Faculty of Medicine, Department of Metabolic Diseases, Gazi University, Ankara, Turkey.
Faculty of Medicine, Department of Pediatric Neurology, Gazi University, Ankara, Turkey.
Am J Med Genet A. 2021 Sep;185(9):2739-2747. doi: 10.1002/ajmg.a.62247. Epub 2021 May 7.
The pathophysiology of congenital defects of glycosylation (CDG) is complex and the diagnosis has been a challenge because of the overlapping clinical signs and symptoms as well as a large number of disorders. Isoelectric focusing of transferrin has been used as a screening method but has limitations. Individual enzyme or molecular genetic tests have been difficult to perform. In this study, we aimed to describe CDG patients who were referred to from different departments either without a preliminary diagnosis or suspected to have a genetic disorder other than CDG. The patients were diagnosed mainly with a 450 gene next-generation DNA sequencing panel for inborn errors of metabolism, which also included 25 genes for CDG. A total of 862 patients were investigated with the panel, whereby homozygous (10) or compound heterozygous (4) mutations were found in a total of 14 (1.6%) patients. A total of 13 different mutations were discovered, 10 of them being novel. Interestingly, none of the patients was suspected to have a CDG before referral. This report expands the clinical/laboratory findings in patients with CDG and stresses on the fact that CDG should be in the differential list for pediatric patients presented with nonspecific dysmorphic features and neurological delays/regression. Also, next-generation DNA sequencing with panel approach was noticed to have a significant diagnostic potential in patients presented with nonspecific neurologic and dysmorphic findings.
先天性糖基化缺陷（CDG）的病理生理学较为复杂，由于临床表现和症状重叠，以及大量疾病的存在，其诊断一直具有挑战性。转铁蛋白等电聚焦已被用作筛选方法，但存在局限性。个别酶或分子遗传学检测一直难以进行。在这项研究中，我们旨在描述从不同科室转来的 CDG 患者，他们要么没有初步诊断，要么疑似患有除 CDG 以外的遗传疾病。这些患者主要通过用于代谢性遗传病的 450 个基因新一代 DNA 测序面板进行诊断，其中还包括 25 个 CDG 基因。共有 862 名患者接受了该面板的检查，其中共有 14 名（1.6%）患者存在纯合子（10 名）或复合杂合子（4 名）突变。共发现 13 种不同的突变，其中 10 种为新发现。有趣的是，在转诊之前，没有患者被怀疑患有 CDG。本报告扩展了 CDG 患者的临床/实验室发现，并强调了一个事实，即 CDG 应列入具有非特异性发育不良特征和神经发育迟缓/退行性改变的儿科患者的鉴别诊断清单中。此外，对于具有非特异性神经和发育不良表现的患者，采用新一代 DNA 测序和面板方法具有显著的诊断潜力。
