S. Di Candia

Metabolic syndrome in children with Prader–Willi syndrome: The effect of obesity

BACKGROUND AND AIMS Prader-Willi syndrome (PWS), the most frequent syndromic obesity, is associated with elevated morbidity and mortality in pediatric and adult ages. In PWS, the presence of metabolic syndrome (MS) has not yet been established. The aim of the study was to estimate the frequency of MS and its components in pediatric subjects according to obesity status. METHODS AND RESULTS A cross-sectional study was performed in 109 PWS children aged 2-18 years (50 obese and 59 non-obese) and in 96 simple obese controls matched for age, gender, and also for BMI with obese PWS. Obesity was defined when SDS-BMI was >2. Non-obese PWS showed significantly lower frequency of hypertension (12%) than obese PWS (32%) and obese controls (35%)(p=0.003). The same was observed for low HDL-cholesterol (3% vs 18% and 24%, p=0.001) and high triglycerides (7% vs 23% and 16%, p=0.026). Frequency of altered glucose metabolism was not different among groups (2% vs 10% and 5%), but type 2 diabetes (four cases) was present only in obese PWS. Non-obese PWS showed lower insulin and HOMA-index respect to obese PWS and obese controls (p ≤ 0.017). Overall MS frequency in PWS was 7.3%. None of the non-obese PWS showed MS compared with 16% of obese PWS and controls (p<0.001). When obesity was excluded from the analysis, a significantly lower frequency for clustering of ≥ 2 factors was still found in non-obese PWS (p=0.035). CONCLUSION Non-obese PWS showed low frequency of MS and its components, while that observed in obese PWS was very close to those of obese controls, suggesting the crucial role of obesity status. Prevention of obesity onset remains the most important goal of PWS treatment. Early identification of MS could be helpful to improve morbidity and mortality in such patients.

Metabolic syndrome in adult patients with Prader-Willi syndrome

BACKGROUND AND AIMS Prader-Willi syndrome (PWS), the most common genetic cause of obesity, is characterized by elevated morbility and mortality in all ages. In this context, non-obese PWS children showed low frequency of metabolic syndrome (MetS), while a comparable prevalence was observed in obese PWS and obese controls. Aim of this study was to estimate the occurrence of MetS and its components in a large group of PWS adults, according to obesity status. METHODS AND RESULTS A cross-sectional study was performed in 108 PWS aged 18.0-43.2 years (87 obese and 21 non-obese) and in 85 controls with nonsyndromic obesity matched for age, gender, and BMI with obese PWS. Non-obese PWS showed lower waist circumference, insulin, HOMA-index, triglycerides, diastolic blood pressure, and higher HDL-C than both obese PWS and obese controls (p < 0.017). Obese PWS showed higher glucose and systolic blood pressure than both non-obese PWS and obese controls (p < 0.017). MetS was found in 1/21 (4.8%) non-obese PWS, 36/87 (41.4%) obese PWS and 39/85 (45.9%) obese controls. Non-obese PWS showed lower frequency for each MetS component as compared with obese PWS and obese controls. PWS patients with deletion of the chromosome 15q11-13 showed a lower risk for low HDL-C (p < 0.01) and a trend towards a lower MetS risk (p < 0.06) compared to subjects without deletion. CONCLUSION Our findings suggest the main role that obesity status plays on the individual metabolic risk clustering in PWS adults. Early identification of MetS could be helpful to improve morbidity and prevent mortality in such patients.

POI: A Score to Modulate GH Treatment in Children with Prader-Willi Syndrome

a Paediatric Endocrinology Unit, Insubria University, Varese , b Paediatric Department, Università Vita e Salute, San Raffaele Hospital, Milan , c Unit of Autoimmune Endocrine Diseases, Bambino Gesù Children’s Hospital, Research Institute, Palidoro-Rome , d Department of Paediatrics, Civic Hospital, Treviglio , e Department of Auxology, S. Giuseppe Hospital, Research Institute, Italian Auxological Institute Foundation, Verbania , f Paediatric Clinic, University of Modena e Reggio Emilia, Modena e Reggio Emilia , and g Paediatric Unit, Hospital of Rho, Rho , Italy

Screening for mutations in the ISL1 gene in patients with thyroid dysgenesis.

Context: Congenital hypothyroidism (CH) is a common endocrine disorder with an incidence of 1:3000–4000 newborns. In 80–85% of cases, CH is caused by defects in thyroid organogenesis, resulting in absent, ectopically located, and/or severely reduced gland, all conditions indicated as “thyroid dysgenesis” (TD). A higher prevalence of congenital heart diseases has been documented in children with CH compared to the general population. This association suggests a possible pathogenic role of genes involved in both heart and thyroid development. Among these, it can be included Isl1, a transcription factor containing a LIM homeodomain that is expressed in both thyroid and heart during morphogenesis. Objective: In the present study, we investigate the role of ISL1 in the pathogenesis of TD. Settings and patients: By single stranded conformational polymorphism, we screened for mutations the entire ISL1 coding sequence in 96 patients with TD and in 96 normal controls. Results: No mutations have been found in patients and controls. Conclusion: Our data indicate that, despite the relevant role of ISL1 in thyroid and heart morphogenesis, mutations in its coding region are not associated with TD in our group of patients.