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Background Evidence suggests that LPA risk genotypes are a possible contributor to the clinical diagnosis of familial hypercholesterolemia (FH). This study aimed at determining the prevalence of LPA risk variants in adult individuals with FH enrolled in the Italian LIPIGEN (Lipid Transport Disorders Italian Genetic Network) study, with (FH/M+) or without (FH/M-) a causative genetic variant. Methods and Results An lp(a) [lipoprotein(a)] genetic score was calculated by summing the number risk-increasing alleles inherited at rs3798220 and rs10455872 variants. Overall, in the 4.6% of 1695 patients with clinically diagnosed FH, the phenotype was not explained by a monogenic or polygenic cause but by genotype associated with high lp(a) levels. Among 765 subjects with FH/M- and 930 subjects with FH/M+, 133 (17.4%) and 95 (10.2%) were characterized by 1 copy of either rs10455872 or rs3798220 or 2 copies of either rs10455872 or rs3798220 (lp(a) score ≥1). Subjects with FH/M- also had lower mean levels of pretreatment low-density lipoprotein cholesterol than individuals with FH/M+ (t test for difference in means between FH/M- and FH/M+ groups

Context Nationwide data on children diagnosed with craniopharyngioma (CP) are not available in Italy. Objective This work aimed to identify patients’ characteristics, type of surgical approach, complications and recurrences, number of pituitary deficits, and number of patients starting growth hormone (GH) treatment. Methods A retrospective multicenter collection took place of 145 patients aged 0 to 18 years who underwent surgery for CP between 2000 and 2018, and followed up in 17 Italian centers of pediatric endocrinology. Results Age at diagnosis was 8.4 ± 4.1 years. Duration of symptoms was 10.8 ± 12.5 months and headache was most frequent (54%), followed by impaired growth (48%) and visual disturbances (44%). Most lesions were suprasellar (85%), and histology was adamantinomatous in all cases but two. Surgical approach was transcranial (TC) in 67.5% of cases and transsphenoidal (TS) in 31.%. The TC approach was prevalent in all age groups. Postsurgery complications occurred in 53% of cases, with water-electrolyte disturbances most frequent. Radiotherapy was used in 39% of cases. All patients but one presented with at least one hormone pituitary deficiency, with thyrotropin deficiency most frequent (98.3%), followed by adrenocorticotropin (96.8%), arginine vasopressin (91.1%), and GH (77.4%). Body mass index (BMI) significantly increased over time. A hypothalamic disturbance was present in 55% of cases. GH therapy was started during follow-up in 112 patients at a mean age of 10.6 years, and 54 developed a recurrence or regrowth of the residual lesion. Conclusion CP is often diagnosed late in Italy, with TC more frequent than the TS surgical approach. Postsurgery complications were not rare, and hypopituitarism developed almost in all cases. BMI shows a tendency to increase overtime.

Pathology registers can be a useful tool to overcome obstacles in the identification and management of familial hypercholesterolemia since childhood. In 2018, the LIPIGEN pediatric group was constituted within the Italian LIPIGEN study to focus on FH subjects under 18 years. This work aimed at discussing its recent progress and early outcomes. Demographic, biochemical, and genetic baseline characteristics were collected, with an in-depth analysis of the genetic defects. The analysis was carried out on 1,602 children and adolescents (mean age at baseline 9.9 ± 4.0 years), and almost the whole cohort underwent the genetic test (93.3%). Overall, the untreated mean value of LDL-C was 220.0 ± 97.2 mg/dl, with an increasing gradient from subjects with a negative (N = 317; mean untreated LDL-C = 159.9 ± 47.7 mg/dl), inconclusive (N = 125; mean untreated LDL-C = 166.4 ± 56.5 mg/dl), or positive (N = 1,053; mean untreated LDL-C = 246.5 ± 102.1 mg/dl) genetic diagnosis of FH. In the latter group, the LDL-C values presented a great variability based on the number and the biological impact of involved causative variants. The LIPIGEN pediatric group represents one of the largest cohorts of children with FH, allowing the deepening of the characterization of their baseline and genetic features, providing the basis for further longitudinal investigations for complete details.

