A Case Series of Three Patients with Cleidocranial Dysplasia: Clinical Presentation and Diagnostic Considerations.

Cleidocranial dysplasia (CCD) is a rare genetic condition that affects the bones and teeth. In our study, we presented three cases of CCD, including one with a new mutation and two with a family history. Case 1 had a unique heterozygous frameshift mutation (NM_001015051,c.762del, p.(Ser256Valfs*2)), while Case 2 and her brother (Case 3) had a common pathogenic missense mutation (NM_001015051,c.674G, p.Arg225Gln), which was also found in their father. The mutation in Case 1 was not reported before. Interestingly, the symptoms in Case 1, with the new mutation, were less severe than the other cases and the previous reports.

The comparison of two mealtime insulin dosing algorithms for high and low glycaemic index meals in adolescents with type 1 diabetes.

AIMS: Postprandial glycaemic variability carries on being a clinical challenge in optimizing glucose control in type 1 diabetes. The aim of this study was to compare the postprandial glycaemic effects of carbohydrate counting and food insulin index algorithms following the consumption of protein-rich, high-fat meals with different glycaemic index (GI) in adolescents with type 1 diabetes. METHODS: A randomized, single-blind and crossover trial included 15 adolescents aged 14-18 years with type 1 diabetes. Participants consumed two different test meals with similar energy, macronutrients and food insulin index but the approximately twofold difference in GI, in random order on four consecutive mornings at their home. Insulin dose for high- and low-GI test meals was determined by using the carbohydrate counting and food insulin index algorithms. Four-hour postprandial glycaemia was assessed by the continuous glucose monitoring system. RESULTS: Compared with carbohydrate counting, the food insulin index algorithm significantly decreased peak glucose excursion (-57%, p = 0.02), incremental area under the curve (-65%, p = 0.02) and coefficient variation of blood glucose (-37%, p = 0.03) in the high-GI meal, though there was no difference between the two algorithms in the low-GI meal. The occurrence of hypoglycaemia did not significantly differ between insulin dosing algorithms for the high-GI (p = 0.58) and low-GI (p = 0.20) meals. CONCLUSIONS: The food insulin index algorithm may be beneficial for postprandial glycaemic control after the consumption of high-GI meals in adolescents with type 1 diabetes.

A comparison of emotional eating, social anxiety and parental attitude among adolescents with obesity and healthy: A case-control study.

This case-controlled study was conducted to determine and compare the emotional eating, social anxiety and parental attitude in those adolescents with obesity and healthy counterparts. The sample of the study consist of obese adolescents in 14-18 aged (n = 150) followed up in the pediatric endocrinology outpatient clinic of a tertiary hospital and healthy adolescents in 14-18 aged (n = 150) who were studying in high schools. The data were collected using a questionnaire form, Emotional Eating Scale Adapted to Use in Children and Adolescents (EES-C), Social Anxiety Scale for Children-Revised (SASC-R) and Parenting Style Scale (PSS). The SASC-R and EES-C mean scores of obese adolescents were 39.03 ± 13.09 (p ≤ 0.001) and 76.66 ± 16.30 (p ≤ 0.001), respectively. The mean scores of PSS-AI, PSS-SS and PSS-PA subscales in obese adolescents were 26.80 ± 4.42 (p ≤ 0.001), 28.14 ± 4.06 (p ≤ 0.001) and 22.32 ± 4.63 (p = 0.037), respectively. There was a low-level correlation between the EES-C and SASC-R mean scores of obese adolescents (p < 0.05). The mean scores of PSS-AI, PSS-SS and PSS-PA subscales of PSS with EES-C and SASC-R of obese adolescents were no correlated (p > 0.05). In this study, the mean scores of the emotional eating and social anxiety of obese adolescents were higher than healthy ones. There was a low level of positive correlation between emotional eating and social anxiety mean scores of obese adolescents.

The molecular basis and genotype-phenotype correlations of congenital adrenal hyperplasia (CAH) in Anatolian population.

