A 343 Italian cohort of patients analysed with array-comparative genomic hybridization: unsolved problems and genetic counselling difficulties.

BACKGROUND: The recent introduction of microarrays for genetic analyses has allowed higher etiological diagnostic rates in patient with intellectual disability (ID), autism spectrum disorders (ASD), epilepsy and multiple congenital anomalies (MCA), because of its resolution. This approach still results of high complexity and some limitations have been reported. In fact, it discloses several variants of unknown significance (VOUS) or incidental findings. In all cases, a massive amount of data is generated, because of this, the analysis and the interpretation is very difficult and often without a definitive conclusion. METHOD: We analysed an Italian cohort of 343 patients with ID, MCA and ASD by array-comparative genomic hybridization. The purpose of this work was to consider the proportion of the chromosomal abnormalities in such cohort and to assess the distribution of the different type of the chromosomal abnormalities concerning their pathogenic significance, their origin and their correlation to these clinical phenotypes. RESULTS: Array-comparative genomic hybridization analysis revealed 76 positive results. Abnormalities were detected in 27.8% of patients with ID, 11.1% with ASD, 10.7% with epilepsy and 19.4% with multiple congenital anomalies. The anomalies were classified in three major groups: group 1 (27 patients) with pathogenic alterations (P group); group 2 (34 patients) with VOUS potentially pathogenic (PP group); and group 3 (13 patients) with VOUS potentially benign (PB group). As expected, comparing the diagnostic groups, we observed a greater number of deletions in the P group and that all the abnormalities of the PB group were inherited. CONCLUSIONS: Our retrospective study resulted in confirming the high detection rate of microarrays. CNV classification remains a complex procedure. The difficulty in CNV classification points out the importance of the patient selection, helping the interpretation of the molecular cytogenetic results.

Food protein-induced enterocolitis syndrome in children: what's known? What's new?

Summary: Food protein-induced enterocolitis syndrome (FPIES) is an under-recognized and frequently misdiagnosed non-IgE mediated food allergy syndrome. Affected infants show gastrointestinal symptoms few hours after ingestion of the incriminating food. Pathophysiology of FPIES has not yet been clearly defined and needs further characterization. The common allergy tests are not helpful for this disorder and tests for food specific IgE are usually negative. A diagnostic oral food challenge (OFC) is the method to confirm the diagnosis of FPIES. This review summarizes what is known about epidemiology, pathophysiology, clinical characteristics and diagnosis and what's new about therapeutic options of FPIES.

Validation of the Italian Quality of Life in Short Stature Youth (QoLISSY) questionnaire.

PURPOSE: The Quality of Life in Short Stature Youth (QoLISSY) questionnaire is a disease-specific instrument developed to assess health-related quality of life (HrQoL) in children with short stature. While the original instrument was simultaneously developed in five European countries, this study describes the results of the Italian QoLISSY translation, cultural adaptation, and validation. METHODS: Focus group discussions and a cognitive debriefing process with children (N = 12) diagnosed with growth hormone deficiency or idiopathic short stature and one parent each, as well as parents of younger children (N = 20) were conducted to examine the linguistic and content validity of the Italian version. Psychometric testing was performed using data from the subsequent field- and re-test (N = 32). RESULTS: The results of the qualitative testing of the Italian sample revealed comparability of content to data of the original five European countries. The following field- and re-test results were psychometrically satisfactory including good item and scale operating characteristics, sufficient evidence of reliability, and acceptable evidence of construct validity. CONCLUSION: In conclusion, the Italian QoLISSY HrQoL-dimensions are comparable to other European countries. The psychometric quality of the Italian QoLISSY version is satisfactory and the instrument is ready for use in Italian patients and their parents.

One-hour post-load plasma glucose levels associated with decreased insulin sensitivity and secretion and early makers of cardiometabolic risk.

