Clinical Improvements with Setmelanotide in a 2-Year-Old Patient with Hyperphagia and Obesity due to Leptin Receptor Deficiency: A Case Report.

introductionDysregulation of the melanocortin-4 receptor (MC4R) pathway can lead to hyperphagia and early-onset obesity. Setmelanotide, an MC4R agonist, is approved for patients age ≥2 years with rare MC4R pathway disease due to Bardet-Biedl syndrome, pro-opiomelanocortin or proprotein convertase subtilisin/kexin type 1 deficiency, or leptin receptor (LEPR) deficiency, but there are limited clinical data on treatment outcomes in very young children. This case report describes the use of setmelanotide in a 2-year-old child with hyperphagia and obesity due to LEPR deficiency. CASE DESCRIPTION: The patient presented with early-onset hyperphagia, rapid weight gain, and obesity-associated delays in motor development. Following a medical assessment in May 2021, he was diagnosed with LEPR deficiency. Setmelanotide treatment via subcutaneous injection was initiated in March 2023 (patient age 2 years 4 months) at a dose of 0.5 mg/day, increased to 2.5 mg/day in 0.5 mg increments, and the patient was followed for 23 months. Following treatment initiation, significant clinical improvements were observed, including reductions in hyperphagia, food intake and cravings, and body mass index (BMI). Motor skill function also improved, with the child achieving milestones such as crawling and kneeling. Significant improvements in caregivers' QoL were also reported. Reported adverse events included skin rash and skin hyperpigmentation.

conclusionSetmelanotide treatment started in a 2-year-old patient and continued for 23 months led to improvements in hyperphagia, BMI, and blood lipids and led to significant improvements in caregivers' QoL. Improved motor skill function was also seen with as BMI decreased. These findings support the use of setmelanotide in young children with hyperphagia and obesity due to LEPR deficiency.