P-246: BMI variation in patients with Bardet Biedl and Alstrom syndrome treated with setmelanotide at pedro de Elizalde’s children hospital. Buenos Aires, Argentina

Introduction

Impaired ciliary signaling in the melanocortin-4 receptor (MC4R) pathway may contribute to obesity in patients with Bardet-Biedl syndrome (BBS) and Alström syndrome, rare genetic disorders associated with hyperphagia and early-onset severe obesity. Recently, an agonist of the Melanocortin 4 Receptor (MC4R), Setmelanotide, was approved for long-term weight control in syndromes affecting this pathway from 2 years old, revealing improvements in hunger and eating behavior, resulting in weight loss

Objectives

To describe BMI variation in patients with BBS and Alström syndrome treated with setmelanotide at the Nutrition Unit of Elizalde Children’s Hospital, Buenos Aires

Methods

Patients ≥2 years with a clinical diagnosis of BBS (Beales criteria) or Alström syndrome (Marshall criteria) and at least one related genetic variant were included. Five patients received 12 weeks of setmelanotide. In patients <12 years, the starting dose was 0.5 mg with titration up to 2.5 mg/day; in those ≥12 years, 1 mg up to 3 mg/day. Patients exhibiting favorable clinical outcomes and acceptable tolerability remained on treatment.

Results

Conclusions

Bardet-Biedl (BBS) and Alström syndromes are characterized by hyperphagia, which frequently leads to the development of severe obesity. This study represents the first pivotal clinical trial in Argentina to evaluate a melanocortin-4 receptor (MC4R) agonist for these conditions. Given the low prevalence of these rare diseases, a non-traditional trial design was utilized. All participants demonstrated clinical tolerability, maintaining treatment beyond the 12-week mark. The most prevalent adverse events were cutaneous hyperpigmentation (100%) and injection-site erythema (20%). Significant BMI reduction was observed, supporting the clinical utility of setmelanotide in these populations