Congenital adrenal hyperplasia (CAH) is an autosomal recessive genetic disorder due to presence of mutations in the genes involved in the metabolism of steroid hormones in adrenal gland. There are two main forms of CAH, classic form and non-classic form. While classic form stands for the severe form, the non-classic form stands for the moderate and more frequent form of CAH. The enzyme deficiencies such as 21-hydroxylase, 11-beta-hydroxylase, 3-beta-hydroxysteroid dehydrogenase, 17-alpha-hydroxylase deficiencies are associated with CAH. In this study, we aimed to investigate CYP21A2, CYP11B1, HSD3B2 genes which are associated with 21-hydroxylase, 11-beta-hydroxylase and 3-beta-hydroxysteroid dehydrogenase enzyme deficiencies, respectively, in 365 individuals by using Sanger sequencing method. We emphasized the classification of variants according their disease causing potential, and evaluated variants' frequencies including newly discovered novel variants. As a result, 32 variants of CYP21A2 including 10 novel variants, 9 variants of CYP11B1 including 3 novel variants and 6 variants of HSD3B2 including 4 novel variants were identified. The conclusions of our study showed that in Anatolia, discovery of novel variants is quite common on account of tremendous ratios of consanguineous marriages which increases the frequency of CAH. These results will contribute to the understanding of molecular pathology of the disease.

A potential serious complication in infants with congenital obstructive uropathy: Secondary pseudohypoaldosteronism.

Patients who have secondary pseudohypoaldosteronism (PHA) in addition to hyponatraemia, hyperpotassaemia and high serum aldosterone levels for the age were included in this retrospective study.Among eight patients, seven patients were diagnosed with PHA secondary to obstructive uropathy (OUP), whereas one patient had PHA secondary to ileostomy. Six patients with OUP had simultaneous urinary tract infection (UTI) and in all except one patient, secondary PHA recovered with only UTI treatment before applying surgical correction. All the patients were younger than 3 months age. In three patients with PUV diagnosis, salt wasting recurred in an UTI episode under 3 months of age.

Permanent neonatal diabetes mellitus and neurological abnormalities due to a novel homozygous missense mutation in NEUROD1.

The basic helix-loop-helix (bHLH) transcription factor, neuronal differentiation 1 (NEUROD1) (also known as BETA2) is involved in the development of neural elements and endocrine pancreas. Less than 10 reports of adult-onset non-insulin-dependent diabetes mellitus (NIDDM) due to heterozygous NEUROD1 mutations and 2 cases with permanent neonatal diabetes mellitus (PNDM) and neurological abnormalities due to homozygous NEUROD1 mutations have been published. A 13 year-old female was referred to endocrine department due to hyperglycemia. She was on insulin therapy following a diagnosis of neonatal diabetes mellitus (NDM) at the age of 9-weeks but missed regular follow-up. Parents are second cousin. There was a significant family history of adult onset NIDDM including patient's father. Auxological measurements were within normal ranges. On laboratory examination blood glucose was 33.2 mmol/L with undetectable c-peptide and glycosylated hemoglobin level of 8.9% (73.8 mmol/mol). She had developed difficulty in walking at the age of 4 years which had worsened over time. On further evaluation, a diagnosis of visual impairment, mental retardation, ataxic gait, retinitis pigmentosa and sensory-neural deafness were considered. Cranial magnetic resonance imaging revealed cerebellar hypoplasia. Molecular genetic analysis using targeted next generation sequencing detected a novel homozygous missense mutation, p.Ile150Asn(c.449T>A), in NEUROD1. Both parents and 2 unaffected siblings were heterozygous for the mutation. We report the third case of PNDM with neurological abnormalities caused by homozygous NEUROD1 mutation, the first caused by a missense mutation. Heterozygous carriers of the p.Ile150Asn mutation were either unaffected or diagnosed with diabetes in adulthood. It is currently unclear whether the NEUROD1 heterozygous mutation has contributed to diabetes development in these individuals.

