Metabolic syndrome in children and adolescents: Old concepts in a young population

Many years after first being described, there is still no clear consensus on diagnostic criteria for metabolic syndrome, particularly in children. However, identification of this cluster of cardiovascular risk factors especially in children with co‐morbidities, is important in order to reduce their future risk of chronic disease and morbidity. Sustained multidisciplinary and family‐based early intervention is required, aiming primarily at life‐style change.     

The effect of deferasirox on endocrine complications in children with thalassemia

Abstract

Endocrine system dysfunctions are the significant complications of excessive iron overload in beta thalassemia patients. The aim of this study was to evaluate the long-term effect of chelation with deferasirox on endocrine complications. The study group consisted of children with beta thalassemia who had been evaluated for the growth and pubertal development, bone metabolism, thyroid/parathyroid functions, glucose metabolism dysfunctions in the department of pediatric hematology of Ankara D??kap? Child Health and Diseases Hematology Oncology Training And Research Hospital between 2009-2011 and reevaluated after deferasirox chelation therapy in 2018. Thirty-one transfusion dependent beta-thalassemia patients were enrolled for the study. Seventeen (54.8%) patients were male and the mean age was 16.9?±?3.8 (9-23) years. Splenectomy was performed in 11 patients (35.5%). In the initial evaluation, 26 patients (84%) received deferoxamine and/or deferiprone and five (17%) patients received deferasirox as a chelator; in the final evaluation all patients were receiving deferasirox. The mean duration of deferasirox treatment was 5.9?±?2.02?years (1-10?years). Of the 26 patients who had endocrine complications between 2009-2011, 18 were recovered. In the final evaluation, eight patients (25%) developed new endocrinopathies. The frequency of endocrine complications seen before the deferasirox treatment (83%) was higher than the frequency of complications while receiving deferasirox treatment (25.8%) (p?<?0,05). In this study, it was determined that both existing endocrine abnormalities were reduced and recent developed problems were less likely with long-term deferasirox treatment in thalassemia patients.     

Role of vagotony in sinus node dysfunction in children with symptomatic congenital long QT syndrome

The present study examined chronotropic dysfunction and the role of vagotony in congenital long QT syndrome, sinus node function and the effects of parasympathetic blockade. Six patients with congenital long QT syndrome were studied. The four males and two females, aged 1–15 years, had episodes of syncope and malignant ventricular arrhythmias. Congenital long QT syndrome was defined as a corrected QT interval greater than 0.45 s, T wave alternans and the age at diagnosis. The sinus heart rate measured from a 24 h electrocardiograph was abnormally low (< 50 min) in three patients (1, 4 and 5 years old) and did not increase sufficiently with the administration of atropine in five of the six patients with congenital long QT syndrome. From intracardiac electrophysiological studies, the corrected sinus node recovery time was prolonged in three patients and the total sinoatrial conduction time was prolonged in two patients. In most patients who had an abnormally long sinoatrial conduction time and corrected sinus node recovery time, these values returned to normal following atropine administration. In one patient, the corrected sinus node recovery time was prolonged paradoxically by atropine. Sinus node dysfunction in congenital long QT syndrome was affected by vagotony associated with a right sympathetic nerve system abnormality.     

Metabolic syndrome in youths

Abstract:  The metabolic syndrome (MetS), characterized by a clustering of cardiovascular disease and type 2 diabetes (T2DM) risk factors, has become prevalent in children and adolescents in recent years. However, the reported prevalence data on the MetS in youths has varied markedly, in large part, because of the disagreement among the variously proposed definitions of the MetS. Obesity is defined by using body mass index, waist circumference, or percent overweight, pointing to the need for standardized use of anthropometric variables to define obesity with a well-defined reference year for each ethnic population. In addition, slightly different cutoff values are used for triglycerides, high-density lipoprotein cholesterol, blood pressure, and fasting plasma glucose. Therefore, International Diabetes Federation recently proposed unified, easy-to-use criteria for diagnosing the MetS in youths. To provide insight into the mechanisms underlying the MetS in youths, the degree of insulin sensitivity/resistance and its correlation with the serum lipid and blood pressure levels have been evaluated. In addition, the serum levels of adipocytokines, such as adiponectin, leptin, tumor necrosis factor-α, resistin, interleukin-6, plasminogen activator inhibitor-1, and their correlation with childhood obesity have been extensively investigated. Recommendations for future research include exploring ways to assess visceral adiposity, to identify better biochemical markers for prediction of T2DM and disease progression, and to effectively intervene to prevent the MetS in youths.     

