin Pump and Glucose Sensor Use in Children and Adolescents With Type 1 Diabetes. Data From the International Pediatric Registry SWEET.

Diabetes Care 2021 Mar 2. Epub 2021 Mar 2.

Starship Children's Health, Auckland, New Zealand.

Objective: Insulin delivery methods, glucose-monitoring modalities, and related outcomes were examined in a large, international, diverse cohort of children and adolescents with type 1 diabetes from the Better Control in Pediatric and Adolescent Diabetes: Working to Create Centers of Reference (SWEET) -Registry.

Research Design And Methods: Participants with type 1 diabetes of ≥1 year, aged ≤18 years, and who had documented pump or sensor usage during the period August 2017-July 2019 were stratified into four categories: injections-no sensor (referent); injections + sensor; pump-no sensor; and pump + sensor. HbA and proportion of patients with diabetic ketoacidosis (DKA) or severe hypoglycemia (SH) were analyzed; linear and logistic regression models adjusted for demographics, region, and gross domestic product per capita were applied.

Results: Data of 25,654 participants were analyzed. The proportions of participants (adjusted HbA data) by study group were as follows: injections-no sensor group, 37.44% (8.72; 95% CI 8.68-8.75); injections + sensor group, 14.98% (8.30; 95% CI 8.25-8.35); pump-no sensor group, 17.22% (8.07; 95% CI 8.03-8.12); and pump + sensor group, 30.35% (7.81; 95% CI 7.77-7.84). HbA was lower in all categories of participants who used a pump and/or sensor compared with the injections-no sensor treatment method ( < 0.001). The proportion of DKA episodes was lower in participants in the pump + sensor (1.98%; 95% CI 1.64-2.48; < 0.001) and the pump-no sensor (2.02%; 95% CI 1.64-2.48; < 0.05) groups when compared with those in the injections-no sensor group (2.91%; 95% CI 2.59-3.31). The proportion of participants experiencing SH was lower in pump-no sensor group (1.10%; 95% CI 0.85-1.43; < 0.001) but higher in the injections + sensor group (4.25%; 95% CI 3.65-4.95; < 0.001) compared with the injections-no sensor group (2.35%; 95% CI 2.04-2.71).

Conclusions: Lower HbA and fewer DKA episodes were observed in participants using either a pump or continuous glucose monitoring (CGM) or both. Pump use was associated with a lower rate of SH. Across SWEET centers, use of pumps and CGM is increasing. The concomitant use of pump and CGM was associated with an additive benefit.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.2337/dc20-1674DOI Listing
March 2021

Metabolic syndrome and risk factors after hematopoietic stem cell transplantation in children and adolescents.

J Pediatr Endocrinol Metab 2021 Apr 25;34(4):485-493. Epub 2021 Feb 25.

Department of Pediatric Hematology & Oncology and Bone Marrow Transplantation, Medical School of Ege University, Izmir, Turkey.

Objectives: The early and late complications after hematopoietic stem cell transplantation (HSCT) determine the patients' prognosis and life quality. We aim to determine the metabolic syndrome development frequency after HSCT in children to find out the risk factors and compare them with healthy adolescents.

Methods: Thirty-six children who underwent HSCT at least two years ago were analyzed prospectively and cross-sectionally. Our study included 18 healthy children between the ages of 11 and 17 as a control group. All of the cases were assessed in terms of metabolic syndrome (MS) through the use of Modified WHO Criteria.

Results: The patients' median age was 10.6 (5.1-17) years, the median time of follow-up after HCST was 4.1 (2-13.5) years and 70% were male. Two cases were diagnosed with MS (5.6%). When considered in terms of the sub-components of MS, 2 cases (5.6%) were found to have obesity, 17 cases (47%) abnormal glucose tolerance, 11 cases (30.7%) dyslipidemia, and 3 cases (8.6%) hypertension. The MS rate was not different when compared with the 11-17 year-old healthy control group (0 vs. 11%, p=0.48). Myeloablative conditioning regimen (65 vs. 20%) and the increased age at which HSCT was performed were considered to be risk factors in terms of insulin resistance (p=0.025 and 0.002).

Conclusions: Age and conditioning regimens were found to be the risk factors for insulin resistance development. The long-term follow-up of the cases who had undergone HSCT in childhood in terms of MS and its sub-components is important in order to increase life quality.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1515/jpem-2020-0584DOI Listing
April 2021

Glycated hemoglobin variability and microvascular complications in patients with type 1 diabetes mellitus.

J Pediatr Endocrinol Metab 2020 Dec 19;33(12):1533-1537. Epub 2020 Nov 19.

Department of Pediatrics, Faculty of Medicine, Division of Pediatric Endocrinology, School of Medicine, Ege University, İzmir, Turkey.

Objectives: Glycated hemoglobin (HbA1c) has proven to be indicative in the development of microvascular complications. In this study, the contribution of HbA1c variability to microvascular complications was evaluated.

Methods: Twenty-one cases with type 1 diabetes mellitus (T1DM) who developed microvascular complications and 39 cases without complications, that were similar in terms of gender, age of diagnosis, insulin treatment, insulin doses (U/kg), and mean HbA1c levels were included.

Results: Mean age of T1DM diagnosis was 5.87 ± 3.93 years in the complication group and 4.63 ± 3.33 years in the control group. Nephropathy was detected in 17 cases, neuropathy in 8 cases, and retinopathy in 1 case. Nephropathy occurred at a mean age of 11.52 ± 4.12 years and neuropathy at 14.13 ± 5.68 years. The mean HbA1c during follow-up was similar in the group with complications and the control group (8.60 ± 0.63 vs. 8.84 ± 1.32). Adjusted HbA1c-standard deviation (SD) and HbA1c-variation coefficient (CV) values were 1.30 ± 0.65 and 14.36 ± 6.23 in the group with complications (p=0.014), and 0.91 ± 0.37 and 10.59 ± 4.01 in the control group (p=0.013). In the Receiver Operating Characteristic (ROC)-analysis for microvascular complications, the limit value HbA1c-CV was 11.99 (sensitivity: 61.9%, specificity: 71.9%). This value for HbA1c-SD was 0.9699 (sensitivity: 71.43%, specificity: 66.67%).

Conclusions: This study has shown that long-term fluctuations in HbA1c are associated with the development of microvascular complications in type 1 diabetes.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1515/jpem-2020-0337DOI Listing
December 2020

Clinical Characteristics and Growth Hormone Treatment in Patients with Prader-Willi Syndrome.

J Clin Res Pediatr Endocrinol 2021 Feb 10. Epub 2021 Feb 10.

