Large-scale screening of lipase acid deficiency in at risk population.

BACKGROUND: Lysosomal acid lipase deficiency (LALD, OMIM#278000) is a rare lysosomal disorder with an autosomal recessive inheritance. The main clinical manifestations are related to a progressive accumulation of cholesteryl esters, triglycerides or both within the lysosome in different organs such as the liver, spleen, and cardiovascular system. A wide range of clinical severity is associated with LALD including a severe very rare antenatal/neonatal/infantile phenotype named Wolman disease and a late-onset form named cholesteryl ester storage disease (CESD). METHODS: This study aimed to investigate a cohort of at-risk patients (4174) presenting with clinical or biological signs consistent with LALD using the assessment of LAL activity on dried blood spots. RESULTS: LAL activity was lower than 0.05 nmol/punch/L (cut-off: 0.12) in 19 patients including 13 CESD and 6 Wolman. Molecular study has been conducted in 17 patients and succeeded in identifying 34 mutated alleles. Fourteen unique variants have been characterized, 7 of which are novel. CONCLUSION: This study allowed to identify a series of patients and expanded the molecular spectrum knowledge of LALD. Besides, a new screening criteria grid based on the clinical/biological data from our study and the literature has been proposed in order to enhance the diagnosis rate in at risk populations.

Long-Term Results of Laparoscopic Adjustable Gastric Banding in French adolescents: The Utmost Importance of Follow-Up.

OBJECTIVES: To investigate the long-term follow-up (FU) and effectivity of laparoscopic adjustable gastric banding (LAGB) in a French adolescent cohort. METHODS: We retrospectively analyzed the results of LAGB at our institution. We collected information on FU, adjustable gastric banding (AGB) status, weight-related parameters, and comorbidity at multiple timepoints. RESULTS: Fifty-six patients (77% female) with a mean age of 16.5 years and a mean body mass index (BMI) of 45 kg/m2 underwent LAGB over a period of 12 years. The mean postpediatric FU was 23 months. FU decreased progressively from 96% at 3 years to 54% and 29% at 6 and 9 years, respectively. The loss to FU was 39% at last contact. AGB was removed in 17 patients (30%) and 12 patients (21%) underwent a second bariatric procedure. Mean BMI decreased by 11 kg/m2 at last contact (P < 0.001). The prevalence of most comorbidities also decreased significantly after 3 years. The mean excess weight loss (to reach a BMI of 25 kg/m2) was 47% during the first year postsurgery and further increased to 55% at last contact. CONCLUSION: Overall, AGB resulted in significant weight loss; however, the increase in heterogeneity suggests that LAGB is more effective in some individuals than in others in the long-term. This study confirmed that LAGB is a valuable bariatric procedure in adolescents, either as a long term-term efficient or bridging method that would be replaced at the time of transition to adult care. The importance of a standardized long-term follow-up should always be emphasized.

Prenatal education of overweight or obese pregnant women to prevent childhood overweight (the ETOIG study): an open-label, randomized controlled trial.

BACKGROUND: We aimed to evaluate whether pre and perinatal education of pregnant women would reduce childhood overweight. METHODS: Four French centers included women at ≤21 gestational weeks (GWs) with body mass index (BMI) >25 kg/m2 before pregnancy. Patients were randomized to a control group (routine care including at least one dietary visit) or an intervention group (2 individuals (26 and 30 GW) and 4 group sessions (21, 28, 35 GW, 2 months postpartum)) aimed at educating the future mother regarding infant and maternal nutrition. The primary objective was to reduce post-natal excessive weight gain in the infant from birth to 2 years (NCT00804765). This project was funded by a grant from the National Programme for Hospital Research (PHRC-2007 French Ministry of Health). RESULTS: We included 275 women (BMI: 32.5 kg/m2). The rate of post-natal excessive weight gain was similar in the intervention (n = 132) and control (n = 136) groups by intention to treat (ITT: 59.1% vs 60.3% respectively, p = 0.84) in available data (AD, n = 206) and by per-protocol analysis (PP, n = 177). Two years after delivery, normalization of maternal BMI and number of infants with BMI < 19 kg/m2 were not significantly different in the interventional group in ITT and in the control group. Although not significantly different in ITT, normalization of maternal BMI was more frequent in AD (n = 149: 12.9% vs 3.8%, p = 0.04) and 2-year-old infant BMIs were less likely to be >19 kg/m2 in the intervention group in AD (n = 204: 0% vs 6.8%, p = 0.014) and PP (n = 176: 0% vs 6.4%, p = 0.03). CONCLUSIONS: An education and nutritional counseling program for overweight women, starting after 3 months of gestation, did not significantly change post-natal excessive weight gain of infants or prevent overweight in mothers and children 2 years after delivery.

