ESPE Abstracts

Introduction: Childhood obesity is a growing concern worldwide, and it has been linked to several nutritional and genetic factors. In some patients, monogenic causes can be identified, which are due to single gene mutations in specific pathways related to appetite regulation. One of the most common monogenic causes of obesity is heterozygous mutations in Melanocortin 4 receptor (MC4R), with a prevalence ranging from 2% to 6% in juvenile-onset obesity. We report the effect of Semaglutide (GLP1 analogue) in an adolescent boy with severe obesity due to heterozygous MCR4 mutation.

Discussion: A twelve-year-old boy was referred to the tertiary MDT weight management team for concerns of excessive weight gain since one year of age. He was born at term with a birth weight 3.57kg (50th centile). Weight was always above 99.6th centile after 1 year of age. He was diagnosed with autism at the age of 5 years. His mobility was hampered by his weight gain. The investigations revealed insulin resistance, normal fasting glucose and HbA1c, dyslipidemia and fatty liver. The genetic workup confirmed a heterozygous alteration in MCR4 [E61K] (inherited from mother). His management was particularly challenging in view of his exponential weight gain, needle phobia and behaviour difficulties. Intense multidisciplinary lifestyle intervention was not successful, and the patient continued to gain weight to a peak of 187.5kg (BMI 56.5kg/m2; body fat: 63.9%) at the age of 13 years. He was started on weekly Semaglutide at a dose of 0.5mg and gradually increased to 1mg weekly. Due to his severe autism and needle phobia, it was agreed that weekly injections would be the most suitable treatment option alongside lifestyle modification. After 12 weeks of Semaglutide treatment, his BMI decreased to 52.2kg/m2 (weight 176.8kg, body fat: 52.7%). Weight loss of 5.7% and 9.8% was recorded at 3- and 6-months post Semaglutide respectively.

Conclusion: We report a significant weight loss following weekly GLP1 analogue therapy in a patient with MC4R mutation and rapid weight gain leading to complications. MC4R receptor has been considered as a potential drug target for the treatment of monogenic obesity. GLP-1 analogues could circumvent MC4R-induced appetite regulation and thereby constitute a treatment option for individuals with MC4R mutations. A holistic approach that combines lifestyle modification, behavioural intervention, and pharmacological treatment is required to manage severe obesity in children and young people.