Band 33, Heft 4

Background Obesity and overweight are among the most common and serious health issues in many countries, leading to numerous medical consequences such as heart disease, hypertension, fatty liver etc. This review article addressed the prevalence of obesity and overweight in Iranian students by using meta-analysis. Methods A number of domestic and international databases were searched, including IranMedex, Magiran, SID, Scopus, PubMed, IranDoc, Web of Science and Google Scholar. Eligible publications were 160 articles that addressed the prevalence of obesity or overweight. Data were combined using random effects model. Heterogeneity of the studies was examined by Q statistics and the I 2 index. Data were analyzed using STATA version 11.1. Results In the 160 reviewed studies, a total of 481,070 individuals (6–20 years) were included. The prevalence of obesity among Iranian students based on body mass index (BMI) was 11% (95% confidence interval [CI]: 10%–12%) (in girls 8% [95% CI: 7%–10%] and in boys 11% [95% CI: 10%–13%]). The prevalence of overweight in students based on BMI was 12% (95% CI: 12%–13%) (in girls 13% [95% CI: 11%–14%] and in boys 11% [95% CI: 18%–30%]). The rate of obesity was 13% (95% CI: 11%–16%) in elementary school students, 10% (95% CI: 7%–14%) in secondary school students and 7% (95% CI: 6%–9%) in high school students. Conclusions The prevalence rate of overweight was more than that of obesity with a 1% difference. The prevalence of obesity was higher in boys, while the prevalence of overweight was higher in girls. The prevalence of obesity was higher in primary school students than in secondary school students. This prevalence was higher in secondary school students than in high school students.

Background In the United States, 18.5% of children are obese. Dietary and lifestyle modifications are key, but often ineffective. There are limited approved pediatric pharmacotherapies. The objective of this study was to evaluate current treatment practices for pediatric obesity among members of the Pediatric Endocrine Society (PES, n = 1300) and the Pediatric Obesity Weight Evaluation Registry (POWER, n = 42) consortium. Methods A 10-question online survey on treatment of children with obesity in clinical practice was conducted. Results The response rates were 19% for PES and 20% for POWER members. The majority were female (65%) and board certified in pediatric endocrinology (81%). Most practitioners saw 5–10 patients with obesity/week and 19% prescribed weight-loss medications. POWER participants were more likely to prescribe weight-loss medications than PES participants (46% vs. 18%, p =  0.02). Metformin was the most commonly prescribed medication. Response to medication was poor. Use of dietary non-pharmacological treatment options was uncommon. Over half of the respondents (56%) referred patients for bariatric surgery and 53% had local access to pediatric bariatric surgery. Conclusions Metformin was the most common drug prescribed among respondents, but successful weight-loss responses were uncommon. Among practitioners who are using pharmacological interventions, therapeutic strategies vary widely. Targeted research in pharmacologic and surgical treatment for pediatric obesity is urgently needed.

Background Clinical or biochemical markers that have good correlation with magnetic resonance proton density fat fraction (MR PDFF) can be used as simple tools for the screening for nonalcoholic fatty liver disease (NAFLD) and in determining the degree of fatty infiltration of the liver. The objective of this study was to determine the degree of relationship between MR PDFF and ultrasonography (USG) grades of fatty liver, and clinical and biochemical parameters of adolescents and to determine the sensitivity and specificity of USG for diagnosis of NAFLD. Methods This prospective study included 34 overweight adolescents (mean age, 12.1 ± 1.5 years; range, 10–15.1 years; 10 girls and 24 boys) who underwent both USG and magnetic resonance imaging (MRI). Correlation analysis was performed between MR fat fraction and USG grades of fatty liver, and clinical and biochemical parameters of fatty liver disease. Results MR fat fraction had a moderate positive correlation with serum alanine transaminase (ALT) and aspartate transaminase (AST) (ρ = 0.634, p < 0.001, ρ = 0.516, p = 0.002, respectively) and had a negligible or weak correlation with body mass index (BMI), BMI standard deviation score (SDS), waist circumference (WC), fasting insulin, homeostatic model assessment of insulin resistance (HOMA-IR), serum triglyceride, low-density lipoprotein (LDL), high-density lipoprotein (HDL) and total cholesterol levels. The sensitivity and specificity of USG in the diagnosis of NAFLD were 81% (95% confidence interval 54%–95%) and 50% (27%–73%), respectively. The MR fat fraction had a moderate positive correlation with ultrasound grades of fatty liver (ρ = 0.487, p = 0.003). Conclusions Serum ALT and AST are potential biochemical markers to assess the degree of hepatic steatosis in NAFLD, which needs validation in further studies. USG can be used as a screening tool for NAFLD, but the diagnosis should be confirmed by estimating the MR fat fraction.