European paediatric non-alcoholic fatty liver disease registry (EU-PNAFLD): Design and rationale.

Non-alcoholic fatty liver disease (NAFLD) is the most common liver disorder in children and has the potential to progress to advanced fibrosis/cirrhosis, end-stage liver disease and hepatocellular carcinoma. However, the natural history of the condition is poorly understood and there are no approved treatments. The European Paediatric Non-Alcoholic Fatty Liver Disease Registry (EU-PNAFLD) is a multi-centre registry of paediatric NAFLD that will serve as a prospective, observational, natural history study and provide a tractable back-bone to support recruitment into subsequent interventional trials. Collection of samples into a bio-repository will facilitate translational studies, including genome sequencing and metabolomics. EU-PNAFLD will work closely alongside the existing adult European NAFLD Registry to obtain data on clinical outcomes after 20-30 years. Through an international, well-characterised large-scale cohort, EU-PNAFLD will address the key questions in paediatric NAFLD and benefit patients with the condition.

Comparative results of gastric banding in adolescents and young adults.

BACKGROUND/PURPOSE: Obesity has become a major public health priority. Because of disappointing results obtained with dietary and medical programs, bariatric surgery has been offered to adolescents, although this practice remains controversial. Our aim was to evaluate laparoscopic adjustable gastric banding (LAGB) in adolescents at 2-year follow-up. MATERIAL AND METHODS: This prospective study, from 2008 to 2013, compared results between adolescent patients and young adult controls. The LAGB technique and the follow-up program were similar. Weight loss and comorbid disease were analyzed. RESULTS: Thirty-six adolescents (mean age at surgery=16.7±1.3years) were operated on and compared to 53 young adults (mean age at surgery=21.7±1.9years). The mean weight and BMI at surgery were 124.4±20.7 and 43.9±5.5kg/m(2), respectively. Among the adolescents, none were diabetic or hypertensive. The mean glycated hemoglobin was 5.6±1.2%. In four cases (11%) dyslipidemia was observed. There was no significant difference between the two groups in terms of initial preoperative weight or BMI. The absolute BMI values at 6, 12 and 24months after surgery were comparable between adolescents and young adults: 38.7 vs 39.8, 36.0 vs 37.6 and 33.5 vs 36.1kg/m(2), respectively. The excess weight loss was higher in adolescents at 12 and 24months: 48.6 vs 37.6% (p=0.03); and 62.3 vs 45.5% (p=0.02). During this period, insulin resistance and dyslipidemia decreased similarly in both groups. CONCLUSION: Provided there is careful selection of patients and a supportive multidisciplinary team, satisfying results can be obtained after LAGB in adolescents, comparable to those obtained in young adults at 2-year follow-up.

Primordial Influence of Post-operative Compliance on Weight Loss After Adolescent Laparoscopic Adjustable Gastric Banding.

