Sezer Acar

The Relationship between Serum Zonulin Level and Clinical and Laboratory Parameters of Childhood Obesity

Objective: To investigate the relationship between zonulin levels and clinical and laboratory parameters of childhood obesity. Methods: The study included obese children with a body mass index (BMI) >95th percentile and healthy children who were of similar age and gender distribution. Clinical (BMI, waist circumferences, mid-arm circumference, triceps skinfold, percentage of body fat, systolic blood pressure, diastolic blood pressure) and biochemical (glucose, insulin, lipid levels, thyroid function tests, cortisol, zonulin and leptin levels) parameters were measured. Results: A total of 43 obese subjects (23 males, mean age: 11.1±3.1 years) and 37 healthy subjects (18 males, mean age: 11.5±3.5 years) were included in this study. Obese children had significantly higher insulin, homeostasis model assessment of insulin resistance, triglyceride, total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol (HDL-C), zonulin and leptin levels than healthy children (p<0.05), while glucose levels were not different (p>0.05). Comparison of the obese children with and without insulin resistance showed no statistically significant differences for zonulin levels (p>0.05). Zonulin levels were found to negatively correlate with HDL-C and positively correlate with leptin levels, after adjusting for age and BMI. Conclusion: To the best of our knowledge, this is the first study investigating the relationship between circulating zonulin level (as a marker of intestinal permeability) and insulin resistance and leptin (as markers of metabolic disturbances associated with obesity) in childhood obesity. The results showed that zonulin was significantly higher in obese children when compared to healthy children, a finding indicating a potential role of zonulin in the etiopathogenesis of obesity and related disturbances.

Clinical and genetic characteristics of 15 families with hereditary hypophosphatemia: Novel Mutations in PHEX and SLC34A3

Background Hereditary hypophosphatemia is a group of rare renal phosphate wasting disorders. The diagnosis is based on clinical, radiological, and biochemical features, and may require genetic testing to be confirmed. Methodology Clinical features and mutation spectrum were investigated in patients with hereditary hypophosphatemia. Genomic DNA of 23 patients from 15 unrelated families were screened sequentially by PCR-sequencing analysis for mutations in the following genes: PHEX, FGF23, DMP1, ENPP1, CLCN5, SLC34A3 and SLC34A1. CytoScan HD Array was used to identify large deletions. Results Genetic evaluation resulted in the identification of an additional asymptomatic but intermittent hypophosphatemic subject. Mutations were detected in 21 patients and an asymptomatic sibling from 13 families (86.6%, 13/15). PHEX mutations were identified in 20 patients from 12 families. Six of them were novel mutations present in 9 patients: c.983_987dupCTACC, c.1586+2T>G, c.1206delA, c.436+1G>T, c.1217G>T, and g.22,215,887–22,395,767del (179880 bp deletion including exon 16–22 and ZNF645). Six previously reported mutations were found in 11 patients. Among 12 different PHEX mutations, 6 were de novo mutations. Patients with de novo PHEX mutations often had delayed diagnosis and significantly shorter in height than those who had inherited PHEX mutations. Novel compound heterozygous mutations in SLC34A3 were found in one patient and his asymptomatic sister: c.1335+2T>A and c.1639_1652del14. No mutation was detected in two families. Conclusions This is the largest familial study on Turkish patients with hereditary hypophosphatemia. PHEX mutations, including various novel and de novo variants, are the most common genetic defect. More attention should be paid to hypophosphatemia by clinicians since some cases remain undiagnosed both during childhood and adulthood.

Serum galectin-1 levels are positively correlated with body fat and negatively with fasting glucose in obese children