Permanent consequences in Langerhans cell histiocytosis patients: a pilot study from the Histiocyte Society-Late Effects Study Group

BACKGROUND: Permanent consequences (PC) are often described among subjects with Langerhans cell histiocytosis (LCH) but data on the real incidence are scarce. Within the Histiocyte Society (HS), and in order to design a definitive late effects study, a retrospective survey was organized to describe the prevalence of PC among long-term survivors of LCH. METHODS: Nine institutions contributed with their LCH patients having a minimum follow-up of 3 years. Information was collected on their disease-history, and on type and date of onset of any PC. Because of the retrospective type of this study, it was accepted that each institution might have used different criteria to assess PC. RESULTS: One hundred eighty-two subjects were registered and in 95 (52%) at least 1 PC was reported. For some specific PC (e.g., anterior pituitary dysfunction) information was too scarce to provide reliable data. PC were more frequent among subjects with multisystem (MS) disease (71%), compared to those with single system (SS) disease (24%); P < 0.0001. The most frequently reported PC were diabetes insipidus (DI) (24%) orthopedic abnormalities (20%), hearing loss (13%), and neurological consequences (11.0%). Analysis of cumulative risk showed that some types of PC may become manifest more than 10 years from diagnosis. CONCLUSIONS: This survey on selected cases of LCH survivors has confirmed that late sequels are frequent, and that they are even more common among those with MS LCH. Our findings highlight the need for long-term and patient-oriented follow-up in children with LCH.     

儿童青少年代谢综合征与ghrelin基因Leu72Met位点多态性研究

目的探讨儿童青少年代谢综合征（MS）及其组分与胰岛素抵抗（IR）的关系,研究ghrelin基因Leu72Met位点多态性在儿童青少年肥胖症及MS中的作用。方法通过对住院的508例中、重度肥胖青少年的临床研究,计算稳态模型胰岛素抵抗指数（HOMA—IR）及总体胰岛素敏感指数（WBISI）评估IR情况;对其中230例肥胖患儿和100名正常体重儿童青少年,利用PCR、RFLP及基因测序检测ghrelin基因多态性。结果中、重度肥胖儿童青少年MS的发生率为22．83％;HOMA-IR和WBISI两个指标在肥胖组与对照组中差异有统计学意义（P〈0．01）,且分别随肥胖程度的增加而升高和下降;与单纯肥胖组比较,伴有代谢组分异常者的HOMA—IR明显增高（P〈0．05）,而WBISI显著降低（P〈0．05）,且随着代谢组分异常的增多而加重。在儿童青少年中检测到两个ghrelin基因的多态性位点,C214A（Leu72Met）和A269T（Gln90Leu）;肥胖组Leu72Met位点的多态性频率为36．09％,与对照组的41．00％比较差异无统计学意义（P〉0．05）;Gln90Leu在肥胖组和对照组的多态性频率分别为043％和2．00％,差异亦无统计学意义（P〉0．05）;Leu72Met位点各基因型之间比较,年龄、体质指数（BMI）、谷丙转氨酶（ALT）、甘油三酯（TG）、总胆固醇（TC）、WBISI差异均无统计学意义。结论肥胖儿童青少年存在IR,且随肥胖程度及MS各代谢组分异常增加而加重;Leu72Met位点的多态性改变与汉族儿童青少年肥胖及MS的发生无关。     

Overweight and obesity in pediatric liver transplant recipients: prevalence and predictors before and after transplant, United Network for Organ Sharing Data, 1987-2010

Perito ER, Glidden D, Roberts JP, Rosenthal P. Overweight and obesity in pediatric liver transplant recipients: Prevalence and predictors before and after transplant, United Network for Organ Sharing Data, 1987–2010.
Pediatr Transplantation 2012: 16: 41–49. © 2011 John Wiley & Sons A/S. Abstract: Obesity is extremely common in adult liver transplant recipients and healthy U.S. children. Little is known about the prevalence or risk factors for post‐transplant obesity in pediatric liver transplant recipients. UNOS data on all U.S. liver transplants 1987–2010 in children 6 months–20 yr at transplant were analyzed. Subjects were categorized as underweight, normal weight, overweight, or obese by CDC guidelines. Predictors of weight status at and after transplant were identified using multivariate logistic regression. Of 3043 children 6–24 months at transplant, 14% were overweight. Of 4658 subjects 2–20 yr at transplant, 16% were overweight and 13% obese. Children overweight/obese at transplant were more likely to be overweight/obese at one, two, and five yr after transplant in all age groups after adjusting for age, ethnicity, primary diagnosis, year of transplant, and transplant type. Weight status at transplant was not associated with overweight/obesity by 10 yr after transplant. The prevalence of post‐transplant obesity remained high in long‐term follow‐up, from 20% to 50% depending on age and weight status at transplant. Weight status at transplant is the strongest predictor of post‐transplant overweight/obesity. To optimize long‐term outcomes in pediatric liver transplant recipients, monitoring for obesity and its comorbidities is important.     