PURPOSE: Obese adults with normal glucose tolerance (NGT) but with 1-hour post-load plasma glucose (1hPG) ≥ 155 mg/dl are at higher risk of developing type 2 diabetes (T2D) and cardiometabolic complications. Little information is available for the pediatric population, where recently, a lower cutoff, 132.5 mg/dl, has been suggested as being more sensitive to identify subjects at risk of T2D. Our aim was to assess whether obese Caucasian youth with 1hPG ≥ 132.5 mg/dl have worse insulin sensitivity and secretion and a worse cardiometabolic profile compared to obese youth with 1hPG < 132.5 mg/dl. METHODS: Medical records of 244 (43% male; age: 11.1 ± 2.7years) overweight/obese children and adolescents, who had undergone an oral glucose tolerance test (OGTT), were retrieved. Anthropometric and biochemical data were collected from the hard copy archive. Indexes of insulin resistance (HOMA-IR), insulin sensitivity (WBISI), and insulin secretion (Insulinogenic Index, Disposition Index) were calculated. RESULTS: Of the 244 records analyzed, 215 fulfilled criteria for NGT and had complete biochemical data. Among NGT patients, 42 (19.5%) showed 1hPG ≥ 132.5 mg/dL (high-NGT), while the remaining had 1hPG < 132.5 mg/dL (low-NGT). The high-NGT group showed a higher male prevalence (59.5 vs 37%), lower Disposition Index (0.54 [0.39-0.71] vs 0.79 [0.47-1.43]), and WBISI (0.24 [0.18-0.35] vs 0.33 [0.23-0.50]) than the low-NGT group. High-NGT subjects also showed a trend towards lower HDL-cholesterol and higher triglycerides/HDL-cholesterol ratio (2.13 [1.49-3.41] vs 1.66 [1.24-2.49]). CONCLUSIONS: In overweight/obese NGT Caucasian youth a 1hPG ≥ 132.5 mg/dL was able to identify those with impaired insulin sensitivity and secretion and a trend towards a worse cardio-metabolic profile, a group likely at risk for future T2D.

Association between markers of endothelial dysfunction and early signs of renal dysfunction in pediatric obesity and type 1 diabetes.

BACKGROUND: To evaluate whether circulating markers of endothelial dysfunction, such as intercellular adhesion molecule-1 (ICAM-1) and myeloperoxidase (MPO), are increased in youth with obesity and in those with type 1 diabetes (T1D) at similar levels, and whether their levels are associated with markers of renal function. METHODS: A total of 60 obese youth [M/F: 30/30, age: 12.5 ± 2.8 yr; body mass index (BMI) z-score: 2.26 ± 0.46], 30 with T1D (M/F: 15/15; age: 12.9 ± 2.4 yr; BMI z-score: 0.45 ± 0.77), and 30 healthy controls (M/F: 15/15, age: 12.4 ± 3.3 yr, BMI z-score: -0.25 ± 0.56) were recruited. Anthropometric measurements were assessed and a blood sample was collected to measure ICAM-1, MPO, creatinine, cystatin C and lipid levels. A 24-h urine collection was obtained for assessing albumin excretion rate (AER). RESULTS: Levels of ICAM-1 and MPO were significantly higher in obese [ICAM-1: 0.606 (0.460-1.033) µg/mL; MPO: 136.6 (69.7-220.8) ng/mL] and T1D children [ICAM-1: 0.729 (0.507-0.990) µg/mL; MPO: 139.5 (51.0-321.3) ng/mL] compared with control children [ICAM-1: 0.395 (0.272-0.596) µg/mL MPO: 41.3 (39.7-106.9) ng/mL], whereas no significant difference was found between T1D and obese children. BMI z-score was significantly associated with ICAM-1 (ß = 0.21, p = 0.02) and MPO (ß = 0.41, p < 0.001). A statistically significant association was also found between ICAM-1 and markers of renal function (AER: ß = 0.21, p = 0.03; e-GFR: ß = 0.19, p = 0.04), after adjusting for BMI. CONCLUSIONS: Obese children have increased markers of endothelial dysfunction and early signs of renal damage, similarly to children with T1D, confirming obesity to be a cardiovascular risk factor as T1D. The association between ICAM-1 with e-GFR and AER confirm the known the association between general endothelial and renal dysfunction.

