儿童和青少年肥胖的患病率正在增加,它被认为是一种复杂的疾病,通常始于儿童早期,并持续一生。多基因和单基因肥胖都受到遗传易感性和环境因素的共同影响。罕见的遗传性肥胖形式是由对体重调节有重大影响的单个基因中的特定致病变异引起的。特别是涉及瘦素-黑皮质素途径的基因。对于在婴儿期表现出快速体重增加并显示出提示单基因肥胖的其他临床特征的患者,建议进行基因检测,因为早期识别可以进行适当的治疗。预防肥胖相关并发症的发展,避免传统治疗方法的失败。在过去,控制儿童和青少年肥胖的主要建议集中在改变多种生活方式,解决饮食问题,身体活动,和行为,目的是长期维持这些变化。然而,仅通过生活方式干预实现实质性和持久的体重减轻和体重指数(BMI)改善是罕见的。最近,遗传分析取得的进展为针对不同形式的遗传性肥胖的创新药物治疗铺平了道路。通过了解导致肥胖发展的分子途径,现在,根据其独特的遗传机制,确定可以从靶向治疗中获益的特定患者是可行的。结论:然而,需要在儿科人群中进行额外的临床前研究和研究,制定更个性化的预防和治疗方案,特别是为了尽早实施创新和有益的管理方案,并使这些新的治疗方法转化为临床实践。什么是已知的:•肥胖在儿科人群中的患病率正在增加,它被认为是一种多方面的状况,通常始于儿童早期,并持续存在于成人生活中。特别是,罕见的遗传形式的肥胖受到遗传易感性和环境因素的共同影响,并且是由单个基因中的特定致病变异引起的,显示出对体重调节的显着影响。特别是涉及瘦素-黑皮质素途径的基因。•在婴儿期体重快速增加并表现出单基因肥胖的其他临床特征的患者应进行基因检测。which,通过正确的诊断,可以通过确定适当的治疗方法来预防肥胖相关后果的发展。最新动态:•近年来,基因分析的进步使开发各种形式的遗传性肥胖的创新药物治疗成为可能。事实上,现在可以通过了解肥胖发展中涉及的分子途径,根据其独特的遗传机制,确定可以从靶向治疗中获益的特定患者。•正如过去几年所证明的那样,两种药物,Setmelanotide和metreleptin,已被确定为治疗某些罕见形式的单基因肥胖的潜在有效干预措施,这些单基因肥胖是由瘦素-黑皮质素途径相关基因的功能丧失突变引起的。最近的进步导致了新的治疗方法的发展,包括利拉鲁肽,司马鲁肽和retatrutide,它们有可能预防代谢异常的进展,并改善这些罕见和严重肥胖个体的预后。然而,广泛的临床前研究和,具体来说,在儿科人群中进行更多的研究是必要的,以促进这些创新的治疗技术转化为临床实践。
The prevalence of obesity in children and adolescents is increasing, and it is recognised as a complex disorder that often begins in early childhood and persists throughout life. Both polygenic and monogenic obesity are influenced by a combination of genetic predisposition and environmental factors. Rare genetic obesity forms are caused by specific pathogenic variants in single genes that have a significant impact on weight regulation, particularly genes involved in the leptin-melanocortin pathway. Genetic testing is recommended for patients who exhibit rapid weight gain in infancy and show additional clinical features suggestive of monogenic obesity as an early identification allows for appropriate treatment, preventing the development of obesity-related complications, avoiding the failure of traditional treatment approaches. In the past, the primary recommendations for managing obesity in children and teenagers have been focused on making multiple lifestyle changes that address diet, physical activity, and behaviour, with the goal of maintaining these changes long-term. However, achieving substantial and lasting weight loss and improvements in body mass index (BMI) through lifestyle interventions alone is rare. Recently the progress made in genetic analysis has paved the way for innovative pharmacological treatments for different forms of genetic obesity. By understanding the molecular pathways that contribute to the development of obesity, it is now feasible to identify specific patients who can benefit from targeted treatments based on their unique genetic mechanisms. Conclusion: However, additional preclinical research and studies in the paediatric population are required, both to develop more personalised prevention and therapeutic programs, particularly for the early implementation of innovative and beneficial management options, and to enable the translation of these novel therapy approaches into clinical practice. What is Known: • The prevalence of obesity in the paediatric population is increasing, and it is considered as a multifaceted condition that often begins in early childhood and persists in the adult life. Particularly, rare genetic forms of obesity are influenced by a combination of genetic predisposition and environmental factors and are caused by specific pathogenic variants in single genes showing a remarkable impact on weight regulation, particularly genes involved in the leptin-melanocortin pathway. • Patients who present with rapid weight gain in infancy and show additional clinical characteristics indicative of monogenic obesity should undergo genetic testing, which, by enabling a correct diagnosis, can prevent the development of obesity-related consequences through the identification for appropriate treatment. What is New: • In recent years, advances made in genetic analysis has made it possible to develop innovative pharmacological treatments for various forms of genetic obesity. In fact, it is now achievable to identify specific patients who can benefit from targeted treatments based on their unique genetic mechanisms by understanding the molecular pathways involved in the development of obesity. • As demonstrated over the last years, two drugs, setmelanotide and metreleptin, have been identified as potentially effective interventions in the treatment of certain rare forms of monogenic obesity caused by loss-of-function mutations in genes involved in the leptin-melanocortin pathway. Recent advancements have led to the development of novel treatments, including liraglutide, semaglutide and retatrutide, that have the potential to prevent the progression of metabolic abnormalities and improve the prognosis of individuals with these rare and severe forms of obesity. However, extensive preclinical research and, specifically, additional studies in the paediatric population are necessary to facilitate the translation of these innovative treatment techniques into clinical practice.