Istanbul University- Cerrahpasa, Cerrahpasa Medical Faculty, Department of Pediatric Endocrinology, Istanbul, Turkey.

Objective: To investigate clinical characteristics and response to growth hormone (GH) treatment in patients with Prader-Willi syndrome (PWS) in Turkey.

Methods: The data of 52 PWS patients from ten centers was retrospectively analyzed. A nation-wide, web-based data system was used for data collection. Demographic, clinical, genetic, and laboratory data and follow-up information of the patients were evaluated.

Results: The median age of patients at presentation was 1.5 years, and 50% were females. Genetic analysis showed microdeletion in 69.2%, uniparental disomy in 11.5%, imprinting defect in 1.9% and methylation abnormality in 17.3%. Hypotonia (55.7%), feeding difficulties (36.5%) and obesity (30.7%) were the most common complaints. Cryptorchidism and micropenis were present in 69.2% and 15.3% of males, respectively. At presentation, 25% had short stature, 44.2% were obese, 9.6% were overweight and 17.3% were underweight. Median age of obese patients was significantly higher than underweight patients. Central hypothyroidism and adrenal insufficiency were present in 30.7% and 4.7%, respectively. Hypogonadism was present in 75% at normal age of puberty. Growth hormone treatment was started in 40% at a mean age of 4.7±2.7 years. After two years of GH treatment, a significant increase in height SDS was observed. However, BMI SDS remained unchanged.

Conclusion: The most frequent complaints were hypotonia and feeding difficulty at first presentation. Obesity was the initial finding in 44.2%. Growth hormone treatment was started in less than half of the patients. While GH treatment significantly increased height SDS, BMI SDS remained unchanged, possibly due to the relatively older age at GH start.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.4274/jcrpe.galenos.2021.2020.0228DOI Listing
February 2021

Treatment and long-term follow-up of patients diagnosed with type 1 diabetes mellitus before age 5.

J Pediatr Endocrinol Metab 2021 Feb 18;34(2):201-207. Epub 2020 Dec 18.

Department of Pediatrics, Division of Pediatric Endocrinology, Faculty of Medicine, Ege University, Izmir, Turkey.

Objectives: This study aimed to determine the effects of continuous subcutaneous insulin infusion (CSII) treatment on anthropometric measurements, mean HbA1c, and insulin dosage in patients diagnosed under 5 years of age and compare with multiple-dose injection therapy (MDI).

Methods: Children with type 1 diabetes mellitus, diagnosed <5 years since 2000 and their 19-year follow-up were evaluated retrospectively. Weight, height, body mass index (BMI), blood pressure, and HbA1c values were recorded for each visit.

Results: Hundred and five patients (58.1% female, 41.9% male) were included in the study. Sixty-three (60 %) patients were treated by CSII and 42 (40%) by MDI. Mean age at diagnosis was 2.68 ± 1.42 and 3.29 ± 1.30 years respectively. Mean follow-up was 7.42 ± 4.76 and 6.01 ± 4.41 years respectively. For each group, weight standard deviation score (SDS) increased significantly in the first year after the diagnosis (p<0.001), and with the onset of puberty weight SDS decreased significantly (p<0.001). The trend of weight and BMI SDS changes over the years showed similar characteristics in both groups. During follow-up height SDS was similar in both groups except in Tanner stage 5. When puberty was completed, mean height SDS was 0.51 ± 1.03 in CSII and -0.31 ± 0.75 in the MDI group (p: 0.029). Mean HbA1c was significantly lower in the CSII group (7.62 ± 0.82 and 8.17 ± 1.22 respectively). Systolic and diastolic blood pressure change trends during the follow-up were also similar in both groups.

Conclusions: CSII treatment had positive effects on metabolic control and height SDS in patients with early-onset diabetes without increasing BMI.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1515/jpem-2020-0205DOI Listing
February 2021

A large cohort of disorders of sex development and their genetic characteristics: 6 novel mutations in known genes.

Eur J Med Genet 2021 Mar 29;64(3):104154. Epub 2021 Jan 29.

Department of Pediatric Endocrinology and Diabetes, Faculty of Medicine, Ege University, Izmir, Turkey.

Introduction: Disorders of sex development (DSD) constitutes a group of congenital conditions that affect urogenital differentiation and are associated with chromosomal, gonadal and phenotypic sex abnormalities.

Objective: To evaluate the clinical and genetic features of childhood DSD cases.

Materials And Methods: DSD patients followed up between the years of 2002-2018 were evaluated in terms of their complaints, demographic, clinical features and genetic diagnoses.

Results: Out of 289 patients, 143(49.5%) were classified as 46XY DSD, 62(21.5%) as 46XX DSD and 84(29%) as sex chromosomal DSD. Genetic diagnosis was achieved in 150 patients (51.9%). The distribution of the molecular diagnosis of the 46XY DSD patients were; 12 (26.6%) SRD5A2, 10 (22.2%) AR, 7 (15.5%) HSD17B3, 3 (6.6%) WT-1, 2 (4.4%) AMHR2, 2 (4.4%) AMH, 2 (4.4%) LHCGR, 2 (4.4%) HSD3B2, 1 (2.2%) NR5A1, 1 (2.2%) CYP17A1 and 1 (2.2%) SRY mutation. Fifty (80.6%) of the 46XX DSD patients received a diagnosis with clinical and laboratory findings. Twenty-four (38.7%) of them were 21-hydroxylase deficiency, 9(14.5%) Rokitansky-Küster-Hauser Syndrome, 4 (6.5%) 11-β hydroxylase deficiency, 3 (4.8%) gonadal dysgenesis and 2 (3.2%) aromatase deficiency. In 46XX group pathogenic mutations were detected in 21(33.8%) of the patients. Eighty-four (29%) patients were diagnosed as sex chromosomal disorder. Of these 66 (78.5%) were Turner Syndrome, 6 (7.2%) Klinefelter Syndrome and 10 (11.9%) mix gonadal dysgenesis. Gender re-assignment was decided in 11 patients. Malignant and pre-invasive lesions was diagnosed in 8 (2.7%) patients.

Conclusion: Many of DSD's are clinically similar and etiology of numerous of them still cannot be established. A multi-disciplinary approach and new rapid genetic diagnostic methods are needed in the process from diagnosis to gender assignment and follow-up.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ejmg.2021.104154DOI Listing
March 2021

Lower HbA1c targets are associated with better metabolic control.

Eur J Pediatr 2021 May 7;180(5):1513-1520. Epub 2021 Jan 7.

Department of Pediatrics, University Hospitals Leuven, Leuven, Belgium.

