Clinical and biochemical presentation of siblings with COG‐7 deficiency, a lethal multiple O‐ and N‐glycosylation disorder

Journal of Inherited Metabolic Disease - Tập 28 Số 5 - Trang 707-714 - 2005
L. J. M. Spaapen1,2, Jaap Bakker1, Suzanne van Meer3, H. J. Sijstermans3, Richard Steet4, Ron A. Wevers5, J. Jaeken6
1Department of Biochemical Genetics, Academic Hospital Maastricht, Heerlen, The Netherlands
2Department of Biochemical Genetics, Academic Hospital Maastricht, PO Box 5800, AZ Maastricht, 6202 The Netherlands
3Department of Pediatrics, Atrium Medisch Centrum, Heerlen, The Netherlands
4Department of Internal Medicine, Washington University School of Medicine, Saint Louis, Missouri, USA
5Laboratory of Pediatrics and Neurology, University Medical Center, Nijmegen, The Netherlands
6Center for Metabolic Diseases, Universitair Ziekenhuis Gasthuisberg, Leuven, Belgium

Tóm tắt

SummaryCongenital 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.

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Journal of Inherited Metabolic Disease

Tập 28 Số 5

707-714

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