Little is known about the role of Lp(a) in the assessment of cardiovascular risk in the paediatric population. Trying to clarify the clinical relevance of Lp(a) in risk stratification, the aim of the study is to evaluate the association between Lp(a) plasma levels in children with familial hypercholesterolaemia (FH) and positive family history for premature cardiovascular disease (pCVD) in first- and second-degree relatives.653 Caucasian children and adolescents (334 females and 319 males), aged 2-17 years, with diagnosis of FH from a paediatric cohort included in the LIPIGEN Network, were selected. We compared family history of pCVD, lipid and genetic profile in two groups based on Lp(a) levels below or above 30 mg/dL. To determine the independent predictors of pCVD, a multivariate logistic regression was used, with all clinical characteristics and blood measurements as predictors.Subjects with Lp(a) 30 mg/dl more frequently reported positive family history of pCVD compared to subjects with Lp(a)≤30 mg/dl (69.90% vs 36.66%, p 0.0001), while did not show differences in terms of median [interquartile range] LDL-cholesterol level (153.00 [88.00 vs 164.50 [90.25] mg/dL, p = 0.3105). In the regression analysis, Lp(a) 30 mg/dl was an independent predictor of family history of pCVD. Comparing subjects with or without family history of pCVD, we reported significant differences for Lp(a) 30 mg/dl (46.25% vs 17.65%, p 0.0001), FH genetic mutation (50.48% vs 40.75%, p = 0,0157), as well as for LDL-cholesterol (p = 0.0013) and total cholesterol (p = 0.0101).Children/adolescents with FH and Lp(a) 30 mg/dl where more likely to have a positive family history of pCVD. Lp(a) screening in children and adolescents with FH may enhance risk assessment and help identify those subjects, children and relatives, at increased pCVD risk.

In the last few decades, many studies have reported an increasing global incidence of type 1 diabetes. Studies on migrant populations have underlined the importance of both environmental and genetic factors.Evaluate the incidence of type 1 diabetes in North African vs Italian children aged 0-14 years from 1 January 2015, to 31st December 2018, in Emilia-Romagna region, Italy.Clinical and epidemiological data about childhood onset type 1 diabetes in Emilia Romagna region were retrospectively collected by the regional centers of pediatric diabetology and matched using 3 different data sources.365 new cases were diagnosed. Total cumulative incidence was 15.4/100,000/year. North African cases showed a cumulative incidence of 53.8/100,000/year, statistically significant compared to cumulative incidence of the Italian cases alone 13.1/100,000/year (p value 0.001). The annual incidence did not differ in the 4 years for both groups. Conclusion: The incidence of type 1 diabetes in the pediatric age (0 14 years) was significantly higher in the North African population than in the Italian one, suggesting that a mix of genetic and environmental factors may have caused the increase in newly diagnosed cases.• The incidence of type 1 diabetes largely varies worldwide. • Study on immigrants helped to better understand the interplay role between genetics and environment.• This is the first study focused on the incidence of children and adolescents of North African migrants in Italy. • The incidence of children and adolescents of North African migrants in Emilia Romagna region, Italy, seems to be higher than that reported in the host countries, and, above all, than that reported in highest-incidence countries in Europe and in the world.

Background X-linked Adrenal Hypoplasia Congenita (AHC) is a rare cause of primary adrenal insufficiency due to mutations in the NR0B1 gene, causing a loss of function of the nuclear receptor protein DAX-1. Adrenal insufficiency usually appears in the first 2 months of life, but can sometimes emerge during childhood. Hypogonadotropic Hypogonadism is often associated later in life and patients may develop azoospermia. We describe an unusual onset of AHC started with isolated hypoaldosteronism as first and only sign of the disease. Case presentation A 18-days-old newborn presented with failure to thrive and feeding difficulties. Blood tests showed severe hyponatremia, hyperkalemia and hypochloremia. Renin was found over the measurable range and aldosterone was low whereas cortisol level was normal with a slightly increased ACTH. In the suspicion of Primary Hypoaldosteronism, correction of plasmatic electrolytes and replacement therapy with Fludrocortisone were promptly started. The subsequent evidence of low plasmatic and urinary cortisol and increased ACTH required the start of Hydrocortisone replacement therapy and it defined a clinical picture of adrenal insufficiency. Genetic analysis demonstrated a novel mutation in the DAX-1 gene leading to the diagnosis of AHC. Conclusions AHC onset may involve the aldosterone production itself, miming an isolated defect of aldosterone synthesis. NR0B1/DAX-1 mutations should be considered in male infants presenting with isolated hypoaldosteronism as first sign of adrenal insufficiency.

Introduction One aim of the long-term care in survivors from acute lymphoblastic leukemia (ALL) during childhood is to avoid or limit complications caused by aggressive therapeutic strategies. Areas covered ALL survivors are a heterogeneous group according to therapeutic protocols. In the last decades, cranial radiotherapy (cRT) has been largely replaced by intrathecal chemotherapy (CT) with a reduction of endocrine sequelae. Published studies are generally difficult to be interpreted because patients were treated according to different risk-adapted protocols and results are conflicting. We perform this review on endocrine long-term effects in childhood ALL survivors focusing on studies published in the last decades. Articles were selected using the following terms (Mesh terms): 'acute lymphoblastic leukemia' AND 'survivors' AND 'childhood' AND 'growth/puberty/fertility/obesity/metabolic syndrome/bone'. Expert commentary Most childhood ALL survivors treated with CT alone attain normal height and have adequate pubertal development. Despite recent protocols improvements, ALL survivors still develop long-term metabolic complications (overweight, obesity, and cardiovascular disease) especially the female gender and patients with an increased body mass index (BMI) at diagnosis. The aim of this review is to describe the state of the art on these topics. We should be able to anticipate, prevent, and treat endocrine long-term morbidities through a well-established follow-up strategy.

