两名复合杂合子瘦素受体缺乏症患者的诊断和治疗奥德赛。

IF 2.4 Q1 PEDIATRICS Molecular and cellular pediatrics Pub Date : 2020-11-03 DOI:10.1186/s40348-020-00107-3
Stefanie Zorn, Julia von Schnurbein, Katja Kohlsdorf, Christian Denzer, Martin Wabitsch
{"title":"两名复合杂合子瘦素受体缺乏症患者的诊断和治疗奥德赛。","authors":"Stefanie Zorn, Julia von Schnurbein, Katja Kohlsdorf, Christian Denzer, Martin Wabitsch","doi":"10.1186/s40348-020-00107-3","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>Rare genetic variations in the leptin-melanocortin signalling pathway can severely impair appetite regulation and cause extreme obesity in early childhood.</p><p><strong>Case presentation: </strong>Our case reports describe the diagnostic and therapeutic procedures in a girl as well as in a non-related boy of non-consanguineous, German parents with severe early-onset obesity, pronounced hyperphagia, and permanent food-seeking behaviour. Excessive weight gain within the first year of life initiated extensive diagnostics without finding a causal diagnosis. Furthermore, a wide range of intensive, interdisciplinary, and behavioural therapies for weight control were unsuccessful. Prior to bariatric surgery, the 18-year-old girl and the 14-year-old boy reached a BMI of 67.7 kg/m<sup>2</sup> and 55.2 kg/m<sup>2</sup>, respectively. However, even surgical outcomes were unsatisfactory. A subsequently initiated genetic analysis including sequencing of the leptin receptor gene revealed compound heterozygous variants as a cause of the severe early-onset obesity in both patients (c.2598-3_2607delTAGAATGAAAAAG and c.2227 T>C; c.1874G>A and c.2051A>C). Both patients were enrolled in the clinical study RM-493-015 and treated with melanocortin receptor agonist setmelanotide. Currently, they are still on setmelanotide treatment in the extension trial RM-493-022.</p><p><strong>Conclusion: </strong>Our case report illustrates the urgent necessity of early genetic diagnostics in children with severe early-onset obesity to avoid frustrating and potentially damaging therapies. Thus, genetic examination should precede bariatric surgery. In the future, several pharmacological therapies will be available for some forms of monogenetic obesity.</p>","PeriodicalId":74215,"journal":{"name":"Molecular and cellular pediatrics","volume":"7 1","pages":"15"},"PeriodicalIF":2.4000,"publicationDate":"2020-11-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7606406/pdf/","citationCount":"0","resultStr":"{\"title\":\"Diagnostic and therapeutic odyssey of two patients with compound heterozygous leptin receptor deficiency.\",\"authors\":\"Stefanie Zorn, Julia von Schnurbein, Katja Kohlsdorf, Christian Denzer, Martin Wabitsch\",\"doi\":\"10.1186/s40348-020-00107-3\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>Rare genetic variations in the leptin-melanocortin signalling pathway can severely impair appetite regulation and cause extreme obesity in early childhood.</p><p><strong>Case presentation: </strong>Our case reports describe the diagnostic and therapeutic procedures in a girl as well as in a non-related boy of non-consanguineous, German parents with severe early-onset obesity, pronounced hyperphagia, and permanent food-seeking behaviour. Excessive weight gain within the first year of life initiated extensive diagnostics without finding a causal diagnosis. Furthermore, a wide range of intensive, interdisciplinary, and behavioural therapies for weight control were unsuccessful. Prior to bariatric surgery, the 18-year-old girl and the 14-year-old boy reached a BMI of 67.7 kg/m<sup>2</sup> and 55.2 kg/m<sup>2</sup>, respectively. However, even surgical outcomes were unsatisfactory. A subsequently initiated genetic analysis including sequencing of the leptin receptor gene revealed compound heterozygous variants as a cause of the severe early-onset obesity in both patients (c.2598-3_2607delTAGAATGAAAAAG and c.2227 T>C; c.1874G>A and c.2051A>C). Both patients were enrolled in the clinical study RM-493-015 and treated with melanocortin receptor agonist setmelanotide. Currently, they are still on setmelanotide treatment in the extension trial RM-493-022.</p><p><strong>Conclusion: </strong>Our case report illustrates the urgent necessity of early genetic diagnostics in children with severe early-onset obesity to avoid frustrating and potentially damaging therapies. Thus, genetic examination should precede bariatric surgery. In the future, several pharmacological therapies will be available for some forms of monogenetic obesity.</p>\",\"PeriodicalId\":74215,\"journal\":{\"name\":\"Molecular and cellular pediatrics\",\"volume\":\"7 1\",\"pages\":\"15\"},\"PeriodicalIF\":2.4000,\"publicationDate\":\"2020-11-03\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7606406/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Molecular and cellular pediatrics\",\"FirstCategoryId\":\"1085\",\"ListUrlMain\":\"https://doi.org/10.1186/s40348-020-00107-3\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"PEDIATRICS\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Molecular and cellular pediatrics","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.1186/s40348-020-00107-3","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"PEDIATRICS","Score":null,"Total":0}
引用次数: 0

