SAT-707 - Weight Management in Bardet-Biedl Syndrome: A Case of Hyperphagia Responsive to GLP-1 Therapy

Introduction
Bardet-Biedl Syndrome (BBS) is a rare genetic disorder. It features several symptoms, including retinitis pigmentosa, obesity, and hyperphagia. Managing obesity in BBS is very challenging because of hypothalamic issues related to appetite. We present the case of a young woman with BBS and severe obesity who had a strong response to GLP-1 receptor agonist therapy.

Case Presentation
The patient is a 29-year-old woman with a history of Bardet-Biedl Syndrome diagnosed in 2013. She has retinitis pigmentosa, severe obesity, intracranial hypertension, scoliosis, and has undergone cholecystectomy and hernia repair. In 2012, she had endoscopic sleeve gastrectomy when her weight was around 150 kg. Although she lost weight initially, she regained it, peaking near 200 kg. She does not report any other issues and is otherwise stable. Her vital signs are normal: Temperature: 36.5°C, Heart Rate: 106 bpm, Blood Pressure: 116/83 mmHg, SpO2: 98% on room air.

The patient started tirzepatide (Mounjaro), a dual GIP/GLP-1 receptor agonist, about six months ago. She reported a great response, with better control of hyperphagia and significant weight loss. Therapy was paused for two months due to an upcoming surgery. Currently, her weight is 145.2 kg, her height is 162.6 cm, and her BMI is about 55, indicating she has lost over 30% of her body weight. She intends to resume Mounjaro and seeks help with injections.

Discussion
Obesity in BBS arises from genetic defects that disrupt signals of fullness through the melanocortin-4 receptor (MC4R) pathway. This leads to hyperphagia and early obesity. Traditional lifestyle changes usually provide limited results due to underlying brain dysfunction. Medications that target appetite control have become a hopeful approach in treating syndromic obesity.

An alternative treatment, setmelanotide (IMCIVREE), received FDA approval in 2022 specifically for BBS. In a major 66-week clinical trial with 44 patients aged six or older with obesity and a clinical diagnosis of BBS, the average BMI reduction after 52 weeks was 7.9%. About 39% of participants achieved at least a 10% BMI reduction. However, our patient experienced over a 30% weight loss with tirzepatide. Although setmelanotide is FDA approved for obesity related to BBS, its use has several limitations. It is much more expensive than GLP-1 receptor agonists, making insurance coverage and prior authorization tougher. Another concern is skin darkening, which could affect the quality of life and adherence to treatment. Given these factors and the patient’s outstanding response to tirzepatide, continuing GLP-1 therapy is justified both clinically and financially in this case. More research is necessary to understand how patients respond to GLP-1 receptor agonists in syndromic obesity like Bardet-Biedl Syndrome.

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