Compliance with enhanced recovery after surgery criteria and preoperative and postoperative counselling reduces length of hospital stay in colorectal surgery: results of a randomized controlled trial.

AIM: The aim of this randomized clinical trial was to compare patients treated using a multimodal approach [enhanced recovery after surgery (ERAS)], with a special focus on counselling, to patients treated in a standard conventional care pathway, who underwent elective colorectal resection. METHOD: In a single-centre trial, adult patients eligible for open or laparoscopic colorectal resection were randomized to an ERAS programme or standard care. The primary end-point was postoperative total hospital stay. Identical discharge criteria were defined for both treatment groups. Secondary end-points included postoperative complications, postoperative C-reactive protein levels, postoperative hospital stay, readmission rate and mortality. All parameters were recorded before operation, on the day of surgery and daily thereafter until discharge. RESULTS: Total hospital stay was significantly shorter among patients randomized to ERAS than among the standard group [median 5 days (range 2-50 days) vs median 8 days (range 2-48 days); P = 0.001]. The two treatment groups exhibited similar outcomes regarding overall major and minor morbidity, reoperation rate, readmission rate and 30-day mortality. There were also no differences in tolerance of enteral nutrition or in the inflammatory response, as reflected by postoperative C-reactive protein levels. CONCLUSION: ERAS care was associated with a significantly shorter length of hospital stay. Without any difference in surgical or general complications, tolerance of enteral nutrition or postoperative C-reactive protein levels, peri-operative information and guidance for ensuring that patients comply with the ERAS approach appear to be important factors to reduce the length of hospital stay.

Longitudinal Assessment of Blood Pressure in School-Aged Children: A 3-Year Follow-Up Study.

The purpose of this study was to assess the prevalence of abnormal blood pressure in a population of school children during a 3-year follow-up period and its relationship with obesity. Anthropometric and blood pressure data were collected from a population of Italian school children during three consecutive years. During each year blood pressure measurements were repeated three times, at intervals of 1 week. A total of 564 school-children [311 boys; mean (SD) age 8.8 ± 1.4 years] were recruited. During each year, systolic and diastolic blood pressure decreased from visit 1 to visit 3 (p < 0.001). This was associated with a decline in the percentage of prehypertension/hypertension from visit 1 to visit 3. An abnormal blood pressure value in at least one study visit was found in 8.8-17 % of children, whereas the prevalence of hypertension at all three study visits was between 5.2 and 7.8 %, and that of prehypertension at all three visits was between 2.8 and 3.8 %. High blood pressure was more frequent in obese children. In this population of school children the percentage of prehypertension/hypertension remarkably varied when based on one versus three annual assessments, thus emphasizing the importance of repeated measurement before making a diagnosis of abnormal blood pressure. Adiposity was confirmed to be a determinant of high blood pressure.

Increased left atrial size in obese children and its association with insulin resistance: a pilot study.