Scrotal hair in infancy: A case series.

Scrotal hair is a clinical condition that occurs rarely in infancy. Its prevalence is not known. We present a retrospective analysis of six patients referred to our pediatric endocrinology clinic. Except for scrotal hair development, all physical examinations were normal. Underlying pathologic hyperandrogenism was excluded in each case. Clinical regression was observed in all four infants with documented follow-up visits. Scrotal hair in infancy is not well known to most pediatricians and dermatologists and can cause parental anxiety. Our cases are typical of the benign course of isolated scrotal hair.

Neonatal Endocrinologic Problems in Collodion Babies.

OBJECTIVES: To identify endocrinologic problems, particularly those concerning growth, in collodion babies (CBs). METHODS: Clinically identified newborn CBs were included in the study group (group 1). Because CBs are generally born premature, small for gestational age (SGA), or both, a control group matched to the study group in terms of gestational age and birthweight (group 2) was also established. Blood specimens were collected from both groups for thyroid function tests and to measure serum growth hormone (GH), insulinlike growth factor 1 (IGF-1) and IGF binding protein-3 (IGFBP-3) levels. RESULTS: Group 1 consisted of 42 CBs (25 male, 17 female) with gestational ages of 32 to 42 weeks and birthweights of 1,400 to 4,000 g. Twelve were assessed as premature and 17 as SGA. Serum IGF-1 and IGFBP-3 levels were lower and serum GH levels higher than in controls. Primary hypothyroidism was diagnosed in 10 patients in the study group, subclinical hypothyroidism in 2, and central hypothyroidism in 1. A statistically significant difference was determined between the groups in terms of primary hypothyroidism (p = 0.01). Serum GH levels were weakly negatively correlated with birthweight (correlation coefficient [r] = -0.32, p = 0.04) and serum IGF-1 (r = -0.38, p = 0.001) and IGFBP-3 (r = -0.36, p = 0.002) levels. CONCLUSION: Premature birth and SGA are common in CBs. GH levels are high and IGF-1 and IGFBP-3 levels low at birth as a sign of GH resistance in these patients. The greater prevalence of hypothyroidism in these children is also significant.

Prospective investigation of anterior pituitary function in the acute phase and 12 months after pediatric traumatic brain injury.

PURPOSE: Although head trauma is common in childhood, there is no enough prospective study investigating both acute phase and 12 months after injury. Therefore, a prospective clinical trial was planned to evaluate the pituitary function in childhood in the acute and chronic phase after traumatic brain injury (TBI). METHODS: Forty-one children (27 boys and 14 girls, mean age 7 ± 4.3), who were admitted to neurosurgery intensive care unit due to head trauma, were included. Twenty-one (51.2 %) patients had mild, 10 (24.4 %) had moderate, and 10 (24.4 %) had severe TBI. Twenty-two of them were reevaluated 12 months after TBI. Basal pituitary hormone levels were measured during acute (first 24 h) and chronic phase of TBI. Additionally, in the chronic phase, GHRH-arginine test was used for the diagnosis of growth hormone (GH) deficiency. RESULTS: In the acute phase, 10 patients (24.4 %) had ACTH deficiency, and the overall 44.3 % of patients had at least one pituitary hormone dysfunction. All the pituitary hormone deficiencies during the acute phase were recovered after 12 months. Two patients (9.1 %) had new-onset GH deficiency in the chronic phase, and in one of them, ACTH deficiency was also present. CONCLUSIONS: Present prospective data clearly demonstrated that most of the hormonal changes in the early acute phase were transient, suggesting an adaptive response, and these changes did not predict the hormone deficiencies after 1 year. In the chronic phase, although GH deficiency was present, the frequency of TBI-induced hypopituitarism was clearly lower than the adult patients.

Eating Disorders and Sleep Disturbance as Determinants of Metabolic Control in Adolescents with Type 1 Diabetes.