&NA; Galectin‐1, a recently identified peptide, is primarily released from the adipose tissue. Although galectin‐1 was shown to have an anti‐inflammatory effect, its specific function is not clearly understood. We aimed to evaluate the relationship of serum galectin‐1 levels with clinical and laboratory parameters in childhood obesity. A total of 45 obese children (mean age: 12.1 ± 3.1 years) and 35 normal‐weight children (mean age: 11.8 ± 2.2 years) were enrolled. Clinical [body mass index (BMI), waist circumference (WC), percentage of body fat and blood pressure] and biochemical [glucose, insulin, lipids, galectin‐1, high‐sensitive C‐reactive protein (hsCRP) and leptin levels] parameters were assessed. Serum galectin‐1, hsCRP and leptin levels were significantly higher in obese children than those in normal‐weight children (12.4 vs 10.2 ng/mL, p < 0.001; 3.28 vs 0.63 mg/L, p < 0.001; 8.3 vs 1.2 ng/mL, p < 0.001, respectively). In obese children, galectin‐1 levels correlated negatively with fasting glucose (r = −0.346, p = 0.020) and positively with fat mass (r = 0.326, p = 0.026) and WC standard deviation score (SDS) (r = 0.451, p = 0.002). The multivariate regression analysis demonstrated that serum galectin‐1 levels were significantly associated with fasting glucose and WC SDS. This study showed that obese children had significantly higher galectin‐1 levels in proportion to fat mass in obese cases than those in healthy children, which may be interpreted as a compensatory increase in an attempt to improve glucose metabolism. HighlightsThis is the first to display higher galectin‐1 levels in obese subjects than healthy children.The specific role of galectin‐1 in obese subject is not clear.Galectin‐1 is positively correlated with body fat and waist circumference in obese subjects.Galectin‐1 is negatively correlated with fasting glucose.Galectin‐1 may have an effect of improving glucose metabolism in obese subjects.

Brain injury markers: S100 calcium-binding protein B, neuron-specific enolase and glial fibrillary acidic protein in children with diabetic ketoacidosis

To investigate serum levels of brain injury markers in diabetic ketoacidosis (DKA) and the relation of these markers with clinical and radiological findings of brain injury and laboratory results.

A Novel De Novo Missense Mutation in HNF4A Resulting in Sulfonylurea-Responsive Maturity-onset Diabetes of the Young

Maturity-onset diabetes of the young (MODY) is a monogenic subgroup of diabetes mellitus characterized by autosomal dominant inheritance, non-insulin diabetes onset usually before 25 years of age and decreased insulin production or secretion response to glucose. At least 13 different genes have been reported to be associated with MODY to date (1). Approximately 1-2% of patients with diabetes have a monogenic type (2). The inactivating mutations in the nuclear transcription factor 1 homeobox A (HNF1A), the hepatocyte nuclear factor 4 homeobox (HNF4A) and the glucokinase (GCK) are the most common causes of MODY (3). Other genes associated with MODY are infrequently detected: HNF1B, IPF, NEUROD, PDX1, KLF11, CEL, PAX4, BLK, ABCC8 and KCNJ11 (3). While the heterozygous inactivating mutations in the GCK gene lead to asymptomatic mild fasting hyperglycemia, mutations in the genes of HNF1A and HNF4A lead to progressive failure in insulin secretion and worsening of glucose tolerance with age (4). HNF4A is a member of the steroid/thyroid hormone receptor superfamily and plays a major role in glucose stimulated insulin secretion. Homozygous HNF4A mutation is lethal at the early embryonic stage (5). However, ABS TRACT Maturity-onset diabetes of the young (MODY) is a monogenic form of diabetes, with autosomal-dominant inheritance, which usually develops before 25 years of age. MODY is classically caused by a heterozygous mutation of genes known to affect insulin production or secretion. Heterozygous inactivating hepatocyte nuclear factor 4A (HNF4A) mutations, one of the rare subtypes of MODY, cause impaired insulin secretion and subsequent glucose intolerance especially in adolescence. Conversely, HNF4A mutations are also known to be associated with macrosomia and hyperinsulinemic hypoglycemia in newborns. Herein, we report a rare cause of diabetes resulting from a novel heterozygous mutation in the HNF4A gene. In conclusion, genetic testing should be considered in order to establish an accurate diagnosis and provide an opinion in determining the appropriate type of treatment.

Early-Onset Isolated Bilateral Pheochromocytoma As a Major Clinical Manifestation of von-Hippel Lindau Syndrome Type 2C