Background Obesity in children and adolescents has increased alarmingly, placing them at a higher risk for impaired glucose tolerance and type 2 diabetes. The prevalence of vitamin D deficiency has increased as well. Vitamin D is critical for glucose homeostasis and insulin secretion. Studies on adults have reported an inverse association between vitamin D levels and insulin resistance (IR), but the results in children are inconsistent. The aim of our study was to determine the association between IR and serum vitamin D levels in obese Mexican children and adolescents. Methods A cross-sectional study was performed on 227 children and adolescents between 6 and 19 years of age. Obesity was diagnosed through body mass index (BMI) for age, according to the World Health Organization (WHO) criteria (2007). 25-Hydroxyvitamin D (25[OH]D) was measured using an immunoassay technique and the homeostatic model assessment of insulin resistance (HOMA-IR) was calculated using the Matthews equation. Student’s t-test was carried out. Results The mean serum 25(OH)D level was 35.80 ng/mL, and 55.1% of the subjects had levels classified as sufficient, 33.5% as insufficient, and 11.5% as deficient. The mean level of HOMA-IR was 3.16, and 70% of the subjects were diagnosed with IR. Fasting insulin levels and HOMA-IR were significantly different in adolescents with hypovitaminosis, compared with adolescents in the vitamin D sufficiency group (p = 0.01 and p = 0.03, respectively). Conclusions The insulin levels and HOMA-IR were higher in adolescents with hypovitaminosis. The girls presented higher levels of insulin and HOMA-IR than the boys.

Background Elevated serum uric acid concentrations have been associated with metabolic syndrome. However, only limited information is available on the prevalence of hyperuricaemia in adolescents. Therefore, the aim of our cross-sectional study was to study the prevalence of hyperuricaemia and dietary patterns in adolescents aged 13–16 years living in Yangzhou, China. Methods Adolescents were asked to complete a 20-item food frequency questionnaire (FFQ) and provide an overnight fasting finger-prick sample. Principal component analysis (PCA) with varimax rotation was used to derive the dietary patterns that might be associated with high uric acid concentrations. Results A total of 1070 adolescents were recruited. Of these, 53.6% (n = 574) were females, and 58.5% (n = 625) were within the normal body mass index (BMI) range. The males had a significantly higher serving size and frequency in their weekly food consumption, including meat, poultry, Chinese cereal staple foods and Western-style fast foods, than the females (all p < 0.02). The overall mean serum uric acid concentration and prevalence of hyperuricaemia were 368.6 ± 114.5 μmol/L and 37.9%, respectively. The prevalence of hyperuricaemia was 4.633 times greater among the participants who were overweight and obese than among those who were underweight. On the other hand, the prevalence of hyperuricaemia was 0.694 times lower among the participants who had normal weight than those who were underweight. Conclusions The prevalence of hyperuricaemia was relatively high in Chinese adolescents. The prevention of hyperuricaemia measures should be strengthened in adolescents to effectively control for obesity and gout, which tend to persist into adulthood.