This cross-sectional study examined the effect of sleep disturbance and eating disorders on metabolic control in adolescents with Type 1 Diabetes. The study was conducted with adolescents with T1DM treated at a university hospital in Turkey between October 2023 and January 2024. The study sample consisted of 120 adolescents with T1DM between the ages of 10-18. Data were collected online using the Adolescent Information Form, Dutch Eating Behavior Questionnaire (DEBQ), and DSM-5 Sleep Disorder Scale (SDS). Mean, percentage, and regression analyses were used to analyze the data. Ethics committee, institutional permission and written permission from the adolescents with Type 1 Diabetes and their parents were obtained for the study. In the current study, sleep disturbance and eating disorders explained 38.5% and 40.2% of HbA1c, respectively, and were found to have a significant effect (respectively: F = 73.737, p ≤ .001; F = 19.353, p ≤ .001). This study provides evidence that eating disorders and sleep disturbance explain approximately half of HbA1c. The results of the study revealed that sleep disturbance and eating disorders were significant predictors of metabolic control in adolescents with type 1 diabetes.

Congenital Adrenal Hyperplasia with Combined 21-hydroxylase deficiency and 17α-hydroxylase/17,20-lyase deficiency: An undervirilized male.

21-hydroxylase deficiency stands as the most prevalent form of congenital adrenal hyperplasia, primarily resulting from mutations in the CYP21A2 gene. On the other hand, mutations within the CYP17A1 gene lead to 17α-hydroxylase/17,20-lyase enzyme deficiencies. The scarcity of 17-OH deficiency is noteworthy, accounting for less than 1% of all congenital adrenal hyperplasia cases. The male patient, born from a first-degree cousin marriage, exhibited several symptoms, including left undescended testis, micropenis, penile chord, left sensorineural hearing loss, and gynecomastia. He reported micropenis as a concern at the age of 13.5 years. His hormone profile revealed high levels of serum 17-hydroxyprogesterone, progesterone, and pregnenolone. In this case with a 46 XY karyotype, suspicions arose regarding Cytochrome P450 oxidoreductase deficiency due to ambiguous genitalia and an atypical hormone profile. Analysis unveiled two distinct homozygous and pathogenic variants in the CYP21A2 and CYP17A1 genes. Notably, mineralocorticoid precursors escalated, while cortisol and sex steroid precursors decreased during the high (250 mcg) dose ACTH stimulation test. The mutation c.1169C > G (p.Thr390Arg) in CYP17A1, which is the second documented case in literature, stands out due to its unique set of accompanying features. Mutations occurring in CYP21A2 and CYP17A1 result in complete or partial enzyme deficiencies, and the detection of homozygous mutations in two different enzyme systems within the steroidogenic pathway is noteworthy.

