Allan - Herndon - Dudley综合征（MCT8缺乏症）患者在儿童期表现出帕金森症状，并对左旋多巴/卡比多巴治疗有反应

IF 7.4 1区医学 Q1 CLINICAL NEUROLOGY

Movement Disorders Pub Date : 2025-03-15 DOI:10.1002/mds.30152

Nina-Maria Wilpert MD, PhD, Angela L. Hewitt MD, PhD, Roser Pons MD, PhD, Marie-Thérèse Henke MSc, Andrea Dell'Orco MSc, Martin Bauer MSc, Christiane Grolik MD, Stephan Menz, Monika Wahle, Annika Zink PhD, Alessandro Prigione MD, PhD, Christina Reinauer MD, Catharina Lange, Christian Furth MD, Knut Brockmann MD, Sabine Jung-Klawitter MD, Stine Christ MD, Angela M. Kaindl MD, Anna Tietze MD, PhD, Heiko Krude MD, Thomas Opladen MD, Markus Schuelke MD

{"title":"Allan - Herndon - Dudley综合征（MCT8缺乏症）患者在儿童期表现出帕金森症状，并对左旋多巴/卡比多巴治疗有反应","authors":"Nina-Maria Wilpert MD, PhD, Angela L. Hewitt MD, PhD, Roser Pons MD, PhD, Marie-Thérèse Henke MSc, Andrea Dell'Orco MSc, Martin Bauer MSc, Christiane Grolik MD, Stephan Menz, Monika Wahle, Annika Zink PhD, Alessandro Prigione MD, PhD, Christina Reinauer MD, Catharina Lange, Christian Furth MD, Knut Brockmann MD, Sabine Jung-Klawitter MD, Stine Christ MD, Angela M. Kaindl MD, Anna Tietze MD, PhD, Heiko Krude MD, Thomas Opladen MD, Markus Schuelke MD","doi":"10.1002/mds.30152","DOIUrl":null,"url":null,"abstract":"<div>\n \n \n <section>\n \n <h3> Background</h3>\n \n <p>Patients with mutations in the monocarboxylate transporter 8 (MCT8, <i>SLC16A2</i>) suffer from X-linked recessive Allan-Herndon-Dudley syndrome (AHDS), which is characterized by developmental delay and a severe movement disorder. Current trials using thyroid hormone derivatives to overcome the transporter defect have failed to achieve patient-oriented therapeutic goals.</p>\n </section>\n \n <section>\n \n <h3> Objectives</h3>\n \n <p>Our aim was to define the type of movement disorder in AHDS in an observational cohort study and to investigate the causative role of the dopaminergic system.</p>\n </section>\n \n <section>\n \n <h3> Methods</h3>\n \n <p>We present longitudinal clinical data from the DEEPTYPE registry of 11 patients with video documentation, standardized phenotyping, cerebrospinal fluid (CSF) analysis, neuroimaging data, and the treatment response to levodopa/carbidopa supplementation.</p>\n </section>\n \n <section>\n \n <h3> Results</h3>\n \n <p>Children presented with signs of childhood parkinsonism, including hypokinesia, hypomimia, inability to sit or stand, rigidity, dystonia, and autonomic dysfunction. CSF homovanillic acid concentrations were decreased (n = 12), suggesting an isolated dopamine pathway impairment. Seven out of 8 patients responded favorably to <span>l</span>-dopa/carbidopa supplementation and we did not observe any adverse drug reactions.</p>\n </section>\n \n <section>\n \n <h3> Conclusions</h3>\n \n <p>AHDS is associated with childhood parkinsonism, which is linked with biochemical abnormalities of dopamine metabolism. It can be treated with <span>l</span>-dopa/carbidopa supplementation. However, further research is needed to elucidate the exact effect of MCT8 deficiency on dopamine metabolism. © 2025 The Author(s). <i>Movement Disorders</i> published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.</p>\n </section>\n </div>","PeriodicalId":213,"journal":{"name":"Movement Disorders","volume":"40 5","pages":"938-949"},"PeriodicalIF":7.4000,"publicationDate":"2025-03-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/mds.30152","citationCount":"0","resultStr":"{\"title\":\"Patients with Allan-Herndon-Dudley Syndrome (MCT8 Deficiency) Display Symptoms of Parkinsonism in Childhood and Respond to Levodopa/Carbidopa Treatment\",\"authors\":\"Nina-Maria Wilpert MD, PhD, Angela L. Hewitt MD, PhD, Roser Pons MD, PhD, Marie-Thérèse Henke MSc, Andrea Dell'Orco MSc, Martin Bauer MSc, Christiane Grolik MD, Stephan Menz, Monika Wahle, Annika Zink PhD, Alessandro Prigione MD, PhD, Christina Reinauer MD, Catharina Lange, Christian Furth MD, Knut Brockmann MD, Sabine Jung-Klawitter MD, Stine Christ MD, Angela M. Kaindl MD, Anna Tietze MD, PhD, Heiko Krude MD, Thomas Opladen MD, Markus Schuelke MD\",\"doi\":\"10.1002/mds.30152\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div>\\n \\n \\n <section>\\n \\n <h3> Background</h3>\\n \\n <p>Patients with mutations in the monocarboxylate transporter 8 (MCT8, <i>SLC16A2</i>) suffer from X-linked recessive Allan-Herndon-Dudley syndrome (AHDS), which is characterized by developmental delay and a severe movement disorder. Current trials using thyroid hormone derivatives to overcome the transporter defect have failed to achieve patient-oriented therapeutic goals.</p>\\n </section>\\n \\n <section>\\n \\n <h3> Objectives</h3>\\n \\n <p>Our aim was to define the type of movement disorder in AHDS in an observational cohort study and to investigate the causative role of the dopaminergic system.</p>\\n </section>\\n \\n <section>\\n \\n <h3> Methods</h3>\\n \\n <p>We present longitudinal clinical data from the DEEPTYPE registry of 11 patients with video documentation, standardized phenotyping, cerebrospinal fluid (CSF) analysis, neuroimaging data, and the treatment response to levodopa/carbidopa supplementation.</p>\\n </section>\\n \\n <section>\\n \\n <h3> Results</h3>\\n \\n <p>Children presented with signs of childhood parkinsonism, including hypokinesia, hypomimia, inability to sit or stand, rigidity, dystonia, and autonomic dysfunction. CSF homovanillic acid concentrations were decreased (n = 12), suggesting an isolated dopamine pathway impairment. Seven out of 8 patients responded favorably to <span>l</span>-dopa/carbidopa supplementation and we did not observe any adverse drug reactions.</p>\\n </section>\\n \\n <section>\\n \\n <h3> Conclusions</h3>\\n \\n <p>AHDS is associated with childhood parkinsonism, which is linked with biochemical abnormalities of dopamine metabolism. It can be treated with <span>l</span>-dopa/carbidopa supplementation. However, further research is needed to elucidate the exact effect of MCT8 deficiency on dopamine metabolism. © 2025 The Author(s). <i>Movement Disorders</i> published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.</p>\\n </section>\\n </div>\",\"PeriodicalId\":213,\"journal\":{\"name\":\"Movement Disorders\",\"volume\":\"40 5\",\"pages\":\"938-949\"},\"PeriodicalIF\":7.4000,\"publicationDate\":\"2025-03-15\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://onlinelibrary.wiley.com/doi/epdf/10.1002/mds.30152\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Movement Disorders\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://onlinelibrary.wiley.com/doi/10.1002/mds.30152\",\"RegionNum\":1,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"CLINICAL NEUROLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Movement Disorders","FirstCategoryId":"3","ListUrlMain":"https://onlinelibrary.wiley.com/doi/10.1002/mds.30152","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"CLINICAL NEUROLOGY","Score":null,"Total":0}

