BSPED2024 Poster Presentations Obesity 2 (7 abstracts)
Management of early onset obesity due to melanocortin 4 receptor (MC4R) defect with glucagon- like -peptide receptor agonist
Pon Gokul , Louise Apperley , Jennifer Parkinson , Anand Ramakrishnan , Shruti Mondkar , Nicola McConnell , Kate Clark , James O’Brien , Kim Lund , Ellie Clarke , Denise Swift & Senthil Senniappan
Alder Hey Children’s Hospital, Liverpool, United Kingdom
Introduction: Childhood obesity, has been linked to several nutritional and genetic factors. In some patients, monogenic causes can be identified, 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 of 2% to 6% in juvenile-onset obesity. We report the effect of Semaglutide (GLP1 analogue) in two adolescent patients with severe obesity due to heterozygous MCR4 mutation.
Discussion: Our first patient, a twelve-year-old boy, was referred to the tertiary weight management team for excessive weight gain since the age of one, consistently above the 99.6th percentile. He was diagnosed with insulin resistance, elevated HbA1c, dyslipidaemia, fatty liver, and a heterozygous MC4R alteration (E61K) inherited from his mother. Despite multidisciplinary lifestyle interventions, his weight reached 187.5 kg (BMI 56.5 kg/m²; body fat: 63.9%) at age 13. He began weekly Semaglutide, increasing from 0.5 mg to 1 mg. After 12 weeks, his BMI decreased to 52.2 kg/m² (weight 176.8 kg, body fat: 52.7%), with a 5.7% weight loss at 3 months and 11% at 12 months. Our second patient, a twelve-year-old girl, was referred to the weight management service for complications from excess weight, including raised intracranial pressure and sixth nerve palsy, which required surgical intervention. She had experienced excessive weight gain since age three. Despite initial treatment with daily GLP-1 analogues, Metformin, and lifestyle changes, her weight increased to 118.8 kg (BMI 49.6 kg/m², body fat 66.5%) by age 13. She was then started on Semaglutide, dose gradually increased from 0.5 to 1.7 mg weekly. This led to a 6.8% weight loss at 3 months and 9.2% at 9 months, weight at 106 kg (BMI 43.6 kg/m², body fat 61.4%), with improvements in dyslipidaemia, insulin resistance, and overall health.
Conclusion: Semaglutide has proven to be useful for our patients with MC4R mutations experiencing rapid weight gain and related complications. GLP-1 analogues may help counteract MC4R-related appetite dysregulation, proving beneficial for those with this mutation.
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Endocrine Abstracts
ISSN 1470-3947 (print) | ISSN 1479-6848 (online)
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