Adherence to Growth Hormone Treatment in Children During COVID-19 Pandemic

Objective: Treatment adherence is crucial for the success of growth hormone (GH) therapy. Reported nonadherence rates in GH treatment have varied widely. Several factors may have an impact on adherence. Apart from these factors, the global impact of the COVID-19 pandemic, including problems with hospital admission and routine follow-up of patients using GH treatment, may have additionally affected the adherence rate. The primary objective of this study was to investigate adherence to treatment in patients receiving GH. In addition, potential problems with GH treatment during the pandemic were investigated. Materials and Methods: This was a multicenter survey study that was sent to pediatric endocrinologists in pandemic period (June 2021-December 2021). Patient data, diagnosis, history of pituitary surgery, current GH doses, duration of GH therapy, the person administering therapy (either parent/patient), duration of missed doses, reasons for missed doses, as well as problems associated with GH therapy, and missed dose data and the causes in the recent year (after the onset of the pandemic) were queried. Treatment adherence was categorized based on missed dose rates over the past month (0 to 5%, full adherence; 5.1 to 10% moderate adherence; >10% nonadherence). Results: The study cohort consisted of 427 cases (56.2% male) from thirteen centers. Median age of diagnosis was 8.13 (0.13-16) years. Treatment indications were isolated GH deficiency (61.4%), multiple pituitary hormone deficiency (14%), Turner syndrome (7.5%), idiopathic GH deficiency (7.5%), small for gestational age (2.8%), and "others" (6.8%). GH therapy was administered by parents in 70% and by patients in 30%. Mean daily dose was 32.3 mcg/kg, the annual growth rate was 1.15 SDS (min -2.74, max 9.3). Overall GH adherence rate was good in 70.3%, moderate in 14.7%, and poor in 15% of the patients. The reasons for nonadherence were mainly due to forgetfulness, being tired, inability to access medication, and/or pen problems. It was noteworthy that there was a negative effect on adherence during the COVID-19 pandemic reported by 22% of patients and the main reasons given were problems obtaining an appointment, taking the medication, and anxiety about going to hospital. There was no difference between genders in the adherence rate. Nonadherence to GH treatment decreased significantly when the patient: administered the treatment; was older; had longer duration of treatment; and during the pandemic. There was a non-significant decrease in annual growth rate as nonadherence rate increased. Conclusion: During the COVID-19 pandemic, the poor adherence rate was 15%, and duration of GH therapy and older age were important factors. There was a negative effect on adherence during the pandemic period.

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.

Waist circumference percentiles among Turkish children under the age of 6 years.

Waist circumference, a proxy measure of abdominal obesity, is associated with cardio-metabolic risk factors in childhood and adolescence. Although there are numerous studies about waist circumference percentiles in children, only a few studies cover preschool children. The aim of this study was to develop age- and gender-specific waist circumference smoothed reference curves in Turkish preschool children to determine abdominal obesity prevalence and to compare them with reference curves obtained from different countries. The design of the study was cross-sectional. A total of 2,947 children (1,471 boys and 1,476 girls) aged 0-6 years were included in the study. The subjects were divided according to their gender. Waist circumference was measured by using a standardized procedure. The age- and gender-specific waist circumference reference curves were constructed and smoothed with LMS method. The reference values of waist circumference, including 3rd, 10th 25th, 50th, 75th, 90th, and 97th percentiles, and standard deviations were given for preschool children. Waist circumference values increased with age, and there were differences between genders. The prevalence of abdominal obesity was calculated as 10.1 % for boys and 10.7 % for girls. Having compared our data with two other countries' data, we found that our waist circumference data were significantly lower. This is the first cross-sectional study for age- and gender-specific references of 0- to 6-year-old Turkish children. The gender- and age-specific waist circumference percentiles can be used to determine the risk of central obesity.

Change in waist circumference over 3 years in Turkish children and adolescents.

AIM: To observe change in waist circumference (WC) over 3 years in children and adolescents and to compare these data with local and international references. SUBJECTS AND METHODS: The data of the second study determining the anthropometric measurements of Turkish children and adolescents (DAMTCA-II) were used to calculate WC percentiles. A total of 4234 children and adolescents aged 6-17 years (1890 boys and 2344 girls) were enrolled. The 3rd, 5th, 10th, 25th, 50th, 75th, 85th, 90th, 95th and 97th percentiles and z-scores were computed by the LMS Method. RESULTS: The mean WC was significantly higher in boys than in girls in 12.5, 13 and 15-17 year old children (p < 0.001). The prevalence of central obesity (WC ≥ 90th percentile) was 13.5% (14.3% in boys and 12.9% in girls, respectively). There was no significant difference in prevalence of abdominal obesity, between each gender (p = 0.179) and age group from 6-17 years (p = 0.590). In a comparison with the available contemporary international references, the 50th percentiles of these references were similar to those in Bulgaria, but markedly higher than those of Malaysian children and of Chinese children living in Hong Kong. CONCLUSIONS: The prominent finding of this study was the significant increase in WC percentiles in a short time in both genders. In addition, the WC references are similar to other regional references, but significantly higher than those of East Asia.