Background/Aims: Obesity is a multifactorial disease caused by the interaction of genetic, environmental, and behavioral factors. Currently, only a small number of obese children undergo genetic analysis, usually when obesity is associated with dysmorphic features. The aim of this study was to identify genomic rearrangement causing obesity. Methods: We analyzed the DNA of children and adolescents by single-nucleotide polymorphism-array (platform CytoScan HD, Affymetrix). Patients included in this study were obese with dysmorphic features and/or intellectual disabilities and/or neuropsychomotor signs. Results: Ninety-four children and adolescents with obesity (9.25 ± 4.04 years old, 60 males) were enrolled in the study. Dysmorphic features were found in 64 out of 94 subjects (68.1%), intellectual disability was found in 23 subjects (24.5%), and other neuropsychomotor signs in 31 (32.9%). Copy number variations (CNVs) were identified in 43 out of 94 patients (45.7%): among these 14 subjects showed at least 1 deletion, 22 duplication, whereas 7 patients showed both deletion and duplication. In 20 subjects (13 males), CNVs were linked or possibly related with obesity; in 23 subjects, this correlation cannot be inferred. Conclusion: A genetic origin of obesity was detected in about half of our obese children and adolescents with associated dysmorphic features and/or intellectual disability and/or neuropsychomotor signs. In these children, array-CGH analysis can be useful to identify causative genetic mutations, with consequent advantage in therapeutic management and follow-up of these patients.

Objective Transient neonatal diabetes mellitus (TNDM) is caused by activating mutations in ABCC8 and KCNJ11 genes (KATP/TNDM) or by chromosome 6q24 abnormalities (6q24/TNDM). We wanted to assess whether these different genetic aetiologies result in distinct clinical features. Design Retrospective analysis of the Italian data set of patients with TNDM. Methods Clinical features and treatment of 22 KATP/TNDM patients and 12 6q24/TNDM patients were compared. Results Fourteen KATP/TNDM probands had a carrier parent with abnormal glucose values, four patients with 6q24 showed macroglossia and/or umbilical hernia. Median age at diabetes onset and birth weight were lower in patients with 6q24 (1 week; −2.27 SD) than those with KATP mutations (4.0 weeks; −1.04 SD) (P = 0.009 and P = 0.007, respectively). Median time to remission was longer in KATP/TNDM than 6q24/TNDM (21.5 weeks vs 12 weeks) (P = 0.002). Two KATP/TNDM patients entered diabetes remission without pharmacological therapy. A proband with the ABCC8/L225P variant previously associated with permanent neonatal diabetes entered 7-year long remission after 1 year of sulfonylurea therapy. Seven diabetic individuals with KATP mutations were successfully treated with sulfonylurea monotherapy; four cases with relapsing 6q24/TNDM were treated with insulin, metformin or combination therapy. Conclusions If TNDM is suspected, KATP genes should be analyzed first with the exception of patients with macroglossia and/or umbilical hernia. Remission of diabetes without pharmacological therapy should not preclude genetic analysis. Early treatment with sulfonylurea may induce long-lasting remission of diabetes in patients with KATP mutations associated with PNDM. Adult patients carrying KATP/TNDM mutations respond favourably to sulfonylurea monotherapy.

Purpose: To assess subclinical markers of endothelial inflammation in young survivors from acute lymphoblastic leukemia (ALL) treated with chemotherapy without cranial irradiation. Methods: Anthrop...

OBJECTIVE To determine if the diabetes-specific health-related quality of life (D-HRQOL) of young people with type 1 diabetes (T1D) and their parents is influenced by migrant status. SUBJECTS AND METHODS One hundred and twenty-five patients (12.4 ± 3.55 years, males 53.6%) with T1D and their parents (102 mothers, 37 fathers) were enrolled and categorized into: group A (both foreign parents) and group B (both native Italian parents). The Pediatric Quality of Life Inventory™ 3.0 Diabetes Module (PedsQL™ 3.0 DM) was used to evaluate the D-HRQOL. Data on diabetic ketoacidosis (DKA) at T1D onset, insulin therapy, and glycosylate hemoglobin (HbA1c) were also collected. RESULTS Group A (n = 40), compared to group B (n = 85), had higher frequency of DKA at T1D onset (P