Previous studies have suggested that clear HbA1c target setting by the diabetes team is associated with HbA1c outcomes in adolescents. The aim of this study was to evaluate whether this finding is consistent in a larger cohort of children from centers participating in the SWEET international diabetes registry. A questionnaire was sent out to 76 SWEET centers, of which responses from 53 pediatric centers were included (70%). Descriptive outcomes were presented as median with lower and upper quartile. The association between the centers' target HbA1c and mean outcome HbA1c was calculated using linear regression adjusted for age, diabetes duration, sex, and gross domestic product. Median age of the children in the studied centers (n = 35,483) was 13.3 [12.6-14.6] years (49% female). Of the 53 centers, 13.2% reported an HbA1c target between 6.0 and 6.5%, 32.1% had a target between ≥ 6.0 and 7.0%, 18.9% between ≥ 7.0 and 7.5%, and 3.8% between ≥ 7.5 and 8.5%. No specific target value was reported by 32.1% of all centers. Median HbA1c across all centers was 7.9 [7.6-8.3] %. Adjusted regression analysis showed a positive association between HbA1c outcome and target HbA1c (p = 0.005).Conclusions: This international study demonstrated that a lower target for HbA1c was associated with better metabolic control. It is unclear whether low target values result in better metabolic control, or lower HbA1c values actually result in more ambitious target values. This target setting could contribute to the differences in HbA1c values between centers and could be an approach for improving metabolic outcomes. What is Known: • Target setting of HbA1c is important in children and adolescents with type 1 diabetes. • The optimal therapeutic approach of children with type 1 diabetes requires a trained multidisciplinary team. What is New: • Lower HbA1c targets are associated with better metabolic control. • No associations between the composition of the diabetes teams and metabolic control could be demonstrated.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00431-020-03891-2DOI Listing
May 2021

Initial Basal and Bolus Rates and Basal Rate Variability During Pump Treatment in Children and Adolescents.

J Clin Res Pediatr Endocrinol 2020 Dec 30. Epub 2020 Dec 30.

Division of Pediatric Endocrinology, Department of Pediatrics, School of Medicine, Ege University, İzmir, Turkey.

Objective: Pump-treated children with type 1 diabetes have widely differing basal insulin infusion profiles for specific periods of the day. The pattern of basal insulin requirements depends on the timing and magnitude of cortisol and growth hormone secretion within each age group. In adolescents and young adults, a decreased insulin sensitivity is seen, particularly in the early morning (dawn phenomenon) and of lesser extent, in the late afternoon (dusk phenomenon). Different approaches exist for the inititation of basal rates however, there is a lack of evidence-based recommendation, especially in young children. Usually the basal rates are set equally throughout day and night or the day is divided into tertiles. The aim of our study was to analyze the change of the initial equally distributed basal insulin rates over time of standart insulin pump therapy.

Methods: A total of 154 children with T1D, aged between 0 and <21 yrs, from a single center were documented. Children with T1D were divided into five age groups, group 1; <5 yr (n = 36); group 2; 5 to 8 yrs (n =20); group 3; 8 to 15 yrs (n=74); group 4; 15 to18 yrs,(n = 19) group 5; >18 yrs, (n = 5). Distribution of hourly basal rates at the initiation of the pump and at the end of first year were evaluated.

Result: Median age and diabetes duration was 14.46 (min:1.91/max:26.15) and 7.89 (±3.8) yrs (min:1.16/max:17.15) respectively. Forty-four percent were male, 56% were female. Mean total insulin dose/kg at the initiation and 1 st year of pump therapy was 0.86±0.23 U/kg and 0.78±0.19 U/kg in all participants respectively and differs in each age group (p<0.001; p<0.001). Mean daily basal rate/ kg showed substantial differences between the five groups (p<0.001). Circadian distribution of basal insulin differed markedly among the five age groups.

Conclusions: At the initiation of the insulin pump therapy, circadian profiles by age group should be taken into account when initiating CSII therapy in pediatric patients to optimize basal rate faster and easier.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.4274/jcrpe.galenos.2020.2020.0171DOI Listing
December 2020

The Value of Telemedicine for the Follow-up of Patients with New Onset Type 1 Diabetes Mellitus During COVID-19 Pandemic in Turkey: A Report of Eight Cases.

J Clin Res Pediatr Endocrinol 2020 Oct 21. Epub 2020 Oct 21.

Division of Pediatric Endocrinology, Department of Pediatrics, School of Medicine, Ege University, İzmir, Turkey.

Background: The current COVID-19 pandemic has forced health care teams to look for alternative approaches to manage a great number of children with diabetes not only in rural but also in urban locations. Our aim in this COVID-19 pandemic was to provide information about the follow-up of new onset type 1 diabetes (T1D) patients and to discuss the integration of telemedicine into routine clinical care in the long term.

Methods: The changes in Coefficient of variation (CV), standard deviation (SD); percentage of time in range (TIR), time below range (TBR) and time above range (TAR) were evaluated in 8 patients with new-onset T1D diagnosed in Pediatric Diabetes division of Ege University, during COVID-19 pandemic over a period of two-months follow-up using telemedicine system.

Results: Median follow-up time was 51 (24-66) days. Two of the patients were using low glucose suspend system and 6 were on multiple dose daily injection therapy (MDI). Target TIR values were achieved in 7 patients in the last televisit and according to last consensus suggestions' TBR <70 mg/dl (3.9 mmol/l) (level 1 hypoglycemia) of <4% and a TBR <54 mg/dl (3.0 mmol/l) (level 2 hypoglycemia) of <1% were achieved in all patients. Seven patients achieved a CV of < 36 % in their last televisit.

Conclusions: Telemedicine as an alternative follow-up tool during unusual circumstances such pandemics, even in countries where it is not routinely used, could be beneficial to achieve optimum glycemic control in patients with new-onset T1D.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.4274/jcrpe.galenos.2020.2020.0160DOI Listing
October 2020

A Remarkable Coexistence of Systemic Capillary Leak Syndrome and Diabetes in an 11-Year-Old Boy: A Case Report and Review of the Literature.

Case Reports Immunol 2020 1;2020:8891902. Epub 2020 Sep 1.

Division of Pediatric Endocrinology, Department of Pediatrics, Ege University Faculty of Medicine, İzmir, Turkey.