摘要

背景:瘦素-黑色素皮质素信号通路中的罕见基因变异会严重影响食欲调节,导致幼儿期极度肥胖:我们的病例报告描述了一个女孩和一个非亲缘关系男孩的诊断和治疗过程,他们的父母都是德国人,非近亲结婚,患有严重的早发性肥胖症、明显的多食和永久性觅食行为。出生后第一年体重增长过快,医生对其进行了广泛的诊断,但没有找到病因。此外,为控制体重而采取的各种强化、跨学科和行为疗法均未奏效。在接受减肥手术之前,18 岁女孩和 14 岁男孩的体重指数分别为 67.7 kg/m2 和 55.2 kg/m2。然而,即使是手术结果也不尽如人意。随后启动的基因分析(包括瘦素受体基因测序)发现,复合杂合变体是导致这两名患者早发严重肥胖症的原因(c.2598-3_2607delTAGAATGAAAAAG 和 c.2227T>C;c.1874G>A 和 c.2051A>C)。这两名患者都参加了 RM-493-015 临床研究,并接受了黑色素皮质素受体激动剂 Setmelanotide 的治疗。目前,他们仍在 RM-493-022 扩展试验中接受塞美拉诺肽治疗:我们的病例报告说明,对于早发重度肥胖症患儿,迫切需要尽早进行基因诊断,以避免令人沮丧且可能造成损害的治疗。因此,在进行减肥手术前应先进行遗传学检查。未来,将有多种药物疗法可用于治疗某些形式的单基因肥胖症。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

摘要图片

查看原文
分享 分享
微信好友 朋友圈 QQ好友 复制链接
本刊更多论文
Diagnostic and therapeutic odyssey of two patients with compound heterozygous leptin receptor deficiency.

Background: Rare genetic variations in the leptin-melanocortin signalling pathway can severely impair appetite regulation and cause extreme obesity in early childhood.

Case presentation: Our case reports describe the diagnostic and therapeutic procedures in a girl as well as in a non-related boy of non-consanguineous, German parents with severe early-onset obesity, pronounced hyperphagia, and permanent food-seeking behaviour. Excessive weight gain within the first year of life initiated extensive diagnostics without finding a causal diagnosis. Furthermore, a wide range of intensive, interdisciplinary, and behavioural therapies for weight control were unsuccessful. Prior to bariatric surgery, the 18-year-old girl and the 14-year-old boy reached a BMI of 67.7 kg/m2 and 55.2 kg/m2, respectively. However, even surgical outcomes were unsatisfactory. A subsequently initiated genetic analysis including sequencing of the leptin receptor gene revealed compound heterozygous variants as a cause of the severe early-onset obesity in both patients (c.2598-3_2607delTAGAATGAAAAAG and c.2227 T>C; c.1874G>A and c.2051A>C). Both patients were enrolled in the clinical study RM-493-015 and treated with melanocortin receptor agonist setmelanotide. Currently, they are still on setmelanotide treatment in the extension trial RM-493-022.

Conclusion: Our case report illustrates the urgent necessity of early genetic diagnostics in children with severe early-onset obesity to avoid frustrating and potentially damaging therapies. Thus, genetic examination should precede bariatric surgery. In the future, several pharmacological therapies will be available for some forms of monogenetic obesity.

求助全文
通过发布文献求助,成功后即可免费获取论文全文。 去求助
来源期刊
CiteScore
2.20
自引率
0.00%
发文量
0
期刊最新文献
Early metabolic and hemodynamic indicators of kidney dysfunction in mice offspring from parental low protein diet. Fatty acids from nutrition sources for preterm infants and their effect on plasma fatty acid profiles. Description of bone health in adolescents and young persons with Klinefelter syndrome – results from a pilot study Monogenic lupus – from gene to targeted therapy B cell academy of the gut: an update on gut associated germinal centre B cell dynamics.
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
现在去查看 取消
×
提示
确定
0
微信
客服QQ
Book学术公众号 扫码关注我们
反馈
×
意见反馈
请填写您的意见或建议
请填写您的手机或邮箱
已复制链接
已复制链接
快去分享给好友吧!
我知道了
×
扫码分享
扫码分享
Book学术官方微信
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术
文献互助 智能选刊 最新文献 互助须知 联系我们:info@booksci.cn
Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。
Copyright © 2023 Book学术 All rights reserved.
ghs 京公网安备 11010802042870号 京ICP备2023020795号-1