Background and aims Severe hypercholesterolemia associated or not with xanthomas in a child may suggest the diagnosis of homozygous autosomal dominant hypercholesterolemia (ADH), autosomal recessive hypercholesterolemia (ARH) or sitosterolemia, depending on the transmission of hypercholesterolemia in the patient's family. Sitosterolemia is a recessive disorder characterized by high plasma levels of cholesterol and plant sterols due to mutations in the ABCG5 or the ABCG8 gene leading to a loss of function of the ATP-binding cassette (ABC) heterodimer transporter G5-G8. Methods We aimed to perform the molecular characterization of two children with severe primary hypercholesterolemia. Results Case #1 was a 2 year-old girl with high LDL-cholesterol (690 mg/dl) and tuberous and intertriginous xanthomas. Case #2 was a 7 year-old boy with elevated LDL-C (432 mg/dl) but no xanthomas. In both cases, at least one parent had elevated LDL-cholesterol level. For molecular diagnosis, we applied targeted next generation sequencing (NGS), which unexpectedly revealed that both patients were compound heterozygous for nonsense mutations: Case #1 in ABCG5 gene [p.(Gln251*)/p.(Arg446*) ] and Case #2 in ABCG8 gene [p.(Ser107*)/p.(Trp361*)]. Both children had extremely high serum sitosterol and campesterol levels, thus confirming the diagnosis of sisterolemia. A low-fat/low-sterol diet was promptly adopted with and without the addition of ezetimibe for Case #1 and Case #2, respectively. In both patients, serum total and LDL-cholesterol decreased dramatically in two months and progressively normalized. Conclusions Targeted NGS allows the rapid diagnosis of sitosterolemia in children with severe hypercholesterolemia, even though their family history does not unequivocally suggest a recessive transmission of hypercholesterolemia. A timely diagnosis is crucial to avoid delays in treatment.

Background Children with Sickle Cell Disease (SCD) show endocrine complications and metabolic alterations. The physiopathology of these conditions is not completely understood: iron overload due to chronic transfusions, ischemic damage, and inflammatory state related to vaso-occlusive crises may be involved. Aims of this study were to evaluate the growth pattern, endocrine complications, and metabolic alterations and to detect the relationship between these conditions and the SCD severity in affected children and adolescents. Methods Fifty-two children and adolescents with SCD [38 homozygous sickle hemoglobin (HbSS) and 14 heterozygous sickle hemoglobin (HbSC); age range 3–18 years] were recruited. Anthropometric [height, body mass index (BMI), arm span, sitting height, target height (TH), and pubertal status] and laboratory [blood cell counts, hemolysis indices, metabolic and nutritional status indices and hormonal blood levels] data were evaluated. The SCD severity was defined according to hematological and clinical parameters. Results Height-SDS adjusted for TH and BMI-SDS were significantly higher in HbSC children than in HbSS ones. Forty-eight out of 52 patients (92%) had at least one metabolic and/or endocrine alteration: insufficiency/deficiency of vitamin D (84.7%), insulin resistance (11.5%), growth hormone deficiency (3.8%), subclinical hypothyroidism (3.8%), and hypogonadism (1.9%). Levels of vitamin D were significantly and negatively correlated with clinical indicators of the SCD severity. Subjects with HbSS genotype show significant lower levels of both insulin-like growth factor-1 (IGF-1) and insulin-like growth factor binding protein 3 than children with HbSC. In the study population IGF-1 values were significantly and positively correlated with Hb and negatively with lactate dehydrogenase. Conclusions Metabolic alterations and endocrine complications are very common in children and adolescents with SCD. A regular follow-up is necessary to identify subjects at risk for complications to precociously start an appropriate treatment and to improve the quality of life of SCD patients. Electronic supplementary material The online version of this article (10.1186/s12887-019-1423-9) contains supplementary material, which is available to authorized users.

The diagnosis of dyslipidemia is increasing both in adulthood and in childhood because of not only the steadily increasing prevalence of obesity but also a rise of medical attention in detecting unfavorable genetic conditions in patients of all ages. Attempts in lifestyle changes are frequently failing and thus the pharmacological treatment of dyslipidemia is spreading in medical practice to reduce cardiovascular risk. In childhood, statins are authorized by 8 years of age. Nevertheless, data on their long-term safety and efficacy are still lacking, especially in ones with high cardiovascular risk and/or primary dyslipidemia such as homozygous familial hypercholesterolemia, considerable as a mainly exclusively pediatric disease. Thus, new pharmacological approaches are needed and have to be evaluated in all categories of patients. In this context, the update and the critical revision of new medications have become a new duty for scientists and clinicians.