BACKGROUND: Accumulating evidence suggests that the benefits seen in adult bariatric surgery can be reproduced in adolescents. In contrast with North America, bariatric surgery in adolescents is still not well accepted in Europe and indications and protocols have still to be formulated. METHODS: This prospective study tested the gastric banding procedure in 49 patients operated in a single French institution since 2008. The mean age at surgery was 16.2 ± 0.9 years with a weight of 118.8 ± 22.3 kg and body mass index of 42.5 ± 5.9 kg/m(2). RESULTS: At 6, 12 and 24 months after surgery, weight was 103.7 ± 20.8 kg, 98.7 ± 21 kg and 93.6 ± 19.3 kg, respectively (p < 0.001), corresponding to excess weight loss (EWL) of 31.6 ± 17.2 %, 41.8 ± 21.4 % and 59.1 ± 24.9 % (p < 0.001), respectively. Multivariate analysis showed that the number of consultations per year was the only variable significantly associated to weight loss. Metabolic disorders were corrected, with a decreased prevalence of insulin resistance from 100 to 17 % and normalisation of homeostasis model assessment-insulin resistance (HOMA-IR) at 24 months (2.09 ± 0.95). Band-related complications were five slippages, one psychological intolerance and two ports repositioning. Six patients (12 %) had the device explanted. The death of a patient was an exceptionally severe adverse event. CONCLUSION: Given frequent follow-up support by a multidisciplinary team, laparoscopic adjustable gastric banding (LAGB) surgery in adolescent results in sustained weight loss. However, even exceptional, potentially serious complications are possible and long-term follow-up is needed to evaluate the risk/benefit ratio at 5 or 10 years after LAGB surgery.

High prevalence of hirsutism and menstrual disorders in obese adolescent girls and adolescent girls with type 1 diabetes mellitus despite different hormonal profiles.

OBJECTIVES: To compare the pubertal development, the hormonal profiles and the prevalence of hirsutism and menstrual disorders in obese adolescent girls and adolescent girls with type 1 diabetes mellitus (T1DM). METHODS: Data were collected from 96 obese adolescent girls and 78 adolescent girls with T1DM at Tanner stage IV or V, whose ages ranged between 11.9 and 17.9 years. RESULTS: High prevalence of hirsutism and menstrual disorder was found in the obese adolescent girls (36.5 and 42% respectively) and the adolescent girls with T1DM (21 and 44% respectively). The obese girls were significantly younger at pubarche, thelarche and menarche than the girls with T1DM. Hirsutism in the obese girls and those with T1DM was associated with hyperandrogenaemia and a raised free androgen index (FAI). When the cause of the raised FAI was investigated in both the groups of girls with hirsutism, the raised FAI in the obese girls was due to low serum sex hormone-binding globulin (SHBG) levels. In contrast, the raised FAI of the girls with T1DM and hirsutism was due to hyperandrogenaemia. Menstrual disorders in the T1DM girls were associated also with hyperandrogenaemia unlike obese girls. CONCLUSIONS: Hirsutism and menstrual disorders are common in obese adolescent girls and adolescent girls with T1DM. Although hyperandrogenaemia is present in both groups of girls, the androgenic profiles of the two groups differ. The hyperandrogenaemia in the obese girls is primarily due to their decreased serum SHBG levels, whereas the hyperandrogenaemia in the girls with T1DM is due to their increased androgen production.

Evaluation of lean body mass in obese children.