Systemic capillary leak syndrome (ISCLS) is a rare disease characterized by unexplained reversible capillary hyperpermeability followed by hypoperfusion, hemoconcentration, and either hypoalbuminemia or total hypoproteinemia. An 11-year-old boy was admitted with vomiting, generalized edema, and hyperglycemia, which was preceded by 5 days of coryzal symptoms, lethargy, and oral aft, without fever. On physical examination, he had tachycardia and hypotension, with severe generalized systemic nonitchy edema, and the laboratory tests supported the conclusion that he had severe hemoconcentration with hemoglobin: 184 g/L, hematocrit: 51.3 %, urea: 20 mmol/L, blood glucose: 11.1 mmol/L, and albumin: 19 gr/L, with normal urine analysis. On the fourth day, the patient was diagnosed with ISCLS, by ruling out other causes of shock and hypoalbuminemia. Intravenous immunoglobulin (IVIG) treatment regimen was administered on two consecutive days (day five and day six). His edema decreased on the fifth day, and the patient was deemed clinically well. There was no compartment syndrome, rhabdomyolysis, or pulmonary edema in the recovery period. However, respiratory virus panel PCR was positive for respiratory syncytial virus (RSV) and enterovirus, which were thought to be the triggering cause of ISCLS. For the differential diagnosis of diabetes, his fasting serum glucose was 13.4 mmol/L, simultaneous C-peptide was 0.44 nmol/L, and HbA1c was 64 mmol/mol, and urine ketone was positive. However, antiglutamic acid decarboxylase, anti-insulin antibody, and islet cell antibody were negative. At the last outpatient visit, 22 months after the diagnosis, his insulin dose was still 0.4 IU/kg/day and HbA1c was 40 mmol/mol, and without prophylaxis, there was no ISCLS attack. . Early recognition of ISCLS is important for therapeutic awareness, since it is very rare in childhood and occurs usually without any prior provoking factors in healthy children. With the increase in awareness of the disease, knowledge and experiences about pediatric patients may also increase. We think that our case will contribute to the literature since there have been no pediatric diabetic patients with ISCLS reported.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1155/2020/8891902DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7482009PMC
September 2020

Quality of Life and Psychological Well-being in Children and Adolescents with Disorders of Sex Development

J Clin Res Pediatr Endocrinol 2021 02 17;13(1):23-33. Epub 2020 Sep 17.

Ege University Faculty of Medicine, Department of Pediatric Endocrinology, İzmir, Turkey

Objective: The aim of this study was to assess the quality of life (QoL) and psychological well-being in child and adolescent with disorders of sex development (DSD).

Methods: Sixty-two cases, aged 2-18 years, who were followed by a multidisciplinary DSD team were included. All participants and their parents were requested the complete the Pediatric Quality Of Life Inventory (PedsQL) and the Strengths and Difficulties Questionnaire. The psychiatric diagnoses of the patients were evaluated according to Schedule for Affective Disorders and Schizophrenia for School-Age Children/Present and Lifetime Turkish Version.

Results: There was no significant difference between the 46,XX DSD and 46,XY DSD groups for both child and parent in Total PedsQL score. In the subscale scores, the PedsQL Physical Functionality Score reported by children was significantly lower for the 46,XX DSD group than for the 46,XY DSD group (p=0.01). There was a psychiatric diagnosis in 25.8% of cases. The PedsQL School Functionality Score reported by children in the group with psychiatric diagnosis was significantly lower than the group without psychiatric diagnosis (p=0.018). In the group with psychiatric diagnosis, the PedsQL Total Score and the subscale scores (Emotional Functionality Score, Social Functionality Score, School Functionality) reported by parents were significantly lower than in parents of the group without psychiatric diagnosis.

Conclusion: This study emphasized that psychiatric disorders in DSD patients negatively affect the QoL. Psychiatric support and counseling from a multidisciplinary team are very important for families affected by DSD.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.4274/jcrpe.galenos.2020.2020.0141DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7947730PMC
February 2021

A New Cause of Obesity Syndrome Associated with a Mutation in the Carboxypeptidase Gene Detected in Three Siblings with Obesity, Intellectual Disability and Hypogonadotropic Hypogonadism

J Clin Res Pediatr Endocrinol 2021 02 17;13(1):52-60. Epub 2020 Sep 17.

Ege University Faculty of Medicine, Department of Medical Genetics, İzmir, Turkey

Objective: Carboxypeptidase E (CPE) plays a critical role in the biosynthesis of peptide hormones and neuropeptides in the endocrine system and central nervous system. knockout mice models exhibit disorders such as diabetes, hyperproinsulinaemia, low bone mineral density and neurodevelopmental disorders. Only one patient is described with morbid obesity, intellectual disability, abnormal glucose homeostasis and hypogonadotropic hypogonadism, which was associated with a homozygous frameshift deletion in .

Methods: Herein are described three siblings with obesity, intellectual disability and hypogonadotropic hypogonadism. Whole exome sequencing (WES) was performed in the index case. Candidate variants were prioritised and segregation of the variant, consistent with the phenotype of the index case, was assessed by Sanger sequencing in affected siblings and parents.

Results: WES analysis revealed a homozygous nonsense c.405C>A (p.Y135*) mutation in . Validation and segregation analysis confirmed the homozygous mutation in the index case and his affected siblings. The parents were phenotypically normal heterozygous mutation carriers.

Conclusion: This study provides additional evidence of the association between a homozygous nonsense mutation in and a clinical phenotype consisting of obesity, intellectual disability and hypogonadotropic hypogonadism, which may be considered as a new monogenic obesity syndrome.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.4274/jcrpe.galenos.2020.2020.0101DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7947731PMC
February 2021

Psychiatric view for disorders of sex development: a 12-year experience of a multidisciplinary team in a university hospital.

J Pediatr Endocrinol Metab 2020 May;33(5):605-611

Ege University Faculty of Medicine, Department of Pediatric Endocrinology, İzmir, Turkey.

Background Psychiatric consultation is important in the follow-up of disorders of sex development (DSD) patients. In this study, we aimed to present the 12-year psychiatric follow-up data of the patients who were referred by Ege University Medical Faculty DSD Multidisciplinary Team and followed up in Child and Adolescent Psychiatry. Methods Psychiatric data of 118 patients, who were followed by the DSD multidisciplinary team between 2007 and 2019, were reviewed retrospectively. The psychiatric diagnoses of the patients were evaluated according to semi-structured interview form Schedule for Affective Disorders and Schizophrenia for School-Age Children/Present and Lifetime Turkish Version. Results The mean age of the 118 cases was 13.21 years (±7.18). Endocrine diagnoses of the cases were 46 XX DSD in 35 (29.6%), 46 XY DSD in 81 (68.7%), and chromosome disorders in 2 (1.7%). There was at least psychiatric diagnosis in 36 (30.5%) cases. The most common psychiatric diagnosis was attention deficit and hyperactivity disorder (ADHD) (n = 18, 15.3%). ADHD was most common in congenital adrenal hyperplasia (n = 4, 22.4%) and androgen synthesis defects (ASD) (n = 4, 22.4%); depression was most common in complete gonadal dysgenesis and ASD (n = 3, 23.1%); and mental retardation was most common in ASD (n = 3, 37.5%). Conclusions In order to provide a healthy perspective for cases with DSD, it is important to make a psychiatric evaluation and to share observations and clinical findings in regular team meetings.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1515/jpem-2019-0513DOI Listing
May 2020

Melanocortin 4 receptor (MC4R) gene variants in children and adolescents having familial early-onset obesity: genetic and clinical characteristics.

