Congenital disorder of glycosylation IId (CDG-IId) -: A new entity:: Clinical presentation with Dandy-Walker malformation and myopathy
Congenital disorder of glycosylation IId (CDG-IId) -: A new entity:: Clinical presentation with Dandy-Walker malformation and myopathy
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DOI：
10.1055/s-2002-23597
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发表时间：
2002-02-01
期刊：
影响因子：
1.4
通讯作者：
Heidemann, PH
中科院分区：
文献类型：
--
作者：
Peters, V;Penzien, JM;Heidemann, PH
1例1.5岁男孩因Dandy-Walker畸形导致的大头畸形，表现为进行性脑积水、广泛肌张力减退、一过性胆汁淤积综合征、广泛凝血异常和肌酸激酶升高，提示肌病。诊断性检查表明存在先天性糖基化障碍（CDG，以前称为碳水化合物缺乏糖蛋白综合征）。通过自动等电聚焦（IEF）获得的血清转铁蛋白模式显示了迄今为止未报道的模式，强烈升高的三，二，单和asialotransferrin带，增加在这个顺序一起显着降低tetrasialotransferrin。对另外两种糖蛋白α（1）-抗胰蛋白酶和α（1）-抗胰凝乳蛋白酶的研究证实了糖基化的普遍缺陷。所有已知的糖基化缺陷都可以通过白细胞或成纤维细胞中的酶分析或IEF获得的结果排除。SDS-电泳证明转铁蛋白的分子量有显着差异，表明缺乏部分或全部寡糖链。该缺陷可描述为由于纯合插入（1031-1032 insC）导致的β-1，4-半乳糖基转移酶（E.C.2.4.1.38）缺陷。生物化学和分子学研究结果的细节将在别处描述。
A 1.5-year-old boy with macrocephaly due to a Dandy-Walker malformation presented with progressive hydrocephalus, extensive muscular hypotonia, transient cholestatic syndrome, extensive coagulation abnormalities and elevated creatine kinase indicating myopathy. Diagnostic work-up indicated a congenital disorder of glycosylation (CDG, formerly carbohydrate deficient glycoprotein syndrome). The serum transferrin pattern obtained by automated isoelectric focusing (IEF) showed an hitherto unreported pattern with strongly elevated tri-, di-, mono- and asialotransferrin bands, increasing in this order together with markedly decreased tetrasialotransferrin. Investigation of two additional glycoproteins, alpha(1)-antitrypsin and alpha(1)-antichymotrypsin, confirmed a generalised defect of glycosylation. All known glycosylation defects could be ruled out by enzymatic analyses in either leukocytes or fibroblasts or by the results obtained by IEF. SDS-electrophoresis demonstrated a marked difference in the molecular weight of transferrin, suggesting the lack of parts or of all oligosaccharide chains. The defect could be delineated to a deficiency of beta-1,4-galactosyltransferase (E.C.2.4.1.38) due to a homozygous insertion (1031-1032 insC). Details of the biochemical and molecular findings will be described elsewhere.