Clinical Heterogenity in Patients with Congenital Disorders of Glycosylation

先天性糖基化异常是一组多种多样的代谢紊乱，表现为一系列的临床特征，从严重的神经系统表现和多系统受累到低血糖和发育正常的严重胃肠道症状。现在有17种类型的CDG由不同的酶缺陷和基因定义，这些基因都与N-连接的寡糖的合成有关。在美国，被诊断为CDG的儿童和成人的数量正在迅速增加，表型的差异也更大。很明显，这些疾病的临床表型和并发症正在扩大。我们正计划在这些研究中纳入一组新的称为先天性肌营养不良(CMD)的疾病。这些疾病的潜在代谢基础是甘露糖型O-连接低聚糖的异常合成。随着对患者表型的研究，这两种疾病都有类似的临床问题可以得到回答。即将到来的一年的目标将是继续识别和评估患有CDG和CMD的个体患者，探索非分型个体的临床和生化特征，并通过临床研究，继续增加医生照顾这些受影响的成人和儿童的临床管理策略纲要。我们已经在GeneReviews上完成了一项受邀的审查，这是一个为治疗罕见遗传病患者的医生提供的在线资源。

Congenital Disorders of Glycosylation are a diverse group of metabolic disorders presenting with a spectrum of clinical features ranging from severe neurologic manifestations and multisystemic involvement to hypoglycemia and severe gastrointestinal symptoms with normal development. There are now 17 types of CDG defined by distinct enzyme defects and genes all involved in the synthesis of N-linked oligosaccharides. The number of children and adults diagnosed with CDG in the United States is increasing rapidly with a wider variance in the phenotypes. It is clear that the clinical phenotypes and complications of these disorders are expanding. We are planning to include in these studies a new group of disorders called Congenital Muscular Dystophies(CMD). The underlying metabolic bases of these disorders is the abnormal synthesis of O-linked oligosaccharide of the mannose type. There are similar clinical questions in both of these disorders that can be answered as patient phenotypes are studied. The goal of the upcoming year will be to continue to identify and evaluate individual patients with CDG and CMD, to explore the clinical and biochemical features of untyped individuals and, through clinical research, continue to add to the compendium of clinical management strategies for physicians caring for these affected adults and children. We have completed an invited review in GeneReviews, an online resource for physicians caring for individuals with rare genetic disorders.