Background Dietary patterns have a crucial role in modulating chronic inflammation. This study aimed to determine the relationship between the Dietary Inflammatory Index (DII) and inflammation markers and metabolic syndrome components in adolescents (n = 343). Methods Fasting glucose, fasting insulin and lipid profile were analyzed and blood pressures were measured. Analysis of inflammation markers such as sedimentation, leukocyte, C-reactive protein (CRP), tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6) was also performed. The DII scores were calculated based on the adolescent’s 3-day food consumption records. Results The dietary inflammatory score varied between 1.04 and 5.11 (3.6 ± 0.82). There was no significant difference in leukocyte and CRP levels between quartiles (p > 0.05). Those in the fourth quartile were observed to have higher levels of TNF-α and IL-6 compared to the others (p < 0.05). In the multiple regression analysis, a positive correlation existed only between IL-6 and DII, independent of other inflammatory markers (β = 0.272; p < 0.05). The DII was associated with glucose intolerance (odds ratio [OR] for DII quartile 4 compared to 1 = 3.5, 95% confidence interval [CI] = 1.2–10.4) and dyslipidemia (OR for DII quartile 4 compared to 1 = 5.3, 95% CI = 1.7–16.8). Conclusions These data suggest that a higher DII score was significantly associated with an increased risk of metabolic syndrome and some metabolic syndrome components in adolescents. Hence, DII can be used to determine the inflammatory potential of a diet and a healthy diet with anti-inflammatory properties that may be conducive to the prevention of metabolic disorders.

Background The appendix testis (AT) is the most common vestigial remnant of the human testis. Variations in the presence and expression of AT androgen receptor (AR) and estrogen receptor (ER) have been reported in cryptorchidism. We studied the possible association of AR and ER expression of the AT with cryptorchidism. Methods ATs were resected from 40 boys who underwent inguinoscrotal surgery, (20 patients with congenital unilateral cryptorchidism [UC] and 20 controls with orthotopic testes and hydrocele). AR and ER expression was evaluated with immunohistochemistry, and the percentage and intensity of AR and ER expression were evaluated by the Allred scoring method. AT length was compared between the two groups. Correlation of AR and ER expression was evaluated independently in patients and controls. Results The Allred score for AR trended toward lower values in UC compared to controls (p = 0.193), while ER scores presented statistically significant lower values in UC compared to controls (p = 0.017). No significant difference or trend was found in the expression of both receptors between high and low cryptorchidism (p = 0.981 for AR, p = 0.824 for ER) and for the appendiceal length between UC and controls (p = 0.369). Conclusions The findings of a trend for lower AR expression and a statistically significant lower expression of ER in UC may suggest an association of AR and ER with cryptorchidism and may provide an insight into the process of testicular descent.

Background Autoimmune thyroid diseases (ATDs) can be classified into two basic diseases: Graves’ disease (GD) and Hashimoto’s thyroiditis (HT). Here, we review the effectiveness of laboratory and imaging methods used for the early diagnosis of ATD and draw attention to methods that may improve screening. Methods Retrospective data of 142 patients diagnosed with ATD between January 2010 and December 2015 at our paediatric endocrinology clinic were used. Sociodemographic characteristics, clinical findings, treatments and follow-up data of patients were statistically evaluated. Results Of the ATD cases, 81% (n = 115) were female. The median age was 12.5 ± 3.5 (range 1–17) years and 91% (n = 129) of patients were in puberty. There was a significant positive correlation between the height (standard deviation score) and follow-up time for patients with HT (r = 0.156, p < 0.01). Thyroglobulin antibody (TgAb) positivity was found in 75% (45/60) of females with a positive maternal ATD history (p = 0.045). Thyroid-stimulating hormone (TSH), free triiodothyronine (fT3), free thyroxine (fT4) values were significantly altered during the treatment follow-up period in female patients with GD and HT, while only fT4 values were found to be significantly altered in boys with HT. Conclusion Although GD and HT have similar mechanisms, they differ in terms of treatment duration and remission and relapse frequencies. Ultrasonography (USG) screening is a non-invasive procedure that is suitable for all patients with ATD. Based on our results, TgAb could be useful in the screening of girls with a history of maternal ATD.