Atherosclerosis represents a disease that begins in childhood, and alterations in lipid concentration play a fundamental role in the development of this condition. Children and adolescents with high cholesterol levels are more likely than their peers in the general population to present with dyslipidemia in adulthood. Precocious identification of dyslipidemias associated with premature cardiovascular disease is crucial during childhood to delay or prevent the atherosclerotic process. The National Cholesterol Education Program has established guidelines for the diagnosis and treatment of dyslipidemia during pediatric age. It has been suggested that a heart-healthy diet should begin at 2 years of age, and no adverse effects on psychological aspects, growth, pubertal development and nutritional status in children and adolescents limiting total and saturated fat intake have been demonstrated. Pharmacotherapy should be considered in children aged 10 years or older when low-density lipoprotein cholesterol concentrations remain very high despite dietary therapy, especially when multiple risk factors are present. The lipid-lowering drugs recommended for childhood and adolescence are resins and statins. The increasing use of statins is dependent on their effectiveness and safety. Ezetimibe, a selective cholesterol absorption inhibitor, may provide a similar cholesterol-lowering effect as that reached with statin treatment. This review provides an update on recent advances in the therapy of dyslipidemia, especially hypercholesterolemia, during pediatric age and adolescence.

Aims To evaluate physicians' adjustments of insulin pump settings based on continuous glucose monitoring (CGM) for patients with type 1 diabetes and to compare these to automated insulin dose adjustments. Methods A total of 26 physicians from 16 centres in Europe, Israel and South America participated in the study. All were asked to adjust insulin dosing based on insulin pump, CGM and glucometer downloads of 15 patients (mean age 16.2 ± 4.3 years, six female, mean glycated haemoglobin 8.3 ± 0.9% [66.8 ± 7.3 mmol/mol]) gathered over a 3-week period. Recommendations were compared for the relative changes in the basal, carbohydrate to insulin ratio (CR) and correction factor (CF) plans among physicians and among centres and also between the physicians and an automated algorithm, the Advisor Pro (DreaMed Diabetes Ltd, Petah Tikva, Israel). Study endpoints were the percentage of comparison points for which there was full agreement on the trend of insulin dose adjustments (same trend), partial agreement (increase/decrease vs no change) and full disagreement (opposite trend). Results The percentages for full agreement between physicians on the trend of insulin adjustments of the basal, CR and CF plans were 41 ± 9%, 45 ± 11% and 45.5 ± 13%, and for complete disagreement they were 12 ± 7%, 9.5 ± 7% and 10 ± 8%, respectively. Significantly similar results were found between the physicians and the automated algorithm. The algorithm magnitude of insulin dose change was at least equal to or less than that proposed by the physicians. Conclusions Physicians provide different insulin dose recommendations based on the same datasets. The automated advice of the Advisor Pro did not differ significantly from the advice given by the physicians in the direction or magnitude of the insulin dosing.

Background. Children affected by neurodevelopmental disability could experience early pubertal changes at least 20 times more than the general population. Limited data about central precocious puberty (CPP) among children affected by cerebral palsy (CP) are available. Methods. This is a longitudinal, observational, retrospective, case-control study involving 22 children affected by CPP and CP (group A), 22 paired with CP but without CPP (group B), and 22 children with CPP without CP. Auxological, biochemical, and instrumental data were collected at diagnosis of CPP and at 2 follow-up visits. Results. No differences were detected between groups A (at baseline) and B. At diagnosis of CPP, height SDS adjusted for target height (H-TH SDS) was significantly reduced in A than in C (−0.63 ± 1.94 versus 1.56 ± 1.38), while basal LH and oestradiol levels were significantly elevated in A than in C. During follow-up, despite an effective treatment, growth impairment deteriorated in A than in C (Δ H-SDS from diagnosis of CPP to last follow-up: −0.49 ± 0.91 versus 0.21 ± 0.33, p=0.023). Conclusions. Diagnosis of CPP could be partially mislead in CP due to growth failure that got worse during follow-up despite therapy. CPP in CP seems to progress rapidly along time supporting the hypothesis of a more intense activation of hypothalamic-pituitary-gonadal-axis in these patients.

Background: Obesity is associated with chronic low-grade inflammation and hyperinsulinism that may influence the progression of endothelial dysfunction and atherosclerosis already in childhood. Methods: To study changes in metabolic profile and markers of inflammation and endothelial activation in children with primary severe obesity after weight loss we involved 14 obese children (Ob) that underwent a lifestyle intervention and 18 normal weighted subjects (C). In Ob, anthropometric data were assessed both at baseline and after intervention together with oral glucose tolerance test and fasting evaluation of cholesterol assessment, interleukin-6, endogenous secretory receptor of advanced glycation end products and endothelin levels. Results: At baseline, serum IL-6 concentrations resulted significantly higher in Ob respect to C (12.96 ± 8.87 vs. 4.88 ± 1.19 pg/ml, p< 0.05). After weight loss, Ob significantly improved glucose metabolism and lipid assessment and they showed a significant reduction of all markers of inflammation and endothelial activation. In all subjects studied, BMI-SDS correlated positively with interleukin-6 (r 0.45, p < 0.05). Conclusion: Our results demonstrated higher concentrations of inflammatory markers in obese children compared to healthy subjects. Nevertheless, an early lifestyle intervention could improve the levels of these molecules together with cholesterol and glucose metabolism and may reverse the development of premature endothelial dysfunction in obese children.

