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利拉鲁肽治疗一名患有基因变异的病态肥胖青少年:副作用降低了治疗成功率。

Liraglutide Treatment in a Morbidly Obese Adolescent with a Gene Variant: Side Effects Reduce Success.

作者信息

Çamtosun Emine, Akıncı Ayşehan, Kayaş Leman, Çiftçi Nurdan, Tekedereli İbrahim

机构信息

İnönü University Faculty of Medicine, Department of Pediatric Endocrinology, Malatya, Turkey

İnönü University Faculty of Medicine, Department of Medical Biology and Genetics, Malatya, Turkey

出版信息

J Clin Res Pediatr Endocrinol. 2023 May 29;15(2):225-229. doi: 10.4274/jcrpe.galenos.2021.2021.0158. Epub 2021 Sep 29.

Abstract

Variants of the melanocortin-4 receptor () gene are the most common cause of monogenic obesity. It has been shown that, while obesity cannot be controlled with diet and exercise, glucagon-like-peptide-1 receptor agonists (GLP-1 RA) provide weight loss in the short term. In this paper, our experience with liraglutide treatment in an adolescent patient carrying a gene variant is presented. A female patient was admitted first at the age of 12.5 years with a complaint of progressive weight gain. She had marked excess of appetite since infancy. On physical examination of the pubertal female patient with a body mass index (BMI) of 36.1 kg/m (3.48 standard deviation score), there was no pathological finding except diffuse acanthosis nigricans. Laboratory examinations revealed only insulin resistance. Weight loss was not achieved with lifestyle changes, metformin and orlistat treatments. On genetic examination, a sporadic heterozygous c.206T>G(p.I69R) variant that had been reported previously, was found in gene. Treatment with the GLP-1 RA, liraglutide, was initiated and a 19.2% reduction was achieved in the body weight and BMI at the end of 32 weeks. However, the patient, whose treatment compliance was disrupted due to significant gastrointestinal complaints, returned to her former weight within a few months (13 weeks) after treatment was stopped. In this case with a known pathogenic variant in gene, decrease of appetite and weight loss were achieved with liraglutide treatment, but side-effects of this treatment led to discontinuation of therapy. In such cases, there is need for effective and tolerable treatment options.

摘要

黑皮质素-4受体()基因变异是单基因肥胖最常见的病因。研究表明,虽然饮食和运动无法控制肥胖,但胰高血糖素样肽-1受体激动剂(GLP-1 RA)在短期内可实现体重减轻。本文介绍了我们对一名携带基因变异的青少年患者使用利拉鲁肽治疗的经验。一名女性患者12.5岁时首次入院,主诉体重渐进性增加。自婴儿期起,她就有明显的食欲亢进。对这名青春期女性患者进行体格检查,其体重指数(BMI)为36.1 kg/m(标准差评分3.48),除弥漫性黑棘皮病外无病理发现。实验室检查仅显示胰岛素抵抗。通过生活方式改变、二甲双胍和奥利司他治疗均未实现体重减轻。基因检测发现该基因存在一个先前已报道的散发性杂合c.206T>G(p.I69R)变异。开始使用GLP-1 RA利拉鲁肽进行治疗,32周结束时体重和BMI降低了19.2%。然而,由于严重的胃肠道不适导致治疗依从性中断,该患者在停药后几个月(13周)内恢复到以前的体重。在这个已知基因存在致病变异的病例中,利拉鲁肽治疗实现了食欲下降和体重减轻,但这种治疗的副作用导致治疗中断。在这种情况下,需要有效且可耐受的治疗选择。

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Mutations in the melanocortin 4 receptor (MC4R) gene in obese patients in Norway.挪威肥胖患者中黑皮质素4受体(MC4R)基因的突变
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