本报告概述了一例儿童患有一种先天性糖基化疾病(CDG),称为ALG2-CDG(OMIM607906)。表现为由ALG2中鉴定的变体引起的先天性肌无力综合征(CMS),其编码参与N-糖基化早期步骤的α1,3-甘露糖基转移酶(EC2.4.1.132)。迄今为止,14例ALG2-CDG已在世界范围内记录。从出生,这个孩子经历了围产期窒息,肌肉无力,进食困难与没有吸吮反射有关,先天性髋关节脱位,和低张力。随着时间的推移,出现了额外的并发症,如吸气喘鸣,胃食管反流,低摄入量,反复发作,呼吸道感染,无法保持头部直立,和全球发展延迟。全基因组测序(WGS)揭示了复合杂合性中存在两个ALG2变体:一个新的变体c.1055_1056delinsTGAp。(Ser352Leufs*3)和一个不确定意义的变体(VUS)c.964C>Ap。(Pro322Thr)。其他研究,包括碳水化合物缺乏的转铁蛋白(CDT)的测定,显示出轻度的I型CDG模式和异常的转铁蛋白糖型的存在,其中包含由一种唾液酸组成的线性七糖,一个半乳糖,一种N-乙酰氨基葡萄糖,两种甘露糖和两种N-乙酰葡糖胺(NeuAc-Gal-GlcNAc-Man2-GlcNAc2),ALG2-CDG诊断生物标志物,证实这些变异的致病性。
This report outlines the case of a child affected by a type of congenital disorder of glycosylation (CDG) known as ALG2-CDG (OMIM 607906), presenting as a congenital myasthenic syndrome (CMS) caused by variants identified in ALG2, which encodes an α1,3-mannosyltransferase (EC 2.4.1.132) involved in the early steps of N-glycosylation. To date, fourteen cases of ALG2-CDG have been documented worldwide. From birth, the child experienced perinatal asphyxia, muscular weakness, feeding difficulties linked to an absence of the sucking reflex, congenital hip dislocation, and hypotonia. Over time, additional complications emerged, such as inspiratory stridor, gastroesophageal reflux, low intake, recurrent seizures, respiratory infections, an inability to maintain the head upright, and a global developmental delay. Whole genome sequencing (WGS) revealed the presence of two ALG2 variants in compound heterozygosity: a novel variant c.1055_1056delinsTGA p.(Ser352Leufs*3) and a variant of uncertain significance (VUS) c.964C>A p.(Pro322Thr). Additional studies, including determination of carbohydrate-deficient transferrin (CDT) revealed a mild type I CDG pattern and the presence of an abnormal transferrin glycoform containing a linear heptasaccharide consisting of one sialic acid, one galactose, one N-acetyl-glucosamine, two mannoses and two N-acetylglucosamines (NeuAc-Gal-GlcNAc-Man2-GlcNAc2), ALG2-CDG diagnostic biomarker, confirming the pathogenicity of these variants.