Background/Aims: The natural history of thyroid function in children with Down's syndrome is relatively unknown. We hypothesized that in these patients the occurrence of thyroid dysfunction rises during development. Methods: Thyroid function was assessed yearly in 145 children with Down's syndrome, all followed from birth up to 10 years of age. Heteroskedastic binary and ordinary logistic regression for repeated measures was used to evaluate the relationship of thyroid function with continuous time. Results: Congenital hypothyroidism was detected in 7% of cases. The probability of acquired thyroid dysfunction increased from 30% at birth to 49% at 10 years (p < 0.001). The subclinical hypothyroidism was nearly stable during the follow-up. The probability of hypothyroidism increased from 7 to 24% at 10 years (p < 0.001). Positive anti-thyroglobulin antibodies were associated with higher odds of more severe hypothyroidism (odds ratio 3.6). Positive anti-thyroid peroxidase antibodies were a better predictor of more severe hypothyroidism (odds ratio 6.1). Diffuse hypoechogenicity on thyroid ultrasound was found in 34 out of 145 children. Conclusion: The probability of thyroid dysfunction increasing during development is higher than previously reported. Such children should be carefully monitored annually to early identify thyroid dysfunction.

Objective: The accuracy of the SenseWear Pro2 Armband (SWA) in estimating resting energy expenditure (REE) in children and adolescents with obesity, using indirect calorimetry (IC) as a reference was evaluated. Design and Methods: REE was assessed using both the SWA and IC in 40 obese subjects (26 M/14 F, age 11.5 ± 2.57 years, z-score BMI 3.14 ± 0.53). The agreement between methods was assessed by the Bland-Altman procedure. The relationship between REE assessments and patients' characteristics was also analyzed. Results: SWA- and IC-derived estimates of REE showed a significant correlation (r = 0.614; P < 0.001), but the SWA overestimated mean REE by 13% (P < 0.001). Age and kilogram of fat-free mass (kg-FFM) were significantly correlated with both REE estimation by SWA (r = 0.434 and r = 0.564, respectively) and IC (r = 0.401 and r = 0.518, respectively). Only kg-FFM was demonstrated to be the main predictor factor of REE variability (r2 79% SWA; 75% IC). Conclusions: The SWA overestimated mean REE in childhood obesity, suggesting that the SWA and IC are not yet interchangeable methods. This would require improving the SWA by developing better algorithms for predicting REE and, probably, bias in each individual REE could be reduced by an adjustment for subjects' kg-FFM.

Background: Few large, long-term studies are available on the relationship between childhood and adult obesity. Aim: The present study examined the 30-year association between childhood and adult obesity in a large sample of girls with essential and uncomplicated obesity. Subjects and methods: 318 girls who had visited our Pediatric Obesity Clinic between January 1972 and December 1974 were re-contacted between January 2002 and December 2005. All had undergone an assessment of weight, height and pubertal status at the baseline visit. Anthropometry was performed again on those who agreed to take part in the follow-up visit. The women’s general practitioners were also asked to compile a health questionnaire. Hypertension, hypercholesterolemia, hypertriglyceridemia and diabetes were defined according to current guidelines. Rates are expressed as number of cases per 1000 person-years (PY). Multivariable Poisson regression was used to identify predictors of persistent obesity. Results: 224 (70%) of the 318 girls took part to the 30-year follow-up study. They had the same baseline anthropometry of those not available at follow-up. Sixteen per cent of them were still obese at the 30-year follow-up, giving a persistence rate of obesity of 5.2 � 1000 PY. Tanner stages � 1 [rate ¼ ratios (RR) from 4.73 to 7.74 for different stages, p � 0.021] and Z-score of BMI (RR ¼ 2.72 for one SDS, p ¼ 0.019) were independent predictors of obesity persistence. Having a university degree vs. an elementary degree was instead protective (RR ¼ 0.32, p ¼ 0.009). The most prevalent complication was hypertriglyceridemia (8.8 � 1000 PY), followed by hypercholesterolemia (rate ¼ 8.4 � 1000 PY), hypertension (rate ¼ 5.2 � 1000 PY) and diabetes mellitus (rate ¼ 1.0 � 1000 PY). Conclusion: The study reinforces the notion that obesity should be prevented at an early age and shows that adolescents with severe obesity and low educational degree are at greater risk of becoming obese adults.

