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Clinical and biochemical presentation of siblings with COG‐7 deficiency, a lethal multiple O‐ and N‐glycosylation disorder
Author(s) -
Spaapen L. J. M.,
Bakker J. A.,
der Meer S. B.,
Sijstermans H. J.,
Steet R. A.,
Wevers R. A.,
Jaeken J.
Publication year - 2005
Publication title -
journal of inherited metabolic disease
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.462
H-Index - 102
eISSN - 1573-2665
pISSN - 0141-8955
DOI - 10.1007/s10545-005-0015-z
Subject(s) - glycosylation , glycoprotein , golgi apparatus , sialic acid , protein subunit , isoelectric focusing , biology , apolipoprotein b , mucolipidosis , haptoglobin , biochemistry , gene isoform , threonine , endocrinology , enzyme , gene , serine , endoplasmic reticulum , cholesterol
Summary Congenital disorders of glycosylation (CDG) represent a group of inherited multiorgan diseases caused by defects in the biosynthesis of glycoproteins. We report on two dysmorphic siblings with severe liver disease who died at the age of a few weeks. Increased activities of lysosomal enzymes in plasma were found, though total sialic acid in plasma was strongly decreased. Isoelectric focusing of serum sialotransferrins showed a type 2‐like CDG pattern. Some of the known CDG subtypes were excluded. O‐Glycosylation was investigated by isoelectric focusing of apolipoprotein C‐III, which showed increased fractions of hyposialylated isoforms. In a consecutive study a defect in the conserved oligomeric Golgi complex was established at the level of subunit COG‐7, leading to disruption of multiple glycosylation functions of the Golgi. This report on patients with a new variant of CDG, due to a multiple Golgi defect, emphasizes in addition to sialotransferrins the importance of analysis of a serum O‐linked glycoprotein, e.g. apolipoprotein C‐III, in unclassified CDG‐X cases.