Subclinical cardiac abnormalities represent predisposing factors for cardiovascular disease (CVD) in obese subjects. The aim of this study was to evaluate early cardiac abnormalities in obese youth and the potential association with insulin resistance (IR). Thirty obese (12 males (M)/18 females (F); age = 11.5 ± 2.4 years; body mass index (BMI)-standard deviation score (SDS) = +2.1 ± 0.5) and 15 normal weight (10 M/5 F; age = 12.8 ± 3.1 years; BMI-SDS = +0.3 ± 0.9) children and adolescents underwent Doppler two-dimensional echocardiographic assessments of left atrial (LA) and ventricular (LV) geometry and LV diastolic function (peak early [E] and late waves, E wave deceleration time, myocardial flow velocities). Homeostasis model assessment of IR (HOMA-IR) was used as an IR index. LA size was increased in obese children, as indicated by higher LA diameter (4.9 ± 0.5 vs 4.1 ± 0.4 cm, p < 0.001), area (14.3 ± 2.5 vs 10.7 ± 2.0 cm(2), p < 0.001), and volume (33.8 ± 10.6 vs 23.7 ± 6.4 ml, p = 0.003). LV mass was also increased in obese children (87.0 ± 16.6 vs 68.8 ± 13.2 g, p = 0.003), who also showed subtle diastolic dysfunctions, as indicated by higher values of E (97.1 ± 14.3 vs 86.2 ± 11.9 cm/s, p = 0.02). All the above parameters were significantly associated with BMI-SDS (p < 0.05). In addition, HOMA-IR was independently associated with LA diameter, area, and volume (ß = 0.314, p = 0.040; ß = 0.415, p = 0.008; ß = 0.535, p = 0.001). CONCLUSION: Obese children feature increased LA size, which emerged to be mainly correlated to, and possibly driven by IR, suggesting an increased CVD risk. WHAT IS KNOWN: Left atrial and ventricular alterations have been reported in obese adults, and they represent predisposing factors for cardiovascular disease. There is some evidence suggesting that obese children show increased left ventricular mass and also increased atrial size, although with conflicting results. WHAT IS NEW: Obese normotensive children showed a moderately increased atrial size, subtle alterations in left cardiac diastolic function, and ventricular mass. An association between insulin resistance and left cardiac changes was found, although its mechanism remains to be determined.

Blood pressure from childhood to adolescence in obese youths in relation to insulin resistance and asymmetric dimethylarginine.

BACKGROUND AND PROPOSE: Hypertension is the most important cardiovascular complication of obesity, even during childhood. Several studies have demonstrated that there is a natural progression of hypertension from childhood to adulthood. However, there are no data reporting a potential worsening in blood pressure (BP) already moving from the pre-pubertal to the pubertal period in obese youths. The aim of this study was to evaluate early change in BP and its relation to insulin resistance (IR) and asymmetric dimethylarginine (ADMA). METHODS: Thirty obese children underwent a first assessment when they were pre-pubertal (visit_1) and were re-evaluated after a mean of 4.5 years (visit_2). At both visits, anthropometric parameters were assessed, blood samples were collected for measurement of insulin, glucose and ADMA and a 24-h ambulatory BP monitoring was performed. RESULTS: At visit_2, the study participants presented increased HOMA-IR and ADMA compared to visit_1 (HOMA-IR: 3.6 ± 2.8 vs 2.8 ± 1.4, p = 0.01; ADMA: 1.57 ± 0.78 vs 0.77 ± 0.52 µmol/l, p < 0.001). Values of 24-h systolic and diastolic BP SDS (0.86 ± 0.79 vs 0.42 ± 0.83, p = 0.001; -0.45 ± 0.82 vs 0.08 ± 0.51, p = 0.001) were significantly increased at visit_2 compared to visit_1. At both visits, BMI-SDS, HOMA-IR and ADMA were associated with 24-h BP. In addition, over-time changes in IR and ADMA influenced changes in systolic blood pressure and diastolic blood pressure from childhood to adolescence (p < 0.05). CONCLUSIONS: Changes in BP already occur moving from the pre-pubertal to the pubertal period in obese children, and modifications in insulin resistance and ADMA seem to be implicated in this early progression in BP.

Migraine and obesity: metabolic parameters and response to a weight loss programme.