Background Gestational weight gain (GWG) influences both fetal and maternal health. Leptin is a biomarker that may predict the early development of obesity and greater weight gain in childhood. Newborns with higher neonatal weight have been found to have higher leptin levels in umbilical cord blood (UCB). There are few studies that evaluate leptin levels in UCB according to GWG in women with a normal body mass index (BMI). The aim of the present study was to determine whether the levels of leptin in UCB in neonates born to mothers with a high GWG were higher, compared with levels in newborns whose mothers had a low GWG. Methods A cross-sectional analytic study was conducted on 65 primigravidas. They were under 30 years of age, had normal pregestational BMIs, no associated diseases and were classified as having high (n = 22) or low (n = 43) GWG. The neonatal UCB leptin levels were measured and both neonatal and maternal anthropometric evaluations were carried out. The quantitative variables were compared through the Mann-Whitney U test and Student’s t test, as appropriate. Results UCB leptin levels were higher in the neonates whose mothers were in the high GWG group, compared with those born to mothers in the low GWG group (7.0 [1.9–11.4] vs. 2.9 [1.2–6.7] ng/mL, p = 0.020). When stratified by sex, that difference was maintained only in male neonates. Conclusions UCB leptin levels were higher in neonates born to mothers with a high GWG, compared with those in newborns whose mothers had a low GWG.

Background To determine the prevalence of serum zinc deficiency and provide the age- and sex-specific percentile values of serum zinc in children and adolescents. Methods We used the gathered data through the CASPIAN-V study, a national survey conducted on 3500 students aged 7–18 years from 30 provinces of Iran. In this study, 1370 blood samples were selected randomly, and serum zinc concentration was measured using a Hitachi automated analyzer. Zinc deficiency was defined as a serum zinc level of less than 75 μg/dL. Age-sex specific reference percentile values were developed for serum zinc concentration. Results The mean age of participants was 12.4 ± 3.0 years; 49.3% were girls and 73% were urban inhabitants. Mean (standard deviation [SD]) of serum zinc concentration was 107.23 (25.81) μg/dL with a significant sex difference; 109.03 ± 26.12 μg/dL for males compared to 105.41 ± 25.3 μg/dL for females (p = 0.009). The prevalence of subclinical zinc deficiency was 4.9% (95% confidence intervals [CI]: 3.0, 6.9) in children and adolescents. Both zinc deficient and sufficient groups were similar in terms of age, sex and residential areas (all p-value > 0.05). Overall, the 5th and 95th percentile values for serum zinc were 68.28 and 151.87 μg/dL, respectively. The value of all percentiles consistently decreased with age. The 10–99th percentile values for serum zinc were greater in boys than girls at all ages. Conclusions Nearly 5% of subjects had zinc deficiency. Age-sex specific percentile values were established for Iranian children and adolescents.

Background To assess the efficacy and safety of lipid-lowering treatment in children with heterozygous familial hypercholesterolemia (HeFH) aged ≤12 years attending a tertiary hospital-based outpatient lipid clinic. Methods Data in 318 children from the University Hospital of Ioannina (Northwestern Greece) Outpatient Lipid Clinic Project for Children and Adolescents with Dyslipidemia from March 2009 to December 2018 were analyzed. We assessed the efficacy and safety treatment alongside any possible predictors of the achievement of the treatment target. Results Of 318 children with hyperlipidemia, 72 were diagnosed having HeFH based on clinical criteria and genetic confirmation. Compared with non-familial hypercholesterolemia (non-FH) children, those with FH had a higher occurrence of positive family history of premature cardiovascular disease, and higher levels of total, low-density lipoprotein-cholesterol (LDL-C), apolipoprotein B (apoB) and lipoprotein (a) (Lp(a)). Treatment regimens included either atorvastatin 10–20 mg/day, rosuvastatin 5–10 mg/day, pitavastatin 2–4 mg/day monotherapy or in combination with ezetimibe. The treatment goal of LDL-C (<135 mg/dL, 3.5 mmol/L) was achieved in 69% of children treated. The achievement of the treatment targets correlated positively with male sex and inversely with the Dutch Lipid Clinic Network Score, baseline total, LDL-C and apoB levels. No clinically significant changes in liver or muscle-related laboratory tests were reported; no effect on growth or sexual maturation was noted. Conclusions This study confirms that lipid-lowering treatment in HeFH children initiated in the setting of a specialized tertiary hospital-based outpatient lipid clinic is efficacious and safe. Children of male sex and low baseline lipid values had a better achievement of treatment target.