48 ©Copyright 2018 by Ege University Faculty of Medicine, Department of Pediatrics and Ege Children’s Foundation The Journal of Pediatric Research, published by Galenos Publishing House. Ad dress for Cor res pon den ce Ayhan Abacı MD, Dokuz Eylül University Faculty of Medicine, Department of Pediatrics, Division of Pediatric Endocrinology, İzmir, Turkey Phone: +90 232 412 60 76 E-mail: ayhanabaci@gmail.com ORCID ID: orcid.org/0000-0002-1812-0321 Re cei ved: 23.11.2016 Ac cep ted: 13.12.2016 1Dokuz Eylül University Faculty of Medicine, Department of Pediatrics, Division of Pediatric Endocrinology, İzmir, Turkey 2Ege University Faculty of Medicine, Department of Medical Genetics, İzmir, Turkey 3Dokuz Eylül University Faculty of Medicine, Department of Pediatrics, Division of Pediatric Intensive Care Unit, İzmir, Turkey 4Dokuz Eylül University Faculty of Medicine, Department of Pediatrics, İzmir, Turkey 5Dokuz Eylül University Faculty of Medicine, Department of Pediatric Surgery, İzmir, Turkey Sezer Acar1, Hale Tuhan1, Korcan Demir1, Ayça Aykut2, Asude Durmaz2, Ünal Utku Karaarslan3, Gözde İnci4, Oğuz Ateş5 Ece Böber1, Ayhan Abacı1

Genetic Causes of Rickets

Rickets is a metabolic bone disease that develops as a result of inadequate mineralization of growing bone due to disruption of calcium, phosphorus and/or vitamin D metabolism. Nutritional rickets remains a significant child health problem in developing countries. In addition, several rare genetic causes of rickets have also been described, which can be divided into two groups. The first group consists of genetic disorders of vitamin D biosynthesis and action, such as vitamin D-dependent rickets type 1A (VDDR1A), vitamin D-dependent rickets type 1B (VDDR1B), vitamin D-dependent rickets type 2A (VDDR2A), and vitamin D-dependent rickets type 2B (VDDR2B). The second group involves genetic disorders of excessive renal phosphate loss (hereditary hypophosphatemic rickets) due to impairment in renal tubular phosphate reabsorption as a result of FGF23-related or FGF23-independent causes. In this review, we focus on clinical, laboratory and genetic characteristics of various types of hereditary rickets as well as differential diagnosis and treatment approaches.

Presentation of central precocious puberty in two patients with Tay-Sachs disease

Tay-Sachs disease is an autosomal recessive type of lysosomal storage disorder. The disease is very rare in Turkey, with an incidence of 0.54/100,000. The clinical manifestations of Tay-Sachs disease include progressive developmental delay, seizures, deafness, blindness, spasticity, and dystonia, which are caused by the accumulation of gangliosides in the central nervous system. To date, only one case indicating the association between Tay-Sachs disease and central precocious puberty has been reported. Although the mechanism of this association is not clear, it is thought to be due to ganglioside accumulation in the central nervous system or the inhibition of the hypothalamic inhibiting pathway. Herein, we report two patients with genetically proven Tay-Sachs disease who developed central precocious puberty during follow-up. Pubertal development in patients affected by Tay-Sachs disease should be carefully assessed.

A Rare Cause of a 46,XY Disorders of Sex Development: Persistent Mullerian Duct Syndrome

Persistent müllerian duct syndrome (PMDS) is a relatively rare form of a 46,XY disorders of sex development and clinically characterized by undescended testes and the presence of mullerian duct derivatives such as a uterus and fallopian tubes in males with normal external genitalia. The disease is frequently caused either by the genetic defect of the anti-müllerian hormone (AMH) or its receptor AMH receptor type 2 (AMHR2) gene. AMHR2 mutations have been reported in 45% of genetically proven cases with PMDS. The most common referral findings are bilateral cryptorchidism or transverse testicular ectopia. The presence of uterus and tubes is usually detected during surgery for cryptorchidism. Herein we have presented a PMDS patient with previously reported homozygous AMHR2 mutation, in whom müllerian structures (uterus and fallopian tubes) were detected during laparoscopic intervention performed with the indication of bilateral undescended testis.

A Mutation in INSR in a Child Presenting with Severe Acanthosis Nigricans

Rabson-Mendenhall syndrome (RMS) is an autosomal recessive disorder due to mutations in the insulin receptor gene (INSR) which is mapped to 19p13.2. RMS is characterized by acanthosis nigricans, generalized lanugo, tooth and nail dysplasia, high nasal bridge, and growth retardation. A 5-year-old female patient was referred due to acanthosis nigricans and generalized lanugo. On her physical examination, severe acanthosis nigricans of the neck, axillae, the external genitalia and antecubital regions, generalized lanugo, mildly decreased subcutaneous fat, dysmorphic facial features, and polydactyly on her left hand were noted. Insulin resistance and impaired glucose tolerance were found. Sequence analysis of the INSR in the patient revealed c.3529+5G>A mutation in homozygous state. RMS should be suspected in a patient with characteristic physical features and insulin resistance.