OR14-2 Age of Onset of Obesity and Childhood BMI Trajectories in Rare Genetic Obesity Disorders

INTRODUCTION: Early-onset obesity is a cardinal feature of rare genetic obesity disorders. According to the Endocrine Society guideline, genetic screening is indicated in selected cases with age of onset (AoO) of severe obesity (grade ≥2) <5 years. However, this cut-off is not validated. AIMS: To present the detailed BMI characteristics of children and adolescents with rare genetic obesity disorders; to evaluate whether the following growth chart characteristics can aid in assessing which children should be screened for genetic obesity disorders: AoO of obesity, AoO of severe obesity, BMI standard deviation scores (SDS) at yearly age intervals. METHODS: In this prospective observational study, children with non-syndromic and syndromic genetic obesity disorders treated at our tertiary obesity center were included. Growth measurements from birth onwards were collected. Children with obesity from a population-based cohort study with follow-up until age 10 years were included as an unselected reference cohort. Diagnostic performance (sensitivity [sens], specificity [spec], positive likelihood ratio [LR+], area-under-the-curve [AUC]) for AoO of obesity and severe obesity and for BMI-SDS at yearly age intervals was calculated. RESULTS: We included 64 children with genetic obesity disorders (32 non-syndromic, 32 syndromic) and 298 control children with obesity. At intake, median age of children with genetic obesity was 10.5 years (IQR 7.0–14.7) and mean BMI-SDS +3.1 ± 1.1. Median AoO of obesity was 1.2 years (IQR 0.6–3.7) in non-syndromic genetic obesity, 2.1 years (IQR 0.9–4.2) in syndromic genetic obesity, and 3.8 years (IQR 2.3–6.2) in the control population. For non-syndromic genetic obesity, optimal cut-off value for AoO of obesity was ≤1.5 years: sens 0.60, spec 0.88, LR+ 5.22, AUC 0.79 (p<0.001). For syndromic genetic obesity, optimal cut-off was ≤3.0 years: sens 0.68, spec 0.68, LR+ 2.06, AUC 0.67 (p=0.001). AoO of severe obesity showed worse diagnostic performance than AoO of obesity in both non-syndromic (AUC 0.58, p=0.20) and syndromic genetic obesity (AUC 0.58, p=0.21). Moreover, when the guideline cut-off <5 years was used, AoO of severe obesity showed a negative diagnostic performance (non-syndromic genetic obesity: sens 0.76, spec 0.13, LR+ 0.88; syndromic genetic obesity: sens 0.85, spec 0.14, LR+ 0.98). BMI-SDS showed good diagnostic performance for non-syndromic genetic obesity across the age intervals (AUCs 0.79-0.89, all P<0.001) but not for syndromic genetic obesity (AUCs 0.54-0.71, P-values ranging from <0.001-0.50). CONCLUSION: This study shows that growth charts characteristics such as BMI-SDS and AoO of obesity (grade 1), but not AoO of severe obesity (grade ≥2), could be useful to distinguish between children with genetic obesity disorders and children with obesity from a population-based cohort study. However, all investigated growth charts characteristics showed misclassification, especially in syndromic genetic obesity, indicating that additional clinical features should be present to warrant genetic testing in these children. Presentation: Sunday, June 12, 2022 11:15 a.m. - 11:30 a.m.