Background Down syndrome (DS) is a common chromosomal disease resulting in neurodegeneration. Cognitive competence has been assessed among adults with DS using various methods because DS patients have a tendency to develop Alzheimer’s disease (AD) after middle age. However, research describing cognitive assessments in DS children is not as many as in DS adults, let alone with regard to performed analyses to determine factors that predict cognitive assessments. In this study, we evaluated the Gesell Developmental Schedules (GDS) scores and their associations with the relevant biochemical indicators and demographic factors in DS children. Methods All the subjects underwent GDS testing. The plasma amyloid-β (Aβ) peptide and serum vitamin A (VA) values were measured with enzyme-linked immunosorbent assay and high-performance liquid chromatography, and in the meanwhile, the demographic information of the subjects was collected. Results Forty-six DS children were recruited for this study. The GDS scores of children with DS were lower than those in children without DS. The plasma Aβ40 and Aβ42 levels were negatively associated with the GDS scores. Moreover, the GDS scores of the non-VA deficiency (NVAD) group were significantly higher than those of the VA deficiency (VAD) group. Certain demographic characteristics, such as the paternal labor intensity and paternal educational status, were relevant factors with regard to the GDS scores of the DS children. Conclusions This study determined that DS children exhibited abnormal GDS scores which indicated developmental delay of children with DS; the levels of plasma Aβ40, Aβ42 and serum VA were influential biochemical indicators and the paternal labor intensity and educational status were related demographic factors.

Background Pompe disease (PD) is an autosomal recessive metabolic myopathy with an average incidence of one in 40,000 live births. It has a variable age of onset and can be diagnosed within the first 3 months. Heart involvement and muscle weakness are its primary manifestations. Case presentation We describe two families affected by PD with two rare, novel variants. To date, pathogenic variants in acid α-glucosidase ( GAA ) alone have accounted for all cases of the disease. Both families were screened for pathogenic sequence variations. This study presents the implications of regulatory or modifier sequences in the disease pathogenesis for the first time. A homozygous missense p.Arg854Gln variant in family A and a single heterozygous variant (p.Asn925His) in family B were found to be segregating according to the disease phenotype. The variants were not detected in our in-house database comprising 50 whole-exome sequences of healthy individuals from a local unrelated Pakistani population. In silico analyses predicted that the variants would have deleterious effects on the protein structure. Conclusions The variants likely underlie the infantile-onset PD (IOPD) in these Pakistani families. The study expands the mutation spectrum of GAA associated with IOPD and highlights the insufficiency of screening the GAA coding sequence to determine the cause of IOPD. The work should be helpful in carrier identification, improving genetic counselling, and prenatal diagnosis.

Background Hereditary vitamin D-resistant rickets (HVDRR) is caused by vitamin D receptor (VDR) defects. Patients with HVDRR do not respond to standard doses of calcitriol and oral calcium (Ca) treatment and need to be treated with intravenous Ca (IV-Ca) via a central route. However, central catheter-related complications can cause significant morbidity. Case presentation Four unrelated patients with HVDRR presenting with rickets and alopecia totalis were administered intermittent IV-Ca treatment (2–5 times/week) through a peripheral route. No complications such as infection, extravasation or arrhythmias were detected upon peripheral infusion. Peripheral 1–22 months’ duration of IV-Ca normalized parathyroid hormone (PTH) and alkaline phosphatase (ALP) in all patients, after which, oral Ca of 200–400 mg/kg/day and calcitriol of 0.5 μg/kg/day were sufficient to maintain normal PTH levels. Molecular studies on the VDR gene showed a previously reported homozygous c.454C > T (p. Q152* ) pathogenic variant in two patients. Two novel homozygous variants in the other two patients were detected: (1) c.756-2A > G , which affects the splice acceptor site, and (2) c.66dupG (p.I23Dfs*20) variant leading to a frameshift that results in a premature stop codon. Conclusions Peripheral IV-Ca treatment is an effective and practical alternative treatment mode that provides dramatic clinical benefit in patients with HVDRR.