Eur J Pediatr 2020 Sep 18;179(9):1445-1452. Epub 2020 Mar 18.

Department of Medical Genetics, Ege University School of Medicine, İzmir, Turkey.

Melanocortin 4 receptor gene plays an important role in food intake, energy balance, and weight control. The autosomal dominantly inherited MC4R variants cause obesity by causing hyperphagia and decreased sense of satiety. Homozygous variants are rarely reported, and they cause earlier/severe obesity. Our objective is to determine the MC4R gene variant frequency in children and adolescents with familial early-onset obesity. One hundred thirty-nine children and adolescents (57 girls/82 boys) whose weight increase started before the age of 5 years and who had early-onset obesity in at least one of their first-degree relatives were included in the study. Obesity is defined as body mass index (BMI) of ≥ 95th percentile, and as extreme obesity is defined if the BMI ≥ 120% of the 95th percentile or ≥ 35 kg/m. Children having genetic syndromes associated with obesity and mental retardation or taking drugs that promote changes in eating behavior or weight were excluded from the study. Coding region of the MC4R gene was sequenced by using the Illumina MiSeq Next Generation Sequencing System. The mean age of the patients was 7.3 ± 3.7 years, and the mean BMI SDS was 3.7 ± 0.7. While 118 patients (85%) were prepubertal, 21 patients (15%) were pubertal. Seven different variants were identified in 12 patients by giving a variant detection rate of 8.6%, of these five were previously identified missense variants p.N274S, p.S136F, p.V166I, p.R165W, and p.I291SfsX10. One homozygous variant p.I291SfsX10 (c.870delG) was detected in a severely obese 2-year-old boy, and other variants were heterozygous. Two novel variants were found: p.M200del and p.S188L. By using the in silico analysis software, these novel variants were predicted to be disease causing.Conclusion: MC4R gene variants are quite common in childhood obesity in Turkish population. Screening the variants in MC4R gene is necessary in patients with severe childhood-onset obesity. In such patients, comorbidities of obesity can be seen from early years. What is known • The frequency of MC4R mutations in obese patients was approximately 0-6.3%. What is new • In obese Turkish pediatric population, unlike other European countries, MC4R gene variants are quite common as we found a variant rate of 8.6% • We believe it is necessary to screen the variants in MC4R gene in patients with severe childhood-onset obesity and who had early-onset obesity in at least one of their first-degree relatives in Turkish population.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00431-020-03630-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7223532PMC
September 2020

Exploring emotional dysregulation characteristics and comorbid psychiatric disorders in type 1 diabetic children with disordered eating behavior risk.

J Psychosom Res 2020 Feb 11;131:109960. Epub 2020 Feb 11.

Ege University School of Medicine, Department of Child Endocrinology, Izmir, Turkey.

Objective: To investigate emotional dysregulation and psychiatric comorbidities associated with DEB-risk in children with type 1 diabetes mellitus (T1DM).

Methods: A total of 75 children with T1DM aged between 8 and 19 were evaluated by K-SADS-PL to assess psychiatric diagnosis. DEB-risk was evaluated via Diabetes Eating Problem Survey-Revised (DEPS-R). Besides, all participants completed the Childhood Depression Inventory (CDI), Difficulties in Emotion Regulation Scale (DERS), and The State-Trait Anxiety Inventory (STAI).

Results: DEPS-R-positive (≥20) was detected in 28% of the participants. The only diagnostic difference was a significantly higher frequency of ED in DEPS-R-positive than DEPS-R-negative (OR = 8.5, CI = 1.94-37.1, p = .004). DEPS-R-positive cases had significantly higher scores of the CDI, STAI, DERS, and the subscales of Goals, Impulse, and Strategies of DERS (CDI U = 266.500, p = .001; STAI U = 288.500,p = .001; DERS U = 229.000, p = .001, Goals U = 283.500, p = .008, Impulse U = 274.000, p = .005, Strategies U = 281.500, p = .007). In stepwise linear regression analysis, STAI-state and DERS scores significantly determined DEB-risk (STAI: β = 0.363, t(60) = 2.33, p = .02, DERS: β = 0.240, t(60) = 4.14, p < .001).

Conclusion: This cross-sectional study showed that DEPS-R-positive cases have an 8.5-fold increased risk for ED. DEPS-R-positive ones have difficulties in regulating their emotions and they are incapable of accessing emotion regulation strategies, engaging in goal-directed behavior while under difficult emotions, and impulse control. It can be beneficial for child psychiatrists to screen first for ED in DEPS-R-positive cases who are referred by child endocrinologist. They should also take into consideration anxiety levels and problems in emotion dysregulation in the DEPS-R-positive cases.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jpsychores.2020.109960DOI Listing
February 2020

The Effects of Prehospital Care on Outcome in Pediatric Diabetic Ketoacidosis

J Clin Res Pediatr Endocrinol 2020 06 14;12(2):189-196. Epub 2019 Nov 14.

Ege University Faculty of Medicine, Department of Pediatrics, Division of Pediatric Emergency, İzmir, Turkey

Objective: Despite the guidelines, significant variations can be encountered in initial therapy for pediatric diabetic ketoacidosis (DKA) in the prehospital setting. These variations occur mostly in fluid administration, insulin dosing, route of administration, and other aspects of the initial resuscitation and stabilization. The aim was to identify the effect of transport care on outcomes in children with DKA admitted to the emergency department (ED).

Methods: Patients admitted to a tertiary-care pediatric ED between 2015-2019 with a diagnosis of DKA were retrospectively identified. Details of pre-pediatric ED care, including transport modality, patient demographics, clinical features, laboratory evaluation, fluid therapy, insulin dosing, and short-term outcome were recorded.

Results: The study cohort included 147 episodes of DKA in 136 patients aged 9 months-21 years. Emergency Medical Service (EMS) transported only 37.4% of cases. EMS utilization rate was significantly higher (p=0.003) in severe cases, most of whom were >10 years (p=0.04). During transport 85% received intravenous fluid bolus. Use of fluids other than normal saline was significantly higher when transport time was >30 minutes (p=0.001). Acute kidney injury and cerebral edema developed in 21.7% and 7.4% of episodes, respectively. These complications were more common in the EMS transport group. Pediatric intensive care admission rate was also higher in the EMS compared to the non-EMS group (p=0.01).