Background. Impairments of endocrine system may be associated with exposure to perfluorinated compounds that are able to bind nuclear receptors, including the peroxisome proliferator-activating receptors. Aim of this study was to assess perfluorooctane sulfonate and perfluorooctanoic acid concentrations in children and adolescents at the onset of type 1 diabetes compared to healthy controls.Methods. Forty-four children and adolescents were recruited and subdivided into two groups: (A) 25 subjects with type 1 diabetes and (B) 19 healthy controls. Perfluorinated compounds were measured using high performance liquid chromatography with electrospray ionization tandem mass spectrometry. Nonparametric statistical analysis was performed.Results. Perfluorooctane sulfonate concentrations were significantly higher in patients with type 1 diabetes compared to controls (1.53 ± 1.50 versus 0.55 ± 0.15 ng/mL, resp.;p<0.001). Multivariate linear regression analysis identified lipid levels as significant predictive factors for perfluorooctane sulfonate levels.Conclusions. Our data suggests that higher serum levels of perfluorooctane sulfonate may be considered a biomarker of exposure and susceptibility to develop type 1 diabetes.

Type 1 diabetes (T1DM) predisposes to cardiovascular disease, increasing the risk to develop atherosclerosis. In the pediatric population, the cardiovascular risk may be evaluated examining endothelial function by a non-invasive ultrasound technique, namely flow-mediated dilation (FMD) of the brachial artery. The aims of this study were the longitudinal evaluation of the potential change in the endothelium-dependent vasomotor function in children and adolescents with T1DM and the identification of clinical and laboratory data correlated to modifications.We studied 39 T1DM patients (20 girls and 19 boys; aged 11.2 ± 3.72 years). FMD and blood samples were obtained from all patients at baseline (time 0) and after a follow up of at least 1 year (time 1). FMD was also evaluated in 45 healthy controls (22 boys, 23 girls) aged 10.2 ± 3.05 years.At time 0, 43.6% of T1DM patients presented an impaired FMD. FMD at time 1 revealed a dramatic impairment of endothelial function: altered FMD values were shown in 61.5% of patients and it got worse in 74.3% of them. Longitudinally, boys had a greater impairment of FMD than girls. At baseline, multivariate analysis identified only sex as significant predictor of FMD (β = 0.470, P = 0.029).Because endothelial dysfunction appears earlier in diabetic children, they are at higher risk to develop atherosclerosis. Our results suggest the usefulness of FMD as a tool to stratify pediatric T1DM patients according to their cardiovascular risk and to follow them up longitudinally.

The accuracy of the SenseWear Pro2 Armband (SWA) in estimating resting energy expenditure (REE) in children and adolescents with obesity, using indirect calorimetry (IC) as a reference was evaluated.REE was assessed using both the SWA and IC in 40 obese subjects (26 M/14 F, age 11.5 ± 2.57 years, z-score BMI 3.14 ± 0.53). The agreement between methods was assessed by the Bland-Altman procedure. The relationship between REE assessments and patients' characteristics was also analyzed.SWA- and IC-derived estimates of REE showed a significant correlation (r = 0.614; P0.001), but the SWA overestimated mean REE by 13% (P0.001). Age and kilogram of fat-free mass (kg-FFM) were significantly correlated with both REE estimation by SWA (r = 0.434 and r = 0.564, respectively) and IC (r = 0.401 and r = 0.518, respectively). Only kg-FFM was demonstrated to be the main predictor factor of REE variability (r(2) 79% SWA; 75% IC).The SWA overestimated mean REE in childhood obesity, suggesting that the SWA and IC are not yet interchangeable methods. This would require improving the SWA by developing better algorithms for predicting REE and, probably, bias in each individual REE could be reduced by an adjustment for subjects' kg-FFM.

Acute lymphoblastic leukemia is the most common malignancy in childhood. Continuous progress in risk-adapted treatment for childhood acute lymphoblastic leukemia has secured 5-year event-free survival rates of approximately 80% and 8-year survival rates approaching 90%. Almost 75% of survivors, however, have a chronic health condition negatively impacting on cardiovascular morbidity and mortality. Obesity can be considered one of the most important health chronic conditions in the general population, with an increasing incidence in patients treated for childhood cancers and especially in acute lymphoblastic leukemia survivors who are, at the same time, more at risk of experiencing precocious cardiovascular and metabolic co-morbidities. The hypothalamic-pituitary axis damage secondary to cancer therapies (cranial irradiation and chemotherapy) or to primary tumor together with lifestyle modifications and genetic factors could affect long-term outcomes. Nevertheless, the etiology of obesity in acute lymphoblastic leukemia is not yet fully understood. The present review has the aim of summarizing the published data and examining the most accepted mechanisms and main predisposing factors related to weight gain in this particular population.

To review the recent findings on evaluation and management of dyslipidemia in childhood and adolescence, giving a critical view on new therapeutic approaches.In 2008, the American Academy of Pediatrics released an updated policy statement recommending more frequent screening to detect dyslipidemia in childhood and the first-line use of statins in children with dyslipidemia who did not respond to lifestyle intervention and who were more than 8 years of age. These recommendations have caused a lot of controversy within the medical community and media. This debate is also sharpened by the fact that only few trials have investigated the long-term efficacy of statins on prevention of adult cardiovascular disease, their application in dyslipidemias other than familial hypercholesterolemia and the use of new pharmacological tools.The purpose of our paper could not be achieved clearly without a review of the physiology of cholesterol metabolism together with an analysis of causes of primary and secondary dyslipidemia affecting children. Moreover, recent knowledge on lipid-lowering therapy is reviewed.

