ESPE Abstracts

Introduction: LEPR regulates body mass via a negative feedback mechanism between adipose tissue and the hypothalamus. Leptin resistance is characterized by reduced satiety, over-consumption of nutrients, and increased total body mass. Often this leads to obesity, which reduces the effectiveness of using exogenous leptin as a therapeutic agent. Setmelanotide is an approved treatment for severe obesity due to LEPR in patients older than 6 years old.

Clinical Case: We show a 2 years-old girl, whose parents reported a gain of 1 kg per week since she was a few months of life. Furthermore, they stated that she had a great appetite for food. They reported that she was not satisfied even if she ate. She was demanding food all time, even between meals. Constipated habit. She had anthropometry at birth normal. No personal history of problems with sucking, tone, sociability or development. No family history of obesity. In the dietary survey, no major transgressions were detected. Analyzes for metabolic study and Magnetic Resonance Imaging (MRI) of the abdomen were normal. Cranial MRI showed a pituitary gland with normal morphology but a slight decrease in its craniocaudal diameter. In genetic study were identified an apparent homozygosity of a variant of uncertain clinical significance (VSI) in LEPR gene (NM_002303.6:c.2357T>C p.(Leu786Pro)). Additionally, the presence of 7 polymorphisms associated with susceptibility to obesity were identified. After these results and after a year of follow-up with progressive weight gain despite good adherence to dietary measures, it was decided to include her in a setmelatonide therapeutic trial, instead of her age at this moment (4 years old). She remained in treatment for two years until the end of the trial, achieving a weight loss of 3 kg and a loss of Body Mass Index (BMI) of -7.02 SD in the first 15 months. After this, she recovered 2SD BMI although she maintained better control of the feeling of satiety from the first moment, which allowed her to have fewer limitations in her daily life. During this entire treatment period she had an episode of arrhythmia without pathological significance and an increase in her skin tone, without other incidents.

Conclusion: This case supports setmelanotide as a safe treatment for obesity and hyperphagia caused by LEPR deficiency, even in patients under 6 years of age.