Conclusion: Parents did not call the ambulance for most cases although a higher complication rate occurred in EMS patients. EMS providers and referral facilities should improve their knowledge of pediatric DKA.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.4274/jcrpe.galenos.2019.2019.0121DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7291399PMC
June 2020

Nationwide Turkish Cohort Study of Hypophosphatemic Rickets

J Clin Res Pediatr Endocrinol 2020 06 13;12(2):150-159. Epub 2019 Sep 13.

Ankara University Faculty of Medicine, Department of Pediatric Endocrinology, Ankara, Turkey

Objective: Hypophosphatemic rickets (HR) is a rare renal phosphate-wasting disorder, which is usually X-linked and is commonly caused by PHEX mutations. The treatment and follow-up of HR is challenging due to imperfect treatment options.

Methods: Here we present nationwide initial and follow-up data on HR.

Results: From 24 centers, 166 patients were included in the study. Genetic analysis (n=75) showed mutation in 80% of patients. The mean follow-up period was 6.7±2.4 years. During the first 3-years of treatment (n=91), mild increase in phosphate, decrease in alkaline phosphatase and elevation in parathyroid hormone (PTH) levels were detected. The height standard deviation scores were -2.38, -2.77, -2.72, -2.47 at initial, 1, 2 and 3 year of treatment, respectively (p>0.05). On follow-up 36% of the patients showed complete or significant improvement in leg deformities and these patients had similar phosphate levels at presentation with better levels in 1 and 2 years of treatment; even the treatment doses of phosphate were similar. Furthermore, 27 patients developed nephrocalcinosis (NC), the patients showed no difference in biochemical differences at presentation and follow-up, but 3 year PTH was higher. However, higher treatment doses of phosphate and calcitriol were found in the NC group.

Conclusion: HR treatment and follow-up is challenging and our results showed higher treatment doses were associated with NC without any change in serum phosphate levels, suggesting that giving higher doses led to increased phosphaturia, probably through stimulation of fibroblast growth factor 23. However, higher calcitriol doses could improve bone deformities. Safer and more efficacious therapies are needed.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.4274/jcrpe.galenos.2019.2019.0098DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7291408PMC
June 2020

Correction to: The Gonadotropin-Releasing Hormone Analogue Therapy May Not Impact Final Height in Precocious Puberty of Girls With Onset of Puberty Aged 6 - 8 Years.

J Clin Med Res 2019 Jun 10;11(6):464. Epub 2019 May 10.

Department of Pediatric Endocrinology, School of Medicine, Ege University, Izmir, Turkey.

[This corrects the article DOI: 10.14740/jocmr3710.].
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.14740/jocmr3710-cDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6522235PMC
June 2019

Aromatase Deficiency in Two Siblings with 46,XX Karyotype Raised as Different Genders: A Novel Mutation (p.R115X) in the Gene

J Clin Res Pediatr Endocrinol 2020 03 10;12(1):109-112. Epub 2019 Apr 10.

Ege University Faculty of Medicine, Department of Pediatric Endocrinology, İzmir, Turkey

Aromatase deficiency rarely causes a 46,XX sexual differentiation disorder. The gene encodes the aromatase enzyme which catalyses the conversion of androgens to oestrogens. In cases with 46,XX karyotype, mutations in the gene can lead to disorders of sex development. Clinical findings in aromatase deficiency vary depending on the degree of deficiency. The effect of increased androgens, including acne, cliteromegaly and hirsutism, can be observed in mothers with placental aromatase deficiency. A decrease in maternal virilisation symptoms is observable in the postpartum period. It is rarely reported that there is no virilization in pregnancy. In this study, two 46,XX sibling having the p.R115X (c.343 C>T) novel pathogenic variant in the gene and raised as different genders, with no maternal virilisation during pregnancy, are presented. In conclusion, 46,XX virilised females should be examined in terms of aromatase deficiency once congenital adrenal hyperplasia has been excluded, even if there is no history of maternal virilisation during pregnancy.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.4274/jcrpe.galenos.2019.2018.0198DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7127884PMC
March 2020

A novel thyroid hormone receptor alpha gene mutation, clinic characteristics, and follow-up findings in a patient with thyroid hormone resistance.

Hormones (Athens) 2019 Jun 12;18(2):223-227. Epub 2019 Feb 12.

Ege University Faculty of Medicine Department of Pediatric Endocrinology and Diabetes, Ege University, 35100 Bornova, Izmir, Turkey.

Thyroid hormone receptor alpha (THRA) gene mutation is a thyroid hormone resistance syndrome characterized by near-normal thyroid function tests and tissue-specific hypothyroidism. In this case study, we report a novel de novo p.G291S heterozygous mutation in the THRA gene was detected at mutation analysis. A 4-year-old male patient was admitted due to short stature, motor-mental retardation, and constipation. At physical examination, coarse facial appearance, eyelid edema, pallor, and umbilical hernia were observed. Primary thyroid hormone resistance should be considered in patients with phenotypically hypothyroid features. Laboratory analysis found moderate elevation in free triiodothyronine (T3) levels, normochromic normocytic anemia, and elevated creatine kinase levels. In conclusion, THRA gene mutation should be considered in patients with clinical hypothyroid findings and increased/moderately elevated free T3, decreased/ normal free thyroxine, normal thyroid-stimulating hormone levels, and increased muscle enzymes.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s42000-019-00094-9DOI Listing
June 2019

Effect of Education on Impaired Hypoglycemia Awareness and Glycemic Variability in Children and Adolescents with Type 1 Diabetes Mellitus

J Clin Res Pediatr Endocrinol 2019 05 31;11(2):189-195. Epub 2019 Jan 31.

Ege University Faculty of Medicine, Department of Pediatric Endocrinology and Diabetes, İzmir, Turkey

Objective: The aim of this study was to determine the prevalence of impaired hypoglycemia awareness (IHA) in children and adolescents with type 1 diabetes mellitus using a professional continuous glucose monitoring (CGM) system and to show the effect of structured education on glycemic variability (GV) in children and adolescents with IHA.

Methods: Forty type 1 diabetic children and adolescents with a diabetes duration of at least five years were eligible for inclusion in this prospective, quantitative study. All subjects were asked about their history of being aware of the symptoms of hypoglycemia using a questionnaire. Professional CGM was conducted in all of the patients for six days. The frequency of IHA detected by comparison of CGM and logbook reports were analyzed. Patients with identified IHA underwent a structured training program. After three months, CGM was re-applied to patients with IHA.

