17α Hydroxylase/17,20 lyase deficiency: clinical features and genetic insights from a large Turkey cohort.

PURPOSE: 17α Hydroxylase/17,20 lyase deficiency (17OHD) is a rare form of congenital adrenal hyperplasia, typically diagnosed in late adolescence with symptoms of pubertal delay and hypertension. This study aimed to determine the clinical and laboratory characteristics of 17OHD cases and gather data on disease management. METHODS: Data from 97 nationwide cases were analyzed using the CEDD-NET web system. Diagnostic, follow-up findings, and final heights of patients were evaluated. RESULTS: Mean age at admission was 13.54 ± 4.71 years, with delayed puberty as the most common complaint. Hypertension was detected in 65% at presentation; hypokalemia was present in 34%. Genetic analysis revealed Exon 1-6 homozygous deletion as the most frequent mutation, identified in 42 cases. Hydrocortisone replacement was universal; pubertal replacement was administered to 66 cases. Antihypertensive treatment was required in 57 (90%) patients. Thirty-seven cases reached final height, with an average SD of 0.015 in 46,XX and -1.43 in 46,XY. Thelarche and pubarche did not develop properly in some cases despite estradiol treatment. CONCLUSION: This study represents the largest cohort of pediatric cases of 17-hydroxylase deficiency (17OHD) documented in the literature. Hypertension and hypokalemia can serve as guiding indicators for early diagnosis.The final height is typically considered to be normal. The relationship between genotype and phenotype remains elusive. The initial genetic test for exon 1-6 deletions may be MLPA in our region.

Osteogenesis Imperfecta and Split Foot Malformation due to 7q21.2q21.3 Deletion Including COL1A2, DLX5/6 Genes: Review of the Literature.

Copy number variation in loss of 7q21 is a genetic disorder characterized by split hand/foot malformation, hearing loss, developmental delay, myoclonus, dystonia, joint laxity, and psychiatric disorders. Osteogenesis imperfecta caused by whole gene deletions of COL1A2 is a very rare condition. We report a Turkish girl with ectrodactyly, joint laxity, multiple bone fractures, blue sclera, early teeth decay, mild learning disability, and depression. A copy number variant in loss of 4.8 Mb at chromosome 7 (q21.2q21.3) included the 58 genes including DLX5, DLX6, DYNC1I1, SLC25A13, SGCE, and COL1A2 . They were identified by chromosomal microarray analysis. We compared the findings in our patients with those previously reported. This case report highlights the importance of using microarray to identify the genetic etiology in patients with ectrodactyly and osteogenesis imperfecta.

Clinical and Laboratory Characteristics of MODY (Maturity Onset Diabetes of Young) Cases, Genetic Mutation Spectrum and Phenotype-genotype Relationship.

Objective: Maturity-onset diabetes of the young (MODY) occurs due to mutations in genes involved in pancreatic beta cell function and insulin secretion, has heterogeneous clinical and laboratory features, and account for 1-5% of all diabetes cases. The prevalence and distribution of MODY subtypes vary between countries. The aim of this study was to evaluate the clinical and laboratory characteristics, mutation distribution, and phenotype-genotype relationship in a large case series of pediatric Turkish patients genetically diagnosed with MODY. Methods: MODY cases from 14 different pediatric endocrinology departments were included. Diagnosis, treatment, follow-up data, and results of genetic analysis were evaluated. Results: A total of 224 patients were included, of whom 101 (45%) were female, and the mean age at diagnosis was 9.4±4.1 years. Gene variant distribution was: 146 (65%) GCK; 43 (19%) HNF1A; 8 (3.6%) HNF4A, 8 (3.6%) KLF11 and 7 (3.1%) HNF1B. The remaining 12 variants were: PDX (n=1), NEUROD1 (n=3), CEL (n=1), INS (n=3), ABCC8 (n=3) and KJNC11 (n=1). Of the cases, 197 (87.9%) were diagnosed with incidental hyperglycemia, 16 with ketosis (7%) and 7 (3%) with diabetic ketoacidosis (DKA), while 30% presented with classical symptoms of diabetes. Two-hundred (89%) had a family history of diabetes. Anti-GAD antibody was detected in 13 cases, anti-islet antibody in eight and anti-insulin antibody in four. Obesity was present in 16. Distribution of therapy was: 158 (71%) diet only; 23 (11%) intensive insulin treatment; 17 (7.6%) sulfonylureas; 10 (4.5%) metformin; and 6 (2.7%) insulin and oral antidiabetic treatment. Conclusion: This was the largest genetically diagnosed series from Turkey. The most common gene variants were GCK and HNF1A with much lower proportions for other MODY types. Hyperglycemia was the most common presenting symptom while 11% of patients had diabetes-associated autoantibodies and 7% were obese. The majority of patients received dietary management only.

