Severe pediatric obesity: Diagnostic aspects

Severe pediatric obesity is a complex, chronic endocrine disease caused by genetic, environmental, behavioral, socioeconomic and cultural factors. In a minority of children with severe obesity, the obesity phenotype is caused by a singular underlying medical cause interfering with the function of the brain areas that regulate satiety and energy expenditure. Current guidelines define the following underlying medical causes: (1) genetic obesity disorders, (2) hypothalamic obesity, (3) endocrine obesity, and (4) medication-induced obesity. This thesis investigated several important diagnostic aspects of severe pediatric obesity. For example, the yield of the systematic diagnostic workup of Obesity Center CGG is described. A singular underlying medical cause was identified in 19% of patients, most of which (13%) were genetic obesity disorders (13% of patients). This shows that an extensive diagnostic approach is needed to identify the underlying medical causes. Furthermore, this thesis shows that the reported prevalence of a specific genetic obesity disorder, leptin receptor deficiency deficiency in Europe is only 2% of predicted prevalence, suggesting underreporting, underdiagnosis, early mortality, or a combination of these factors. This suggests that genetic screening should be performed in all cases with early-onset severe obesity and hyperphagia. This thesis also describes BMI trajectories of patients with genetic obesity and controls with obesity from a population-based cohort study. The presented BMI trajectories can thereby guide clinicians’ decision to perform genetic testing. Finally, a general discussion in the context of current literature is provided, including recommendations, future perspectives and implications.