Background Alterations in the structure and activity of 4-hydroxyphenylpyruvate dioxygenase (HPD) are causally related to two different metabolic disorders: recessively inherited tyrosinemia type III and dominantly inherited hawkinsinuria. The aim of this study was to provide a new perspective for the clinical understanding of the pathogenesis of tyrosinemia type III or hawkinsinuria. Case presentation A full-term newborn baby born after a safe pregnancy and childbirth with a birth weight of 3200 g and another full-term baby born after a safe pregnancy and childbirth with a birth weight of 2800 g are reported and analysed. DNA extraction, next-generation sequencing, bioinformatics analysis, Sanger sequencing and biochemical analysis were performed. One patient with a heterozygous HPD gene (NM_002150.2) c.460G > A mutation and one patient with a heterozygous HPD gene (NM_002150.2) c.248delG mutation showing elevated tyrosine levels upon newborn screening by tandem mass spectrometry (MS/MS) are reported. Conclusions The HPD gene may not be a strictly autosomal recessive pathogenic gene, which provides a new perspective for the clinical understanding of the pathogenesis of tyrosinemia type III or hawkinsinuria.

Pyruvate carboxylase (PC) deficiency is a rare autosomal recessive disease and provides clinics in three essential phenotypes. Type B PC deficiency is characterized by lactic acidosis and hyperammonemia. We report a Turkish patient who was diagnosed with type B PC deficiency. Despite the application of anaplerotic treatment with biotin, citrate and arginine-aspartate, continuous veno-venous hemodialysis (CVVHD) treatments were applied due to the failure to keep hyperammonemia and lactic acidosis under control. Ammonia values increasing to 860 μmol/L were observed. A homozygous novel variant was detected in PC gene analyses containing a 12-base pair deletion on exon 8. Although the mutation found was not reported previously, it was accepted as a pathogenic variant due to its presence in a functional region of the protein. In type B PC deficiency, although a high level of ammonia is expected, it rarely exceeds 200 μmol/L. As far as we know, the present case has the highest ammonia values in the literature. This paper has been shared to highlight to keep PC deficiency in mind regarding the differential diagnosis of hyperammonemia, particularly in the presence of lactic acidosis, and to serve as a model for the use of different modalities in the management process of PC deficiency.

Background Autoimmune polyglandular syndrome type II (APS II) is defined as the combination of autoimmune adrenal insufficiency and autoimmune thyroid disease (AITD) and/or type I diabetes mellitus (T1DM) in the same patient. Case presentation A 15-year-old boy had a history of weight loss, nausea and vomiting, headache, restlessness, and tanned skin. He was diagnosed with Graves’ disease. Two weeks after carbimazol therapy was commenced, he presented with adrenal crises (fever, arterial hypotension, hyponatremia, adrenocorticotropic hormone [ACTH] 1119.6 ng/mL [normal range <60] and low cortisol). He received hydrocortisone and fludrocortisone, and improved quickly. Thyroid-stimulating hormone (TSH) receptor autoantibodies as well as 21-hydroxylase antibodies were elevated. Conclusions Although the combination of Graves’ and Addison’s disease is extremely rare, especially in children, it is critical to make the diagnosis. Accelerated metabolic rate increased the risk for adrenal crises in our patient. This case contributes to the spectrum of APS II and its manifestation.