Metabolic syndrome in fifth grade children with acanthosis nigricans: results from the CARDIAC project

Background  A number of cardiovascular disease (CVD) risk factors have been linked to obesity and associated negative health outcomes in children. However, no consistent definition of metabolic syndrome exists for children. In addition, research is needed to systematically examine the prevalence of metabolic syndrome in high-risk children, including those with insulin resistance. This study explores several definitions of metabolic syndrome and determines the prevalence of metabolic syndrome in a large sample of children with acanthosis nigricans (AN). Methods  The study used results from a large-scale screening of fifth-grade students in West Virginia to explore the prevalence of metabolic syndrome among 676 male and female participants who had mild to severe AN. Results  In this high-risk sample of students who had AN, 49% met the criteria, i.e., three risk factors including insulin resistance, high body-mass index, and elevated blood pressure or dyslipidemia, when tested for metabolic syndrome. Children with AN who were classified as obese or morbidly obese were at significantly increased odds of having metabolic syndrome. Conclusions  Results are discussed in terms of systematically defining metabolic syndrome for high-risk children, as well as public health and clinical interventions targeting children who are overweight or obese. The presence of AN and morbid obesity might be easily observed markers for metabolic syndrome.     

Growth failure, encephalopathy, and endocrine dysfunctions in two siblings, one with 5-oxoprolinase deficiency

Two female siblings, born to consanguineous parents, presented with a similar phenotype characterized by severe growth and developmental failure, dysmorphic features, thyroïd and gonadal dysfunction, autistic traits and hand stereotypes resembling Rett syndrome. In the elder patient, analysis of urinary organic acids disclosed a very high excretion of 5-oxoproline (4.2 to 8.1 mol/mol creatinine) and enzyme assays of leucocyte extracts revealed a profound deficiency of 5-oxoprolinase. However, normal urinary organic acid profiles were found in the younger child. In view of their distinct dysmorphic features and severe growth deficiency, these siblings cannot be considered as Rett Syndrome variants. The Dubowitz and carbohydrate-deficient glycoprotein syndromes were also excluded clinically and biochemically respectively. We conclude that these patients suffer from a hitherto undescribed autosomal recessive disorder, unrelated to the 5-oxoprolinase deficiency of the elder sib. Conclusion The present findings give evidence that 5-oxoprolinase deficiency is not associated with a distinct morbid phenotype.     

Metabolic syndrome and leptin concentrations in obese children

Objective Obesity and its complications including metabolic syndrome has been increased in children and adolescents recently. Leptin is known to play an important role in the pathogenesis of obesity. Methods The objective of this study was to evaluate the relationship of leptin and metabolic syndrome in obese Iranian children. A cross sectional study was carried out in 65 primary schools in Tehran. The children with waist circumferences equal or above 90^th percentile for their height and age were chosen for further evaluations. 505 children aged 7–12 years participated in the study. Anthropometric variables measurements, blood pressure, fasting plasma glucose, triglyceride, high-density lipoprotein cholesterol and serum leptin were obtained from the study sample. Results Serum leptin levels were significantly higher in girls in comparison to the boys (with median 11.0 Vs 8.25 ng/dl; P value =0.007). Serum level of leptin were higher in children with metabolic syndrome (median 11.3 Vs 8.9 ng/dl; P value=0.045). However, after adjustment for sex, this association was removed. Conclusion Leptin did not appear to have a major role in metabolic syndrome, even though it was strongly associated with obesity parameters. More studies evaluating the relationship between leptin and metabolic syndrome in various ethnic groups are recommended.     

Intrathecal chemoprophylaxis after HSCT in children

At present, the literature on the efficacy and risks of i.t. chemotherapy to children after HSCT is scarce. Current practices to reduce the risk of leukemic relapse in the CNS after HSCT differ between centers of transplantation. We compared 74 patients (56 ALL/18 AML), who received i.t. therapy post-HSCT with 46 patients (36 ALL/10 AML) who did not receive post-HSCT i.t. therapy. The patients were transplanted at the University Children's Hospital, Uppsala or the Karolinska University Hospital, Huddinge, two Swedish transplantation units with different routines concerning i.t. therapy after HSCT. The primary end-point was the number of isolated CNS relapses. Secondary end-points were other types of relapse, death, and neurological complications. There was no statistically significant difference in the incidence of CNS relapses between the groups (p > 0.05). I.t. therapy did not reduce the overall incidence of isolated CNS relapse or mortality. Our study did not demonstrate a protective effect of i.t. therapy indicating that post-HSCT i.t. therapy may only be of limited use in the treatment of acute childhood leukemia. We conclude that with the risks present, i.t. therapy should be carefully evaluated, and only considered in high-risk cases.     