Mannose-binding lectin (MBL) levels in children with Hashimoto's thyroiditis.

OBJECTIVE: Hashimoto's thyroiditis (HT) was described many years ago, but the etiopathogenesis remains unclear. Mannose-binding lectin (MBL) initiates complement activation in the lectin pathway. We determined MBL levels in children with HT and the associations thereof with thyroid hormone and thyroid autoantibody levels. METHODS: Thirty-nine patients with HT and 41 controls were enrolled from the pediatric outpatient clinics. Subjects were grouped according to their thyroid functions: Euthyroid, marked hypothyroidism and clinical/subclinical hyperthyroidism. MBL levels were compared among these groups. Serum MBL levels of the subjects were determined using MBL Human ELISA kit. RESULTS: Serum MBL levels were studied in serum samples from the 80 subjects (48 (60.0%) females). MBL levels in HT and control groups were 50.787±34.718 and 50.593±44.28 ng/ml (p=0,983), respectively. In HT group, there was no significant difference in MBL levels between thyroid function groups (p=0.869). In addition, gender was not detected as a factor for serum MBL levels. Also we found negative correlation between WBC and serum MBL levels (r=-0.532; p=0.050). Otherwise there was no correlation between TSH, anti-TPO and anti-TG with serum MBL levels. CONCLUSION: MBL levels did not decrease in HT patients. Further research is needed to elucidate more fully any role for MBL in the development of autoimmune thyroid disease.

Triponderal mass index is as strong as body mass index in the determination of obesity and adiposity.

OBJECTIVE: In determining obesity and body adiposity, triponderal mass index (TMI) is as strong an anthropometric measurement as body mass index (BMI). The aim of this study was to develop TMI reference values for Turkish children and adolescents and compare TMI with BMI according to body adiposity and obesity indices. METHODS: Data from the DAMTCA-II (Determination of Anthropometric Measurements of Turkish Children and Adolescents II) study were used in this cross-sectional study. Data from 4330 children (1931 boys, 2399 girls) ages 6 to 17 y were evaluated, and the TMI percentile values were produced. The predictive power of TMI and BMI for obesity and overweight were done for waist circumference, waist/height ratio, body fat percentage, and upper arm fat area, which are different parameters used to determine body adiposity. RESULTS: The 3rd, 5th, 10th, 25th, 50th, 75th, 85th, 90th, 95th, and 97th TMI percentiles and mean values were calculated for all children's age and sex. TMI cutoff values were calculated by receiver operating characteristic analysis regarding waist/height ratio 0.5, waist circumference ≥90 percentile, arm fat area ≥85 percentile, and body fat percentage ≥85. TMI and BMI area under the curve values were similar for each of these four measurements. TMI was as robust an index as BMI in demonstrating obesity and adiposity for all age groups in boys and girls. It was concluded that the values >90th percentile (median 15.8 kg/m3) in girls aged ≤10 y, 95th percentile (median 16.2 kg/m3) in girls aged >10 y, >85th percentile (median 14.9 kg/m3) in boys aged ≤12 y and 75th percentile (median value 14.5 kg/m3) in boys aged >12 y are critical values for TMI when evaluating adiposity and obesity. CONCLUSIONS: We considered that TMI is as effective as BMI in terms of waist/height ratio, waist circumference, arm fat area, and body fat percentage in determining overweight and obesity in children. The ages at which TMI showed distinct variation were determined for both sexes.

A Case of Short Stature Caused by a Mutation in the ACAN Gene.