Prader-Willi syndrome (PWS), a genetic disorder due to an alteration in the paternally derived long arm of chromosome 15, is characterized by a complex clinical picture (short stature, obesity, hypogonadism) that seems to be referable to as a central hypothalamic/pituitary dysfunction. To determine whether there is any diminution in the anterior pituitary gland or other neuroradiological alterations, we retrospectively analysed 91 patients with PWS (42 females, 49 males; age range: 0.7-16.8 years) by cerebral magnetic resonance imaging (MRI). Of these 91 patients, MRI analysis showed a reduction in pituitary height in 45 patients (49.4%), a complete absence of the posterior pituitary bright spot in six patients (6.6%) and other neuroradiological alterations in ten patients (11%). Altogether, neuroradiological alterations were present in 61 of the 91 (67%) patients. Our results indicate that neuroradiological alterations are more frequent in PWS patients than has been reported to date.

Background Young adult survivors of childhood acute lymphoblastic leukemia (ALL) treated with protocols including cranial radiotherapy demonstrate a persistent weight gain and reduced final height. Published reports on the effects on growth of different oncologic therapies are conflicting and difficult to interpret because they combined children treated with both cranial irradiation and multi-agent chemotherapy. Our study investigated the effect of chemotherapy alone on body mass index (BMI) and on growth at the achievement of final height in a homogeneous cohort of Italian childhood ALL survivors. Methods We retrospectively studied 162 Caucasian patients treated on the Italian Association of Pediatric Hematology and Oncology protocols without radiotherapy between 1989 and 2000 at five Italian centers with 107 inclusions (58 males). Height- and BMI-standard deviation score (SDS) were collected at diagnosis of ALL, at the end of treatment and at the achievement of final height. Changes in height SDS and BMI SDS with time were analyzed using dependent sample Student's t-test. Results A significant reduction of height-SDS was documented during treatment in both genders. This reduction of height-SDS was not followed by an appropriate catch-up growth, despite the achievement of a mean final height within the normal range. At diagnosis females showed a lower mean BMI-SDS than males. During treatment, in the whole population, BMI-SDS increased significantly. After it, while males lost BMI-SDS, females showed its persistent increase. Conclusions Survivors of childhood ALL generally seemed to achieve a normal final height with a BMI within the normal range. These parameters appeared to be only minimally affected by chemotherapy. Nevertheless, height catch-up growth was not completed after chemotherapy in both genders and all patients experienced an increase of BMI-SDS during chemotherapy that only females seemed to conserve until the achievement of final height.

Background Rosai-Dorfman disease (RDD) is a rare form of histiocytosis characterized by histiocyte proliferation within lymph nodes and extranodal tissue. Here we report an unusual presentation of RDD in an Italian toddler. Moreover, we reviewed the pediatric case reports published between 2004 and 2014, focusing in particular on medical therapy. Case presentation We report the case of a 14-month-old child who developed a progressive swelling of the right parotid, associated with systemic symptoms and abnormal blood tests. During diagnostic work-up, cervical, intraparotid, and unilateral hilar lymphadenopathies were found. Histopathological and immunohistochemistry studies of a cervical lymph node biopsy established the diagnosis of RDD, with positive PCR for Epstein - Barr virus on the biopsy specimen. Oral steroid therapy was started with progressive reduction in size of all lesions, resolution of systemic symptoms, and normalization of blood tests. Conclusion RDD is generally considered a benign and self-limiting form of histiocytosis, usually associated with favorable prognosis. However, complications are not infrequent and fatal cases were reported even in children. Efforts should be made to establish the best therapeutic strategy for this disease, as no well-defined guidelines exist. Finally, RDD should be included in differential diagnosis of lymphadenopathy and parotid swelling even in very young children. Electronic supplementary material The online version of this article (doi:10.1186/s12887-016-0595-9) contains supplementary material, which is available to authorized users.

An epidemic of pediatric obesity has occurred across the world in recent years. There are subgroups within the population at high-risk of becoming obese and especially of having experience of precocious cardiovascular and metabolic co-morbidities of obesity. One of these subgroups comprises patients treated for childhood cancers and namely survivors of craniopharyngioma. The high incidence of obesity in this group makes these patients an important disease model to better understand the metabolic disturbances and the mechanisms of weight gain among cancer survivors. The hypothalamic-pituitary axis damage secondary to cancer therapies or to primary tumor location affect long-term outcomes. Nevertheless, the aetiology of obesity in craniopharyngioma is not yet fully understood. The present review has the aim of summarizing the published data and examining the most accepted mechanisms and main predisposing factors related to weight gain in this particular population.