BACKGROUND AND OBJECTIVE: Weight loss can determine significant improvement of migraine in obese patients. Herein, we evaluated a clinical sample of adolescent migraineurs with obesity who participated in an interdisciplinary programme for weight loss, in order to identify possible metabolic parameters associated with good migraine control. SUBJECTS AND METHODS: Using a cross-sectional design, we evaluated 112 out of 135 adolescents who previously underwent our intervention programme. Based on persistence of headache, subjects for comparison were 40 migraine-free and 72 not migraine-free adolescents. Participants underwent anthropometric evaluations and biochemical tests. RESULTS: Patients with persistence of migraine had significantly higher weight (P < 0.01), body mass index (P < 0.01), waist circumference (P < 0.01), homeostasis model assessment of insulin resistance (P < 0.001), triglyceride (P < 0.05), total cholesterol (P < 0.05) and low-density lipoprotein cholesterol (P < 0.05) values when compared with those who became migraine-free. Between potential predictors, only insulin resistance (odds ratio = 3.5, 95% confidence interval = 1.4-6.1; P < 0.001) was significantly associated with persistence of migraine after intervention programme. CONCLUSIONS: Among obese adolescents with migraine who underwent an intervention programme for weight loss, patients who did not become migraine-free showed higher adiposity values than those who became migraine-free. Patients with insulin resistance had 3.5 times the odds of having persistence of migraine compared with those without.

Circulating asymmetric dimethylarginine and lipid profile in pre-pubertal children with growth hormone deficiency: effect of 12-month growth hormone replacement therapy.

OBJECTIVE: Growth hormone deficiency (GHD) in adults is associated with cardiovascular complications, which lead to reduced life expectancy. At present, data on cardiovascular risk factors in GHD children are limited. The aim of this study was to evaluate whether pre-pubertal GHD children have increased cardiovascular risk factors, and whether 12-month growth hormone (GH) treatment can reverse them. DESIGN: Twenty pre-pubertal GHD children (6 boys, mean (±SD) age: 9.5±1.8 years) were matched for sex and age with 20 healthy controls (6 boys, mean (±SD) age: 8.8±1.5 years). Asymmetric dimethylarginine (ADMA), lipid profile, glucose metabolism parameters, IGF-1, blood pressure and anthropometric parameters were assessed at baseline and after 12 months of GH treatment. RESULTS: At baseline, GHD patients showed significantly higher ADMA levels (median [interquartile range]: 78.5 [69.6-123.5] vs 54.0 [38.3-60.8] ng/ml, p<0.001), total cholesterol (mean±SD: 177.5±30.4 vs 150.1±21.4 mg/dl; p=0.004) and LDL-cholesterol (mean±SD: 111.2±22.2 vs 84.9±15.9 mg/dl; p<0.001) than controls. After 12-month GH treatment, ADMA (median [interquartile range]: 55.4 [51.2-73.8] ng/ml), total cholesterol (mean±SD: 155.6±43.2 mg/dl), and LDL-cholesterol (mean±SD: 95.4±32.1 mg/dl) significantly decreased in GHD children, reaching values comparable to those in controls. CONCLUSIONS: This study showed that, as in adults, pre-pubertal GHD children manifest increased cardiovascular risk markers and that 12-month GH treatment can improve them.

Timing of puberty and physical growth in obese children: a longitudinal study in boys and girls.

OBJECTIVE: To assess whether puberty and physical growth vary in obese when compared to normal-weight children. METHODS: One hundred obese pre-pubertal children (44 boys; mean age (±SD): 9.01 ± 0.62 years; 56 girls; 8.70 ± 0.57 years) were compared to 55 normal-weight controls (27 boys; 9.17 ± 0.26 years; 28 girls; 8.71 ± 0.62 years). All study participants were followed prospectively with 6-monthly follow-up visits. At each study visit, height, weight, body mass index (BMI) and pubertal stage were assessed. RESULTS: Obese children entered puberty and achieved later stages of puberty earlier than controls (onset of puberty: boys: 11.66 ± 1.00 vs. 12.12 ± 0.91 years, P = 0.049; girls: 9.90 ± 0.78 vs. 10.32 ± 1.70, P = 0.016; late puberty: boys: 13.33 ± 0.71 vs. 14.47 ± 1.00 years, P < 0.001; girls: 11.54 ± 0.99 vs. 12.40 ± 1.02, P = 0.001). Pre-pubertal BMI standard deviation score (SDS) was inversely associated with both age at the onset of puberty (ß = -0.506, P < 0.001) and age at late puberty (ß = -0.514, P < 0.001). Obese children also showed an earlier age at peak height velocity (PHV) (boys: 12.62 ± 0.82 vs. 13.19 ± 0.96 years, P = 0.01; girls: 11.37 ± 0.89 vs. 12.77 ± 0.76, P < 0.001) and a lower PHV (boys: 7.74 ± 1.49 vs. 9.28 ± 1.64 cm year(-1) , P < 0.001; girls: 7.60 ± 1.64 vs. 8.29 ± 1.03, P = 0.03). Height SDS progressively declined over the study period in the obese group (P for trend <0.001), whereas there were no significant changes in the control group (P for trend = 0.5). CONCLUSIONS: Obese boys and girls presented an earlier onset of puberty and completion of puberty and an impaired height gain during puberty.