Results: The study was completed by 37 diabetic children and adolescents. After the initial CGM, nine patients (24.3%) were found to have had episodes of IHA. Area under the curve (AUC) for hypoglycemia and number of low excursions were; 1.81±0.95 and 8.33±3.60 for the IHA group at the beginning of the study. AUC for hypoglycemia was 0.43±0.47 after three months of structured education the IHA patients (p=0.01). Coefficient of variation which shows primary GV decreased significantly although unstable at the end of education in IHA patients (p=0.03).

Conclusion: CGM is a valuable tool to diagnose IHA. IHA, GV and time in range can be improved by education-based intervention.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.4274/jcrpe.galenos.2019.2019.0009DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6571530PMC
May 2019

The Gonadotropin-Releasing Hormone Analogue Therapy May Not Impact Final Height in Precocious Puberty of Girls With Onset of Puberty Aged 6 - 8 Years.

J Clin Med Res 2019 Feb 5;11(2):133-136. Epub 2019 Jan 5.

Department of Pediatric Endocrinology, School of Medicine, Ege University, Izmir, Turkey.

Background: The effect on final height of gonadotropin-releasing hormone analogues (GnRHa) used in the treatment of precocious puberty is controversial. The aim of this study was to determine whether or not GnRHa therapy would make any contribution to final height in precocious puberty of girls with onset of pubertal characteristic development aged 6 - 8 years.

Methods: Age at start of puberty, target height standard deviation score (SDS) presentation, follow-up height SDS, body mass index (BMI) SDS, bone age and predicted adult height of 34 female subjects who had reached their final height and with pubertal findings beginning at the ages of 6 - 8 were evaluated. These subjects were divided into two groups: treatment and non-treatment groups. The treatment group was further divided into two subgroups, receiving monthly or three-monthly depot GnRHa.

Results: Age at onset of puberty was 7.2 ± 0.9 years. Twenty-five cases were started on GnRHa and nine were followed-up without treatment. Fourteen cases received monthly 3.75 mg depot triptorelin acetate and 11 received three-monthly 11.25 mg depot. Mean age at start of treatment in the treatment group was 9.1 ± 1.2 years and mean bone age was 9.7 ± 2.3 years. Age at presentation in the non-treatment group was 8.4 ± 1.4 years and bone age was 10.3 ± 2.1 years. Target and final height SDS were similar in all the groups (P > 0.05). No difference was determined between the treatment groups in terms of initial height SDS, bone age, length of treatment, final height SDS or BMI SDS (P > 0.05).

Conclusions: GnRHa therapy did not make a positive contribution to final height in precocious puberty of girls with onset of puberty aged 6 - 8 years.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.14740/jocmr3710DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6340673PMC
February 2019

Parental Perception of Terminology of Disorders of Sex Development in Western Turkey

J Clin Res Pediatr Endocrinol 2018 07 29;10(3):216-222. Epub 2018 Mar 29.

Ege University Faculty of Medicine, Department of Pediatric Surgery, Division of Pediatric Urology, İzmir, Turkey

Objective: Disorders of sex development (DSD) is a nomenclature intended to defeat the discomfort of families and patients and has found worldwide usage. The aim of this study was to address the perception and usage of terminology among the parents of DSD patients in a tertiary center in western Turkey.

Methods: The records of the DSD council (multidisciplinary team where each patient with DSD is discussed) between years 2008-2015 were reviewed retrospectively. Data including details of the management process, patient characteristics and follow-up details were noted. Then inquiries reflecting parental perception about terminology were implemented during clinical visits.

Results: In total, 121 patients were evaluated in monthly meetings of the DSD council and 79 inquiries were completed. Fifty-one percent of the families admitted knowing the terms DSD, ambiguous genitalia, “dubious genitals” and intersex. However, only 2% preferred using DSD, 6% intersex and 14% ambiguous genitalia. Fifty-two percent of the parents used a disease name in Latin (mostly hypospadias) addressing the disorder. The offspring of 69% of the parents who were familiar with the name “dubious genitals” were diagnosed in the neonatal period. The preferred terminology used by parents was strongly associated with the terminology used most commonly in the medical speciality their child most often attended.

Conclusion: Each country has its own social norms. We suggest therefore that local committees including medical professionals, patients and families should be employed to develop proper terminology.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.4274/jcrpe.0007DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6083470PMC
July 2018

Effectiveness of Continuous Subcutaneous Insulin Infusion Pump Therapy During Five Years of Treatment on Metabolic Control in Children and Adolescents with Type 1 Diabetes Mellitus

J Clin Res Pediatr Endocrinol 2018 06 28;10(2):147-152. Epub 2018 Feb 28.

Ege University Faculty of Medicine, Department of Pediatric Endocrinology and Diabetes, İzmir, Turkey

Objective: To compare continuous subcutaneous insulin infusion (CSII) therapy with multiple daily insulin (MDI) therapy on metabolic control in children and adolescents with type 1 diabetes mellitus (T1DM) over the long term.

Methods: Fifty-two T1DM patients treated with CSII and monitored for at least one year prior to and at least five years following CSII were included. Thirty-eight age and sex-matched MDI controls with a 5-year follow up were recruited.

Results: Mean age of the subjects, duration of diabetes and CSII therapy were 17.0±4.8 years, 10.7±2.8 years and 7.7±1.5 years respectively. Mean hemoglobin A1c (HbA1c) in the year prior to CSII, during the first year of treatment and after 5 years of CSII were 7.3±1% (56 mmol/mol), 7.0±0.7% (53 mmol/mol) and 7.8±1.3% (62 mmol/mol) respectively. Initial and 5-year mean HbA1C levels of controls were 7.9±1.08% and 8.6±1.8%. Mean HbA1c values were significantly lower in those receiving CSII therapy throughout follow-up. Basal and total insulin doses were significantly lower in the CSII group at all times. HbA1c was compared between subjects by age (0-5, 6-11 and 12-18 years) with no significant difference between them.

Conclusion: Although CSII mean HbA1c values exceeded accepted good metabolic control limits after 5 years, CSII produces better HbA1c control at all times and in all age groups compared to MDI.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.4274/jcrpe.5117DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5985384PMC
June 2018

Analysis of the GCK gene in 79 MODY type 2 patients: A multicenter Turkish study, mutation profile and description of twenty novel mutations.

Gene 2018 Jan 19;641:186-189. Epub 2017 Oct 19.

