Beales Philip L, Cetiner Metin, Haqq Andrea M, Miller Jennifer, Shoemaker Ashley H, Valverde Diana, Zacchia Miriam, Dollfus Hélène
UCL Great Ormond Street Institute of Child Health, London, UK.
Children's Hospital, Pediatrics II, University of Essen, Essen, Germany.
Obes Rev. 2025 Jul;26(7):e13915. doi: 10.1111/obr.13915. Epub 2025 Apr 4.
Bardet-Biedl syndrome (BBS) is a rare, genetically heterogeneous, and highly pleiotropic autosomal recessive ciliopathy. Patients typically present with early loss of vision, hyperphagia, severe obesity, learning difficulties, and renal dysfunction. In patients with BBS, dysfunction of the immotile primary cilia in the hypothalamic melanocortin-4 receptor (MC4R) pathway responsible for controlling energy balance, hunger, and satiety results in severe hyperphagia manifesting in food-seeking behaviors that drive the development of obesity early in childhood. These behaviors have negative impacts on many areas of the lives of patients with BBS and their families/caregivers, including sleep, mood, school/work, and social/family relationships. Additionally, many patients feel stigmatized due to their hyperphagia-associated food-seeking behaviors and the resulting obesity, which exacerbates the impacts of hyperphagia on quality of life. Early identification and management of hyperphagia in patients with BBS is key: mitigating food-seeking and weight gain can improve quality of life and reduce the risk of metabolic and cardiovascular diseases that is increased in patients with BBS. Until recently, the only treatment strategies available were lifestyle and diet modifications. However, targeted treatment with the novel MC4R agonist setmelanotide now offers an effective management option to reduce hyperphagia and weight in patients with BBS, improving overall health and quality of life.
巴德-比德尔综合征（BBS）是一种罕见的、基因异质性的、具有高度多效性的常染色体隐性纤毛病。患者通常表现为早期视力丧失、食欲亢进、严重肥胖、学习困难和肾功能障碍。在BBS患者中，负责控制能量平衡、饥饿和饱腹感的下丘脑黑皮质素-4受体（MC4R）通路中不动初级纤毛功能障碍导致严重的食欲亢进，表现为觅食行为，从而在儿童早期推动肥胖的发展。这些行为对BBS患者及其家庭/照顾者生活的许多方面都有负面影响，包括睡眠、情绪、学校/工作以及社会/家庭关系。此外，许多患者因与食欲亢进相关的觅食行为和由此导致的肥胖而感到受辱，这加剧了食欲亢进对生活质量的影响。早期识别和管理BBS患者的食欲亢进至关重要：减轻觅食行为和体重增加可以改善生活质量，并降低BBS患者中增加的代谢和心血管疾病风险。直到最近，唯一可用的治疗策略是生活方式和饮食调整。然而，新型MC4R激动剂setmelanotide的靶向治疗现在为减轻BBS患者的食欲亢进和体重提供了一种有效的管理选择，改善了整体健康和生活质量。