Influence of the Mediterranean diet on carotid intima-media thickness in hypercholesterolaemic children: a 12-month intervention study.

BACKGROUND AND AIMS: The Mediterranean diet has been recognised as having a protective role on the cardiovascular system due to its low lipid and high antioxidant content. Lipid profile and oxidant status represent two important risk factors related to endothelial dysfunction, even at early stages of cardiovascular diseases. The aim of the study was to evaluate the influence of a 12-month Mediterranean diet on the variation of lipid profile and carotid intima-media thickness (cIMT) in pre-pubertal hypercholesterolaemic children. METHODS AND RESULTS: We performed a cross-sectional study comparing lipid profile and cIMT in a group of 68 pre-pubertal children (36 with hypercholesterolaemia and 32 controls). In addition, in the hypercholesterolaemic children a 12-month intervention programme with a Mediterranean diet was started to evaluate the variation of lipid profile and cIMT. At baseline, hypercholesterolaemic children showed a significantly higher cIMT (both right and left carotid artery) compared to controls (both p < 0.05). After 12 months of diet intervention, a significant reduction of total cholesterol, LDL-cholesterol and cIMT was documented (all p < 0.05). Furthermore, at the end of follow-up, delta body mass index-Standard Deviation score and delta LDL-cholesterol were significantly and independently related to the changes of cIMT (both p < 0.05). CONCLUSION: The Mediterranean diet represents a valid approach in the treatment of hypercholesterolaemia even during childhood.

Impact of a weight loss program on migraine in obese adolescents.

BACKGROUND AND PURPOSE: Increased headache frequency and severity have been observed in obese populations, but the real impact of a weight loss treatment on headache has not been studied. We investigated this issue in a sample of obese adolescents. METHODS: In all, 135 migraineurs, aged 14-18 years, with body mass index (BMI) ≥ 97 th percentile, participating in a 12-month-long program, were studied before and after treatment. The program included dietary education, specific physical training, and behavioral treatment. RESULTS: Decreases in weight (P < 0.01), BMI (P < 0.01), waist circumference (P < 0.01), headache frequency (P < 0.01) and intensity (P < 0.01), use of acute medications (P < 0.05), and disability (P < 0.05) were observed at the end of the first 6-month period and were maintained through the second 6 months. Both lower baseline BMI and excess change in BMI were significantly associated with better migraine outcomes 12 months after the intervention program. CONCLUSIONS: Significant improvements in both adiposity and headache data were observed in obese adolescents with migraine who participated in a 12-month-long interdisciplinary intervention program for weight loss. Initial body weight and amount of weight loss may be useful for clinicians to predict migraine outcomes.

Relationship between inflammatory markers, oxidant-antioxidant status and intima-media thickness in prepubertal children with juvenile idiopathic arthritis.