Department of Medical Genetics, School of Medicine, Ege University, Izmir, Turkey; Division of Pediatric Genetics, Department of Pediatrics, School of Medicine, Ege University, Izmir, Turkey.

Maturity onset diabetes is a genetic form of diabetes mellitus characterized by an early age at onset and several etiologic genes for this form of diabetes have been identified in many patients. Maturity onset diabetes type 2 [MODY2 (#125851)] caused by mutations in the glucokinase gene (GCK). Although its prevalence is not clear, it is estimated that 1%-2% of patients with diabetes have the monogenic form. The aim of this study was to evaluate the molecular spectrum of GCK gene mutations in 177 Turkish MODY type 2 patients. Mutations in the GCK gene were identified in 79 out of 177. All mutant alleles were identified, including 45 different GCK mutations, 20 of which were novel.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.gene.2017.10.057DOI Listing
January 2018

The spectrum of HNF1A gene mutations in patients with MODY 3 phenotype and identification of three novel germline mutations in Turkish Population.

Diabetes Metab Syndr 2017 Nov 31;11 Suppl 1:S491-S496. Epub 2017 Mar 31.

Department of Medical Genetics, Ege University Medical Faculty, Izmir, Turkey.

Background: Maturity-onset diabetes of the young (MODY) is a monogenic form of diabetes mellitus characterized by autosomal dominant inheritance, early age of onset, and pancreatic beta cell dysfunction. Heterozygous mutations in several genes may cause MODY.

Methods: In the present study, we investigated the molecular spectrum of HNF1A (hepatocyte nuclear factor 1a) mutations, in the individuals referred to a reference center for molecular genetic analysis. Mutations screening was performed in a group of 136 unrelated patients (average age 17.22 years) selected by clinical characterization of MODY. Mutation screening involved direct sequencing of the HNF1A gene.

Results: Among 136 individuals analyzed, 10 were carrying heterozygous HNF1A mutations, 3 of them being novel. Clinical features, such as age of diabetes at diagnosis or severity of hyperglycemia, were not related to the mutation type or location. No clear phenotype - genotype correlations were identified.

Conclusions: As a conclusion MODY resulted from HNF1A mutations shows heterogeneity at both phenotypic and molecular levels in Turkish population.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.dsx.2017.03.042DOI Listing
November 2017

Reliability and Validity of the Diabetes Eating Problem Survey in Turkish Children and Adolescents with Type 1 Diabetes Mellitus.

J Clin Res Pediatr Endocrinol 2017 Dec 23;9(4):323-328. Epub 2017 Feb 23.

Ege University Faculty of Medicine, Department of Pediatric Endocrinology, İzmir, Turkey.

Objective: The aim of this study was to show the reliability and validity of a Turkish version of Diabetes Eating Problem Survey-Revised (DEPS-R) in children and adolescents with type 1 diabetes mellitus.

Methods: A total of 200 children and adolescents with type 1 diabetes, ages 9-18 years, completed the DEPS-R Turkish version. In addition to tests of validity, confirmatory factor analysis was conducted to investigate the factor structure of the 16-item Turkish version of DEPS-R.

Results: The Turkish version of DEPS-R demonstrated satisfactory Cronbach's ∝ (0.847) and was significantly correlated with age (r=0.194; p<0.01), hemoglobin A1c levels (r=0.303; p<0.01), and body mass index-standard deviation score (r=0.412; p<0.01) indicating criterion validity. Median DEPS-R scores of Turkish version for the total samples, females, and males were 11.0, 11.5, and 10.5, respectively.

Conclusion: Disturbed eating behaviors and insulin restriction were associated with poor metabolic control. A short, self-administered diabetes-specific screening tool for disordered eating behavior can be used routinely in the clinical care of adolescents with type 1 diabetes. The Turkish version of DEPS-R is a valid screening tool for disordered eating behaviors in type 1 diabetes and it is potentially important to early detect disordered eating behaviors.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.4274/jcrpe.4219DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5785638PMC
December 2017

Association of vitamin D receptor polymorphisms and type 1 diabetes susceptibility in children: a meta-analysis.

Endocr Connect 2017 Apr 23;6(3):159-171. Epub 2017 Feb 23.

Department of Medical GeneticsFaculty of Medicine, Ege University, Bornova, Izmir, Turkey.

Background: There have been studies focused on , I, I and I polymorphisms of the vitamin D receptor (VDR) gene and susceptibility to type 1 diabetes mellitus with controversial results.

Methods: This present study is a meta-analysis investigating the association between FokI, ApaI, TaqI and BsmI polymorphisms of VDR gene and type 1 DM in children. A literature search was performed using Medline, EMBASE, Cochrane and PubMed. Any study was considered eligible for inclusion if at least one of I, I, I and I polymorphisms was determined, and outcome was type 1 DM at pediatric age.

Results: A total of 9 studies comprising 1053 patients and 1017 controls met the study inclusion criteria. The pooled odds ratios (ORs) of the I, I, I and I polymorphisms were combined and calculated. Forest plots and funnel plots of the OR value distributions were drawn. Our meta-analysis has demonstrated statistically significant associations between DM1 and VDR genotypes, IBB ( < 0.05), IBb, ( < 0.05), Ibb ( < 0.05), ITT ( < 0.05) and Itt ( < 0.05) in children.

Conclusion: The results indicated that IBB, IBb and Itt polymorphisms were associated with an increased risk of type 1 DM, whereas Ibb and ITT had protective effect for type 1 DM in children.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1530/EC-16-0110DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5424779PMC
April 2017

Persistent Müllerian Duct Syndrome with Transverse Testicular Ectopia: A Novel Anti-Müllerian Hormone Receptor Mutation.

J Clin Res Pediatr Endocrinol 2017 Jun 17;9(2):179-181. Epub 2017 Jan 17.

Ege University Faculty of Medicine, Department of Pediatric Endocrinology, İzmir, Turkey, E-mail:

Persistent Müllerian duct syndrome is the result of either anti-Müllerian hormone (AMH) deficiency or AMH receptor resistance. A long tubular structure was palpated during the physical examination of a 13-month-old male patient who had presented with bilateral undescended testes. At physical examination, the testes were not palpable. The patient's karyotype was XY, SRY (+), and his AMH level was 22 ng/mol. Structures suggestive of ovaries, a uterus, and fallopian tubes were observed during the laparoscopic examination of the ectopic testis. AMHR2 gene sequence analysis performed with a preliminary diagnosis of AMH receptor resistance revealed a previously unreported homozygous c.24G>A (p.W8X) mutation. The patient was assessed as a case of AMH receptor resistance. Orchiopexy was performed.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.4274/jcrpe.4058DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5463293PMC
June 2017