The relationship between blood biochemical parameters and oral health in children with obesity/overweight.

Aim The purpose of this study was to evaluate the effects of obesity and overweight on the oral/dental health and blood biochemistry parameters in children.Methods A total of 87 children (29 boys, 58 girls) aged 1-18 presenting to our paediatric endocrinology outpatient clinic were included in the study. The patient group consisted of children with obesity/overweight and the control group consisted of children with normal weight. Paediatric patients were examined simultaneously by a paediatrician and a paediatric dentist. Oral/dental health examinations of all children included in the study were performed by a specialist paediatric dentist and dmft/DMFT (decayed, missing and filled teeth) values were calculated separately in the mixed dentition period. The Community Periodontal Index of Treatment Needs 23 index and the dental plaque 35 index were evaluated at oral/dental health examinations. Oral and dental health examination findings and blood biochemistry parameters were compared between the two groups.Results While DMFT, dental plaque index, blood c-reactive protein (CRP) and parathyroid hormone (PTH) levels were significantly increased in children with overweight/obesity compared to children with normal weight, there was no difference in terms of daily toothbrushing habits and last dental examination times. Overweight/obesity was found to be associated with the dental plaque and DMFT/dmft index, and elevation in the blood biochemistry parameters CRP and PTH among the children in this study.Conclusion The observation of significant elevation in DMFT and dental plaque indices and numbers of filled deciduous teeth showed that oral/dental health problems and dental decay may emerge more frequently in children with overweight/obesity. Children with overweight should be routinely provided with dental care as part of a multidisciplinary team that includes paediatricians and dentists.

Effects of childhood obesity on ocular pulse amplitude and intraocular pressure / Efeitos da obesidade infantil na amplitude do pulso ocular e na pressão intraocular

ABSTRACT Purpose: To assess intraocular pressure and ocular pulse amplitude changes in obese children and adolescents using dynamic contour tonometry. Methods: 137 cases, 64 obese and 73 healthy children, who were both age-matched and gender-matched, comprised the study population in this cross-sectional study. Children with body mass index values >95% for sex and age were regarded as obese. Participants underwent detailed ophthalmological examinations, including intraocular pressure measurement using a Pascal dynamic contour tonometer. Relationships between intraocular pressure and ocular pulse amplitude measurements and age, sex, obesity, pubertal status, and insulin resistance were investigated. Results: Bilateral ocular pulse amplitude was lower while intraocular pressure was higher in the obese group than in the control group (p<0.001). No significant relationship was observed between insulin resistance and intraocular pressure or ocular pulse amplitude (p>0.005). No correlation was determined between systolic and diastolic blood pressure, homeostasis model assessment for insulin resistance, or blood lipid levels and intraocular pressure and ocular pulse amplitude. Conclusion: Our results show that obesity caused an increase in intraocular pressure and a decrease in ocular pulse amplitude independently of insulin resistance in children and adolescents. Prospective studies involving long-term follow-up of cases are now needed to assess the probable adverse effects of these ocular findings in obese children.

RESUMO Objetivo: Avaliar a pressão intraocular e as alterações da amplitude do pulso ocular em crianças e adolescentes obesos, usando tonometria de contorno dinâmico. Métodos: Um total de 137 casos, sendo 64 crianças obesas e 73 crianças saudáveis, pareadas por idade e sexo, compôs a população estudada neste estudo transversal. Crianças com valores de índice de massa corporal superior ao percentil de 95% para seu sexo e idade foram consideradas obesas. Os participantes foram submetidos a exames oftalmológicos detalhados, incluindo a medição da pressão intraocular com um tonômetro de contorno dinâmico Pascal. As relações entre a pressão intraocular e as medidas da amplitude do pulso ocular com a idade, sexo, obesidade, estado puberal e resistência à insulina foram investigadas. Resultados: A amplitude do pulso ocular bilateral foi menor no grupo obeso do que no grupo controle saudável (p<0,001), enquanto a pressão intraocular foi maior (p<0,001). Não foi observada nenhuma relação significativa entre a resistência à insulina e a pressão intraocular ou a amplitude de pulso ocular (p>0,005). Não foi determinada nenhuma correlação entre a pressão arterial sistólica e diastólica, a avaliação do modelo de homeostase para resistência à insulina ou os níveis de lipídios sanguíneos e a pressão intraocular e a amplitude de pulso ocular. Conclusão: Os resultados mostraram que a obesidade causou um aumento da pressão intraocular e uma diminuição da amplitude do pulso ocular em crianças e adolescentes, independentemente da resistência à insulina. São necessários agora estudos prospectivos envolvendo o seguimento de longo prazo dos casos, para avaliar os prováveis efeitos adversos desses achados oculares observados em crianças obesas.