Cryptogenic liver disease in four children: A novel congenital disorder of glycosylation
Cryptogenic liver disease in four children: A novel congenital disorder of glycosylation
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DOI：
10.1203/01.pdr.0000196378.30165.26
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发表时间：
2006-02-01
影响因子：
3.6
通讯作者：
Vajro, P
中科院分区：
文献类型：
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作者：
Mandato, C;Brive, LE;Vajro, P
我们调查了四名儿童的代谢缺陷，他们表现为孤立的隐源性慢性肝病、凝血功能障碍和几种无关的血清糖蛋白异常。对患者血清糖蛋白和成纤维细胞的分析表明，他们有一个新的先天性糖基化障碍（CDG）。所有患者的转铁蛋白（Tf）等电聚焦（IEF）图谱均异常。通过电喷雾电离质谱法（ESI-MS）对Tf进行的更详细的分析显示过多的异常糖基化，包括1-2个唾液酸和1-2个半乳糖单位的损失，这是典型的II组缺陷。两名患者的转铁蛋白也缺乏1-2个完整的寡糖链，这是第一组疾病的典型特征。通过HPLC和基质辅助激光解吸/电离质谱法分析血清总N-聚糖，也显示缺乏唾液酸和半乳糖单元的中性聚糖链比例增加。分析患者成纤维细胞通过CDG-Ih、-IL和CDG-IId消除CDG-1a。我们的研究结果表明，如果临床上无症状，隐源性高转氨酶血症和/或肝脂肪纤维化的儿童亚组可能代表一种新类型的CDG-X与所有未知的缺陷（S）。鼓励临床医生通过ESI-MS检测此类患者的异常Tf糖基化。
We investigated the metabolic defect(s) Of four Children who presented with isolated cryptogenic chronic liver disease, coagulopathy, and abnormalities of several unrelated serum glycoproteins. Analysis of the patients' serum glycoproteins and fibroblasts suggest they have it novel congenital disorder of glycosylation (CDG). All had abnormal transferrin (Tf) isoelectric focusing (IEF) profiles. More detailed analysis of Tf by electrospray ionization mass spectrometry (ESI-MS) showed a plethora of abnormal glycosylations that included loss of 1-2 sialic acids and 1-2 galactose Units, typical of Group II defects. Tf from two patients also lacked 1-2 entire oligosaccharide chains, typical of Group One disorders. Total serum N-glycans were analyzed by HPLC and matrix-assisted laser desorption/ionization mass spectrometry and also showed increased proportion of neutral glycan Chains lacking sialic acids and galactose units. Analysis of patient fibroblasts eliminated CDG-1a, through CDG-Ih, -IL and CDG-IId. Our results suggest that if Subset of children with clinically asymptomatic, cryptogenic hypertransaminasemia and/or liver steato-fibrosis may represent a novel type of CDG-X with ail unknown defect(s). Clinicians are encouraged to test such patients for abnormal Tf glycosylation by ESI-MS.