ESPE Abstracts

Background: Congenial Leptin deficiency (CLD) manifests as severe obesity, hyperphagia, and metabolic complications. While Metroleptin is the treatment of choice, its cost makes it inaccessible for many. We present two sisters, aged 14 and 7, diagnosed with CLD, who had significant improvement with the glucagon-like peptide-1 (GLP-1) receptor agonist, Semaglutide. Both experienced notable reduction in body weight and metabolic markers with Semaglutide, highlighting its potential as a novel treatment for patients unable to afford Metroleptin.

Case Presentation: In this family, three children were diagnosed with CLD due to a homozygous leptin gene mutation. One of them, a male, passed away at age 3 due to obesity-related complications. The two sisters, aged 14 and 7, presented with severe obesity and hyperphagia, but treatment with Metroleptin was financially unfeasible. Consequently, both began Semaglutide therapy alongside nutritional management, adjusting dosages to manage side effects.

Patient 1: A 14-year-old female presented with severe obesity (BMI 47.73 kg/m², BMI SD 2.77), hyperphagia, GERD, and pre-diabetes (A1c 6.3%). After initiating Semaglutide (starting dose 0.5 mg weekly, titrated up to 1 mg weekly), her weight decreased from 117.35 kg to 109.55 kg over 6 months, with a corresponding drop in BMI (44.96 kg/m², BMI SD 2.66) and A1c to 5.8%.

Patient 2: aged 7, initially treated with Liraglutide (0.6 mg, titrated up to 1.8 mg daily) for early-onset obesity, fatty liver, and hyperphagia, switched to Semaglutide (same dosage protocol) when available. After 12 months, with the initial 6 months of non-compliance with Liraglutide, her weight decreased from 83.50 kg to 79.00 kg. Her BMI dropped from 47.78 kg/m² to 42.71 kg/m² with improvements in A1c and liver enzymes were observed (ALT decreasing from 163 IU/L to 37 IU/L and AST from 154 IU/L to 25 IU/L). Both patients responded positively to Semaglutide, experiencing significant weight loss and metabolic improvements. Patient 1 achieved a 6.6% reduction in body weight and normalized A1c, while Patient 2 showed a 5.3% weight reduction alongside metabolic enhancements. Importantly, both reported decreased hunger and improved adherence to nutritional recommendations, enhancing their overall quality of life.

Conclusion: This case underscores the effectiveness of GLP-1 agonists in reducing appetite in CLD patients. Semaglutide therapy led to notable weight loss and metabolic improvements in the two sisters. However, further research is essential to understand its long-term efficacy and safety in pediatric CLD populations and to refine treatment protocols for those unable to afford Metroleptin.