OBJECTIVE: To investigate the presence of possible early atherosclerotic changes in a group of prepubertal children with juvenile idiopathic arthritis (JIA) and to establish the potential beneficial effects of 1-year treatment. MATERIALS AND METHODS: Inflammatory markers (C-reactive protein, erythrocyte sedimentation rate), proinflammatory cytokines (IL-1ß, IL-6, IFN-γ, TNF-α), lipid profile and oxidant-antioxidant status (urinary isoprostanes [PGF-2α]) were assessed in 38 JIA children (12M/26F, mean age 7.05 ± 2.39 years) and compared with 40 controls (18M/22F, mean age 6.34 ± 2.25 years). Carotid intima-media wall thickness (cIMT) was obtained and blood pressure was measured. All parameters were reassessed in JIA children after 1 year of therapy. RESULTS: At baseline JIA children presented compared to controls higher levels of inflammatory markers, proinflammatory cytokines, total cholesterol, LDL cholesterol, and PGF-2α (all p ≤ 0.01). Furthermore, blood pressure and cIMT were significantly increased (both p ≤ 0.01). After a 1-year treatment with non-steroid anti-inflammatory (NSAIDs) and disease-modifying antirheumatic drugs (DMARDs), a significant reduction of all parameters was detected (all p ≤ 0.01). This was associated with a significant reduction in blood pressure and cIMT (both p ≤ 0.01). Within the JIA group, patients requiring etanercept presented worse laboratory values and cIMT measurements at baseline. Nevertheless, the same improvement of all parameters was obtained after a 1-year treatment. In stepwise multiple regression, LDL cholesterol and IL-1ß were mainly related to cIMT. CONCLUSION: Chronic and systemic inflammation seems to lead to early atherosclerotic abnormalities even in pre-pubertal JIA children. Substantial improvement can be obtained with 1-year of appropriate therapy.

Improved oxidative stress and cardio-metabolic status in obese prepubertal children with liver steatosis treated with lifestyle combined with Vitamin E.

In obese adults with non alcoholic fatty liver disease (NAFLD), treatment with Vitamin E has resulted in an improvement in liver histology, whereas variable and limited results are available in children. Our aim was to assess whether lifestyle combined with supplementation with Vitamin E might reduce oxidative stress and improve cardio-metabolic status in obese children with NAFLD. 24 obese prepubertal children (16M) followed a 6-month lifestyle intervention combined with Vitamin E supplementation (600 mg/day) and they were compared with 21 age and sex-matched obese peers who underwent lifestyle intervention only. At baseline and after 6-month urinary prostaglandin F2α (PGF-2α), endogenous secretory receptor for advanced glycation end products (esRAGE), high sensitivity C-reactive protein (hs-CRP), alanine aminotransferases (ALT), lipid profile, glucose, and insulin were assessed. The two groups were comparable for age (8.3 ± 1.6 vs 8.4 ± 1.3 yr), sex and BMI SDS (2.16 ± 0.29 vs 2.13 ± 0.28). At the beginning of the study, PGF2-α, esRAGE hsCRP, ALT, lipid profile and HOMA-IR levels were similar between the two groups (all p > 0.05). After 6-month treatment, levels of PGF2-α (p < 0.001) significantly decreased and esRAGE significantly increased (p < 0.001) in children treated with Vitamin E. A significant reduction was also found in ALT (p = 0.001), lipid profile and HOMA-IR (p < 0.001). In contrast, no significant change in any of these markers was detected in the lifestyle only group. In conclusion, Vitamin E supplementation was associated with a significant reduction in oxidative stress and improved cardio-metabolic alterations. These data suggest that Vitamin E supplementation could represent a valuable treatment in obese children affected by NAFLD.

Delayed Diagnosis of Potocki-Shaffer Syndrome in a Woman with Multiple Exostoses and Mental Retardation.

We describe the case of an adult patient affected by multiple exostoses, severe mental retardation, epilepsy and facial dysmorphisms with a deletion of ∼2.3 Mb on chromosome 11p11.21, correlated to Potocki-Shaffer syndrome (PSS). PSS is a rare contiguous gene deletion syndrome, mainly characterized by multiple exostoses and bilateral parietal foramina. Mental retardation and craniofacial dysmorphisms have often been reported, too. Although the patient showed many signs of PSS since early childhood, the diagnosis was suggested only when we examined her at adult age. This case highlights how frequently rare diseases remain undiagnosed till adulthood and is an excellent example of the need for a timely and correct diagnosis.

