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

This case report describes a treatment success story for a very young child with a rare genetic condition that causes extreme hunger and obesity. The 2-year-old patient had leptin receptor deficiency, which means their body couldn't properly control appetite and weight. This led to constant, intense hunger (called hyperphagia), rapid weight gain, and delays in physical development like crawling and walking. The child was treated with a medication called setmelanotide, which is given as a daily injection under the skin. This drug works by targeting the brain pathways that control hunger and appetite. After starting treatment, the family saw significant improvements: the child's extreme hunger decreased, they ate less food, their weight improved, and they began reaching important developmental milestones like crawling and kneeling. The treatment continued successfully for nearly 2 years. This is encouraging news because setmelanotide is an FDA-approved treatment for several rare genetic conditions, including Bardet-Biedl Syndrome, that cause similar appetite and weight problems. While this medication can cause some side effects like skin changes, this case shows it can be safely used in very young children and may help families manage the challenging symptoms of these genetic conditions. The success in such a young patient suggests early treatment might be particularly beneficial.

Dysregulation of the melanocortin-4 receptor (MC4R) pathway can lead to severe hyperphagia and early-onset obesity. Symptoms may present before age 6 years, but there is limited clinical data on treatment outcomes in very young children. 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. This case report describes the use of setmelanotide in a 2-year-old child with hyperphagia and obesity due to LEPR deficiency. 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. Reported adverse events included skin rash and skin hyperpigmentation. Setmelanotide treatment started in a 2-year-old patient and continued for 23 months led to reductions in hyperphagia and food-seeking behavior, as well as improved motor skill function, BMI, and blood lipids. These findings support the use of setmelanotide in young children with hyperphagia and obesity due to LEPR deficiency.