引用次数: 0

摘要

单羧酸转运体8 （MCT8, SLC16A2）突变的患者患有X连锁隐性Allan - Herndon - Dudley综合征（AHDS），其特征是发育迟缓和严重的运动障碍。目前使用甲状腺激素衍生物来克服转运体缺陷的试验未能达到以患者为导向的治疗目标。我们的目的是通过一项观察性队列研究来确定AHDS的运动障碍类型，并探讨多巴胺能系统的致病作用。方法：我们收集了11例DEEPTYPE患者的纵向临床数据，包括视频记录、标准化表型、脑脊液（CSF）分析、神经影像学数据以及左旋多巴/卡比多巴补充剂的治疗反应。结果患儿表现出儿童帕金森病的症状，包括运动障碍、低血血症、不能坐下或站立、僵直、肌张力障碍和自主神经功能障碍。脑脊液同香草酸浓度降低（n = 12），提示孤立性多巴胺通路损伤。8名患者中有7名对左旋多巴/卡比多巴补充剂反应良好，我们没有观察到任何不良药物反应。结论sahds与儿童帕金森病相关，与多巴胺代谢生化异常有关。它可以用左旋多巴/卡比多巴补充剂治疗。然而，MCT8缺乏对多巴胺代谢的确切影响尚需进一步研究。©2025作者。Wiley期刊有限责任公司代表国际帕金森和运动障碍学会出版的《运动障碍》。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

查看原文本刊更多论文

Patients with Allan-Herndon-Dudley Syndrome (MCT8 Deficiency) Display Symptoms of Parkinsonism in Childhood and Respond to Levodopa/Carbidopa Treatment

Background

Patients with mutations in the monocarboxylate transporter 8 (MCT8, SLC16A2) suffer from X-linked recessive Allan-Herndon-Dudley syndrome (AHDS), which is characterized by developmental delay and a severe movement disorder. Current trials using thyroid hormone derivatives to overcome the transporter defect have failed to achieve patient-oriented therapeutic goals.

Objectives

Our aim was to define the type of movement disorder in AHDS in an observational cohort study and to investigate the causative role of the dopaminergic system.

Methods

We present longitudinal clinical data from the DEEPTYPE registry of 11 patients with video documentation, standardized phenotyping, cerebrospinal fluid (CSF) analysis, neuroimaging data, and the treatment response to levodopa/carbidopa supplementation.

Results

Children presented with signs of childhood parkinsonism, including hypokinesia, hypomimia, inability to sit or stand, rigidity, dystonia, and autonomic dysfunction. CSF homovanillic acid concentrations were decreased (n = 12), suggesting an isolated dopamine pathway impairment. Seven out of 8 patients responded favorably to l-dopa/carbidopa supplementation and we did not observe any adverse drug reactions.

Conclusions

AHDS is associated with childhood parkinsonism, which is linked with biochemical abnormalities of dopamine metabolism. It can be treated with l-dopa/carbidopa supplementation. However, further research is needed to elucidate the exact effect of MCT8 deficiency on dopamine metabolism. © 2025 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

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

Movement Disorders 医学-临床神经学

CiteScore

13.30

自引率

8.10%

发文量

371

审稿时长

12 months

期刊介绍： Movement Disorders publishes a variety of content types including Reviews, Viewpoints, Full Length Articles, Historical Reports, Brief Reports, and Letters. The journal considers original manuscripts on topics related to the diagnosis, therapeutics, pharmacology, biochemistry, physiology, etiology, genetics, and epidemiology of movement disorders. Appropriate topics include Parkinsonism, Chorea, Tremors, Dystonia, Myoclonus, Tics, Tardive Dyskinesia, Spasticity, and Ataxia.