Bartter's syndrome in Arabic children: review of 13 cases

BACKGROUND: Bartter's syndrome (BS) is an inherited disease of renal potassium wasting characterized by hypokalemic alkalosis, normal blood pressure, vascular insensitivity to pressor agents and elevated plasma concentrations of renin and aldosterone. It is caused by generalized hyperplasia of the juxtaglomerular apparatus at the site of renin production caused by mutations in the Na-K-2Cl cotransporter gene, NKCC2. The objective of our study is to establish the prevalence and incidence of BS in Kuwait and to assess treatment modalities for it. METHODS AND RESULTS: Bartter's syndrome was diagnosed in 13 Kuwaiti children over a 14 year period (1981-1995) with the estimated incidence of 1.7/100,000 live births. The mean age at diagnosis was 9.3 months (range 2-32 months). There were five males and eight females (ratio 1:1.6). The mean duration of follow up was 5.6 years (1-14 years). Both consanguinity and familial history among our patients were high (69 and 54%, respectively). All patients had hypokalemia, hypochloremia with metabolic alkalosis, hyperreninemia and were normotensive. Clinical presentation was essentially similar to that in other series. Eleven patients (85%) had growth failure, two had nephrocalcinosis (15%) and one had renal failure. All patients were treated with supplemental potassium, an aldosterone antagonist (spironolactone) and a prostaglandin synthetase inhibitor (indomethacin or aspirin) sequentially. Significant catch-up of growth (four patients) and increases in serum potassium (eight patients) were recorded after administration of indomethacin therapy. One patient died of severe pneumonia with respiratory failure from hypokalemic myopathy. Clinical presentation, inheritance, complications and therapy of BS are briefly discussed. CONCLUSION: Bartter's syndrome is a rare disease, but should be considered in the differential diagnosis of other disorders with growth failure and/or hypokalemia. Early diagnosis, close follow up and compliance with treatment may lead to appropriate growth and development.     

Metabolic syndrome: signs and symptoms running together

Brady TM, Parekh RS. Metabolic syndrome: signs and symptoms running together.
Pediatr Transplantation 2010: 14: 6–9. © 2010 John Wiley & Sons A/S.
Abstract:  Children with kidney disease are at increased risk of having several comorbidities such as obesity, dyslipidemia, hypertension, and impaired glucose tolerance, and patients with a constellation of these symptoms are considered to have the MS. Children with kidney disease, and ESRD in particular, are at increased CV risk, as are patients with the MS. To determine the impact MS has on a particularly vulnerable population of children, those who have received a kidney transplant, Wilson et al. explored the prevalence of MS and the association of MS with cardiac abnormalities among this subset of children. They found an overall high prevalence of MS among pediatric transplant recipients and that the risk of left ventricular hypertrophy was higher among children with MS after renal transplant compared to those without MS. Review of the most common definitions of MS and also the clinical implications are discussed. While there is no doubt that children with kidney disease have a high prevalence of CV risk factors and that these children are at risk for CV events early in life, whether the sum of the parts of MS confers increased risk over what is seen with individual risk factors that often run together remains to be seen.     

Coexistence of congenital long QT syndrome and autonomic dysregulation in children

Loss of consciousness (LOC) in long QT syndrome (LQTS) patients can be caused by torsade de pointes (TdP) or vasovagal syncope (VVS). On genetic testing and head‐up tilt testing (HUTT), we diagnosed three young patients with both genotyped LQTS and autonomic dysregulation. According to grade of prolongation of QT interval and LOC status, syncope episodes in two patients were classified as due to VVS, while those of the other patient were due to TdP. We also diagnosed one patient with postural orthostatic tachycardia syndrome. Syncope in LQTS patients should not automatically be labeled TdP. If there is a possibility of VVS, HUTT should be performed, but careful observation is required because TdP cannot be completely ruled out.     

出生体质量与儿童代谢综合征的相关性

代谢综合征(metabolic syndrome,MetS)是中心性肥胖、糖耐量异常、高血压、高三酰甘油血症和低高密度脂蛋白胆固醇血症等代谢紊乱症候群。研究显示,出生体质量异常新生儿在成年期发生代谢性疾病的概率大于出生体质量正常者。出生体质量异常可能会导致儿童及成年期一系列代谢性改变,但目前对于巨大儿及低出生体质量儿发展为儿童代谢综合征的机制还处于探索阶段。与此同时,很多实验研究各自采用不同的儿童代谢综合征的定义,因而难以对这些实验结论做出直接横向比较。文章将分别阐述出生体质量异常与儿童代谢综合征各组分相关性研究进展。