How early is ‘extreme early-onset obesity’? Results of comprehensive growth curve analysis to identify genetic obesity disorders based on age of onset of obesity - Nederlandse Vereniging voor Endocrinologie

Background: Early-onset obesity is associated with genetic obesity. According to the Endocrine Society guideline, genetic screening is indicated in selected cases with age of onset (AoO) <5y. However, this lacks evidence. Identifying genetic obesity is vital as treatment for some disorders is available. We investigated the predictive value of AoO for genetic obesity and its optimal cut-off.

Methods: In this study, patients visiting a specialized pediatric obesity center were included and underwent genetic testing (obesity gene panel, SNP array). Genetic obesity disorders were grouped based on presence of intellectual disability (ID). We compared AoO in genetic obesity to AoO in patients with lifestyle-induced obesity, i.e., patients without a somatic diagnosis (no genetic, endocrine, cerebral or medication-induced obesities) in whom lifestyle factors played the main role. AoO of obesity was assessed using patients’ growth charts. Obesity was defined <2y as weight-for-height >+3SDS for WHO median, and >2y as BMI-for-age >+2.3SDS. Performance of AoO and optimal cut-off were determined.

Results: In total, 84 patients were included: 34 with genetic obesity (16 with ID; 18 without), 50 with lifestyle-induced obesity. Median age at intake was 11.6y (IQR 7.8–14.8); mean BMI +3.8SDS (SD 1.2). Median AoO was 0.7y (IQR 0.4–1.1) in genetic obesity without ID, 2.4y (IQR 1.2–6.2) in genetic obesity with ID and 3.1y (IQR 1.8–4.7) in lifestyle-induced obesity. AoO ≤1y was the optimal cut-off (sens 53%, spec 96%, LR+ 13.2) compared to <5y (sens 82%, spec 22%, LR+ 1.1). AoO performed well in genetic obesity without ID (AUC 0.90, p<0.001), but not in genetic obesity with ID (AUC 0.56, p=0.74).

Conclusion: Age of onset of obesity, with optimal cut-off ≤1y, is useful to identify which children without ID should undergo genetic screening and performs better than the guideline cut-off <5y. However, AoO of obesity was not discriminative in genetic obesity with ID compared to children with lifestyle-induced obesity in a specialized pediatric obesity center.