UNLABELLED: Multiple skinfold anthropometry (MSA) and bioelectrical impedance analysis (BIA) are useful as clinically non-invasive, inexpensive and portable techniques, although it is not clear if they can be used interchangeably in the same patient to routinely assess her/his body composition. In order to compare BIA, MSA and DXA in the estimation of lean body mass (LBM) of a pediatric obese population, 103 obese [body mass index (BMI) > 97th percentile] children (median age: 11 years; range: 5.4-16.7 years) underwent nutritional evaluation. After an overnight fast, the subjects' anthropometric measurements were performed by the same investigator: body weight (BW), height, skinfold thickness (four sites); fat body mass (FBM) using Brook or Durnin equations and dual X-ray absorptiometry (DXA). BIA was performed using a bioelectrical impedance analyzer (Analicor-Eugedia, 50 kHz) and Houtkooper's equation to calculate LBM. Linear regression analysis was performed to evaluate the relationship between the prediction of LBM by MSA, DXA and BIA. The differences between the three techniques were analysed using Student's t-test for paired observations and the Bland and Altmann method. A considerable lack of agreement was observed between DXA- and BIA-LBM (delta = -4.37 kg LBM; delta-2sigma = -11.6 kg LBM; delta+2sigma = +2.8 kg LBM); between DXA- and MSA-LBM (delta = -1.72 kg LBM; delta-2sigma = -8.2 kg LBM; delta+2sigma = +4.8 kg LBM) and between BIA- and MSA-LBM (delta = -2.65 kg LBM; delta-2sigma = -10.5 kg LBM; delta+2sigma = +5.2 kg LBM). CONCLUSION: In obese children, DXA, BIA and MSA should not be used interchangeably in the assessment of LBM because of an unacceptable lack of agreement between them. The discrepancies between methods increase with the degree of obesity.

Insulin resistance and the metabolic syndrome in obese French children.

OBJECTIVE: To estimate the frequency of the metabolic syndrome (MS) and of the insulin resistance syndrome (IRS) in overweight or obese French children and to determine the risk factors. DESIGN, PATIENTS AND METHODS: A total of 308 overweight and obese children [166 girls, 142 boys, aged 7-17 years; median body mass index (BMI) 4.7 standard deviation (SD) (Q1-Q3: 3.9-5.8) adjusted for age and sex] were included. The frequency of the MS was assessed with the National Cholesterol Education Program (NCEP) Adult Treatment Panel III (ATP III) criteria and the frequency of the IRS with World Health Organization (WHO) criteria. RESULTS: The overall frequency of MS and IRS was 15.9% and 42.5%, respectively. The most common component, after abdominal obesity (95.8%) and IR (71.8%), was elevated systolic blood pressure (28.6%). The frequency of glucose tolerance disorders was low (3.6%). The frequency of MS was independently influenced by homeostatic model assessment (HOMA) (P = 0.06) and waist-to-hip ratio (P = 0.09), whereas the frequency of IRS was influenced by adiposity (degree of obesity: P = 0.02; waist-to-hip ratio: P = 0.05), puberty (P = 0.05) and mother's BMI (P = 0.01). Ethnicity had no effect on either MS or IRS. CONCLUSIONS: Metabolic complications and IR are frequent in overweight and obese children whereas the frequency of glucose tolerance disorders is very low. IRS is more prevalent than MS, indicating a major role of IR, which could precede the other metabolic complications in obese children. IRS is a relevant marker for the risk of type 2 diabetes (T2D) and cardiovascular complications in obese European children.

Mental disorders in obese children and adolescents.

OBJECTIVE: To evaluate the type and frequency of psychiatric disorders in obese children and adolescents; to assess the correlation between psychopathology and severity of obesity; to explore the relationship between psychiatric disorders in obese children and obesity and psychopathology in their parents. METHODS: One hundred fifty-five children referred and followed for obesity were evaluated (98 girls and 57 boys; age, 5 to 17 years). Psychiatric disorders were assessed through a standardized diagnostic interview schedule (K-SADS R) and self-report questionnaires completed by the child (STAIC Trait-anxiety and CDI for depression) or his (her) parents (CBCL or GHQ). These obese children were compared with insulin-dependent diabetic (IDDM) outpatient children (N = 171) on questionnaire data. RESULTS: Eighty-eight obese children obtained a DSM-IV diagnosis, most often an anxiety disorder (N = 63). Psychological disorders were particularly pronounced in those obese children whose parents were disturbed. There was no correlation between severity of obesity in the child or his (her) parents and frequency of psychiatric disorders. Compared with diabetic children, they displayed significantly higher internalized and externalized questionnaire scores and poorer social skills. CONCLUSION: These results highlight the importance of including a child psychiatric component in the treatment of obesity, which must engage the whole family.