Hao Jian, Kelly Dorothy I, Su Jianzhong, Pascual Juan M
Department of Mathematics, University of Texas at Arlington, Arlington.
Rare Brain Disorders Program, Department of Neurology and Neurotherapeutics, University of Texas Southwestern Medical Center, Dallas.
JAMA Neurol. 2017 Jun 1;74(6):727-732. doi: 10.1001/jamaneurol.2017.0298.
Case reports regularly document unique or unusual aspects of glucose transporter type 1 deficiency (G1D). In contrast, population studies from which to draw global inferences are lacking. Twenty-five years after the earliest case reports, this deficiency still particularly affects treatment and prognostic counseling.
To examine the most common features of G1D.
DESIGN, SETTING, AND PARTICIPANTS: In this study, data were collected electronically from 181 patients with G1D through a web-based, worldwide patient registry from December 1, 2013, through December 1, 2016. The study used several statistical methods tailored to address the age at onset of various forms of G1D, associated manifestations, natural history, treatment efficacy, and diagnostic procedures. These factors were correlated in a predictive mathematical model designed to guide prognosis on the basis of clinical features present at diagnosis.
A total of 181 patients with G1D were included in the study (92 [50.8%] male and 89 female [49.2%]; median age, 9 years; age range, 0-65 years). As previously known, a relatively large variety of common phenotypes are characteristic of the G1D syndrome, including movement disorders, absence epilepsy (typical and atypical), and myoclonic and generalized epilepsies. The 3 main novel results are (1) the feasibility of effective dietary therapies (such as the modified Atkins diet) other than the ketogenic diet, (2) the relatively frequent occurrence (one-fourth of cases) of white matter magnetic resonance imaging abnormalities, and (3) the favorable effect of early diagnosis and treatment regardless of treatment modality and mutation type. In fact, the most important factor that determines outcome is age at diagnosis, as reflected in a predictive mathematical model.
The results reveal several changing notions in the approach to G1D syndrome diagnosis and treatment, such as the perceived absolute requirement for a ketogenic diet, the assumed lack of structural brain defects, and the potential existence of genotype-phenotype correlations, all of which are contested by the registry data.
病例报告经常记录1型葡萄糖转运体缺乏症（G1D）的独特或不寻常方面。相比之下，缺乏可供进行全球推断的人群研究。最早的病例报告发布25年后，这种缺乏症仍然对治疗和预后咨询产生特别影响。
研究G1D最常见的特征。
设计、背景和参与者：在本研究中，2013年12月1日至2016年12月1日期间，通过一个基于网络的全球患者登记处，以电子方式收集了181例G1D患者的数据。该研究使用了几种统计方法，专门用于处理各种形式G1D的发病年龄、相关表现、自然病史、治疗效果和诊断程序。这些因素在一个预测性数学模型中相互关联，该模型旨在根据诊断时存在的临床特征指导预后。
本研究共纳入181例G1D患者（男性92例[50.8%]，女性89例[49.2%]；中位年龄9岁；年龄范围0 - 65岁）。如前所述，G1D综合征具有相对多样的常见表型特征，包括运动障碍、失神癫痫（典型和非典型）以及肌阵挛性癫痫和全身性癫痫。三个主要的新发现是：（1）除生酮饮食外，有效饮食疗法（如改良阿特金斯饮食）的可行性；（2）白质磁共振成像异常相对频繁出现（四分之一的病例）；（3）无论治疗方式和突变类型如何，早期诊断和治疗均有良好效果。实际上，预测性数学模型显示，决定预后的最重要因素是诊断时的年龄。
研究结果揭示了G1D综合征诊断和治疗方法中几个不断变化的观念，如生酮饮食被认为是绝对必要的、假定不存在脑结构缺陷以及潜在的基因型 - 表型相关性，而登记数据均对这些观念提出了质疑。
