Endocrine Abstracts

Background: Bardet-Biedl syndrome (BBS) is a rare genetic condition characterised by ciliary protein dysfunction leading to multi-organ damage. Patients with BBS can suffer from hyperphagia and severe obesity from childhood and associated weight-related comorbid diseases such as type 2 diabetes and hypertension. However, the optimal weight management strategy and response to weight loss pharmacotherapy is unknown.

Case presentation: We present a case of a woman aged 28 who attended our weight management service with a history of hyperphagia and obesity since early childhood. Her body mass index (BMI) was 37.9 kg/m2 on presentation. She also had a history of type 2 diabetes, hypothyroidism, acanthosis nigricans, hypertension, polycystic ovarian syndrome, and retinitis pigmentosa. A clinical diagnosis of Bardet-Biedl syndrome (BBS) was suspected, and genetic testing by Sanger sequencing confirmed homozygous c. 1599_1602del p. (Thr53411efs*21) in the BBS10 gene (12q21.2). Management was focused on weight reduction with dietitian input. A trial of canagliflozin achieved initial weight reduction followed by rapid weight regain. Canagliflozin was stopped and Liraglutide was subsequently initiated. Liraglutide resulted in significant weight loss over a five-month period with reduction in BMI to 33.5 kg/m2. Following patient preference, Liraglutide was switched to Semaglutide for the convenience of once weekly injections. Following 19 months of treatment with Semaglutide, there was further weight loss, achieving a BMI of 24.3 kg/m2.

Discussion: GLP1RA therapy in our patient with BBS led to a significant total weight reduction of 33% within 30 months of treatment. Long-term weight maintenance and metabolic benefits of continued GLP1RA therapy remain to be seen.

Conclusion: We report significant weight reduction utilising GLP1RA therapy in a patient with genetic obesity due to BBS. Liraglutide and Semaglutide were associated with substantial reduction in body weight. This provides a novel therapeutic approach for obesity management in patients with rare genetic disorders such as BBS.