Introduction: Aggrecanopathies are rare disorders associated with idiopathic short stature. They are caused by pathogenic changes in the ACAN gene located on chromosome 15q26. In this study, we present a case of short stature caused by mutations in the ACAN gene. Case Presentation: A 3-year-3-month-old male patient was referred to us because of his short stature. Physical examination revealed proportional short stature, frontal bossing, macrocephaly, midface hypoplasia, ptosis in the right eye, and wide toes. When the patient was 6 years and 3 months old, his bone age was compatible with 7 years of age. The patient underwent clinical exome sequencing and a heterozygous nonsense c.1243G>T, p.(Glu415*) pathogenic variant was detected in the ACAN gene. The same variant was found in his phenotypically similar father. Our patient is the second case with ptosis. Discussion: ACAN gene mutation should be considered in the differential diagnosis of patients with idiopathic short stature. The development and widespread use of next-generation sequencing technology has increased the diagnostic and treatment possibilities.

Neck circumference as a novel parameter to determine metabolic risk factors in obese children.

BACKGROUND: To establish the association between neck circumference and cardiometabolic risk factors and to determine the utility of the neck circumference as a parameter in predicting children at cardiometabolic risk. MATERIALS AND METHODS: Five - hundred and eighty-one children (461: overweight/obese, 120: normal body mass index) aged between 5 and 18 years were enrolled. Neck circumference, waist circumference, blood pressure and fasting plasma glucose, insulin, total cholesterol, triglyceride and high-density lipoprotein (HDL) cholesterol were recorded, and the homeostasis model assessment for insulin resistance score was calculated. RESULTS: Neck circumference was negatively correlated with HDL cholesterol and positively correlated with all other parameters, with the exception of fasting plasma glucose in pubertal boys and girls and total cholesterol in pubertal girls. Linear regression analysis by designating neck circumference as a dependent variable revealed that insulin and TG levels in prepubertal boys and blood pressure and TG levels in pubertal boys were positively correlated with neck circumference. We found that diastolic blood pressure and insulin were positively correlated, while HDL levels were negatively correlated with neck circumference in prepubertal girls. Systolic blood pressure and insulin were positively correlated with neck circumference in pubertal girls. The cut-off value for neck circumference, as an indicator for metabolic syndrome (MS), was calculated as 36 cm in boys and 35 cm in girls. CONCLUSIONS: Neck circumference measurement was shown to be associated with cardiometabolic risk factors in children. We suggest the use of neck circumference as a novel, simple, practical and reliable anthropometric index in predicting children at risk for cardiometabolic diseases.

The absence of insulin resistance in metabolic syndrome definition leads to underdiagnosing of metabolic risk in obese patients.

This study explores in a group of obese children and adolescents aged 10 to 16 years, the prevalence of metabolic syndrome (MS) according to the criteria of International Diabetes Federation (IDF). In addition, the prevalence of insulin resistance (IR) was investigated to find correlations between MS and IR. IDF definition was compared to a modified WHO definition. A total of 159 obese patients (74 male and 85 female; median age 12.7 years) were included in the study. Anthropometric measurements, blood pressure, and serum fasting lipids were evaluated. An oral glucose tolerance test (OGTT) was performed, and serum glucose and insulin levels were measured at 0, 30, 60, 90, and 120 min. Homeostasis model assessment of insulin resistance (HOMA-IR), quantitative insulin sensitivity check index (QUICKI), fasting glucose/insulin ratio (FGIR), Matsuda index, and total insulin levels during OGTT were calculated. For the IR diagnosis, we used cutoff values described in previous publications (HOMA-IR of >3.16, QUICKI of <0.357, FGIR of <7, and/or the sum of insulin levels during OGTT of >300 mIU/mL). MS prevalence, defined according to IDF criteria, was 34.6 %. Using the IDF definition, there was no statistically significant difference for the surrogate IR indices between patients with or without MS (QUICKI, 94.5 vs. 83.7 %), FGIR (81.1 vs. 78.8 %), HOMA-IR (70.9 vs. 63.5 %), and total insulin levels during OGTT (61.8 vs. 51.9 %). The Matsuda index values, the prevalence of fasting hyperinsulinemia, and impaired glucose tolerance were also similar in these two groups. In conclusion, IR was prominent in obese patients with and without MS. IDF definition of MS fails to discover individuals with IR, unless it is specifically investigated.