Role of ultrasonography in the diagnosis and follow-up of pediatric eosinophilic gastroenteritis: a case report and review of the literature.

Eosinophilic gastroenteritis (EG) is a rare disease characterized by the infiltration of one or more layers of the digestive tract by eosinophilic leukocytes. The diagnosis is confirmed by histological examination of a characteristic biopsy, but radiological features are useful for diagnostic suspicion. We report the case of an adolescent boy with recurrent epigastric pain, nausea and vomiting, in whom sonographic features and eosinophilia of the peripheral blood suggested the diagnosis of EG. Moreover, we reviewed the radiological features of EG with particular regard to the role of sonography in the diagnosis and follow-up of EG, especially in children. We emphasize the utility of sonography in pediatric patients presenting with gastrointestinal symptoms, since it may provide useful information in a quick, inexpensive and noninvasive way. Ultrasonographic detection of features such as bowel wall thickness, ascites and peritoneal nodules may be largely suggestive of EG and may prevent other invasive exams and abdominal surgery. Ultrasonography can also be easily used in the follow-up of these patients, and may obviate the frequent and potentially dangerous exposure to radiation.

An insulin-like growth factor-I receptor defect associated with short stature and impaired carbohydrate homeostasis in an Italian pedigree.

BACKGROUND: Mutations in the insulin-like growth factor-I (IGF-I) receptor (IGF1R) have been associated with prenatal and postnatal growth retardation. However, little is known about potential effects of mutations in the IGF1R on carbohydrate homeostasis. METHODS: We investigated clinical, endocrine and metabolic parameters in four family members carrying a novel IGF1R mutation (p.Tyr387X): an 18-year-old male (index case), his sister and two paternal aunts. RESULTS: All family members showed a variable degree of impairment in prenatal growth, with birth weight standard deviation scores (SDS) between -1.65 and -2.37 and birth length SDS between -1.78 and -3.08. Their postnatal growth was also impaired, with height SDS between -1.75 and -4.86. The index case presented high IGF-I levels during childhood and adolescence and delayed bone age. The index case and his two paternal aunts had impaired glucose tolerance (IGT) associated with a variable degree of alterations in insulin sensitivity and secretion. In contrast, the index case's sister, who had had IGT during pregnancy, showed normal glucose metabolism but reduced insulin sensitivity. CONCLUSION: This is the first study showing an association between a novel IGF1R mutation and a variable degree of alterations in prenatal and postnatal growth and in carbohydrate metabolism.

Macrovascular angiopathy in children and adolescents with type 1 diabetes.

Diabetes represents one of the most common diseases globally. Worryingly, the worldwide incidence of type 1 diabetes (T1D) is rising by 3% per year. Despite the rapid increase in diabetes incidence, recent advances in diabetes treatment have been successful in decreasing morbidity and mortality from diabetes-related retinopathy, nephropathy, and neuropathy. In contrast, there is clear evidence for the lack of improvement in mortality for cardiovascular diseases (CVDs). This emphasizes the importance of focusing childhood diabetes care strategies for the prevention of CVD in adulthood. Furthermore, although most work on diabetes and macrovascular disease relates to type 2 diabetes, it has been shown that the age-adjusted relative risk of CVD in T1D far exceeds that in type 2 diabetes. As T1D appears predominantly during childhood, those with T1D are at greater risk for coronary events early in life and require lifelong medical attention. Because of the important health effects of CVDs in children and adolescents with T1D, patients, family members, and care providers should understand the interaction of T1D and cardiovascular risk. In addition, optimal cardiac care for the patient with diabetes should focus on aggressive management of traditional cardiovascular risk factors to optimize those well-recognized as well as new specific risk factors which are becoming available. Therefore, a complete characterization of the molecular mechanisms involved in the development and progression of macrovascular angiopathy is needed. Furthermore, as vascular abnormalities begin as early as in childhood, potentially modifiable risk factors should be identified at an early stage of vascular disease development.