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Hemostatic studies in patients with carbohydrate-deficient glycoprotein syndrome
K Iijima1, F Murakami, K Nakamura
1Department of Clinical Laboratory, Tottori University Hospital, Yonago, Japan.
Insights
Carbohydrate deficient glycoprotein (CDG) syndrome patients exhibit reduced coagulation inhibitors like antithrombin III due to impaired glycosylation. This deficiency increases the risk of thrombotic events in individuals with CDG syndrome.
Area of Science:
- Biochemistry
- Hematology
- Genetics
Background:
- Carbohydrate deficient glycoprotein (CDG) syndrome is a genetic disorder affecting protein glycosylation.
- Patients often experience transient stroke-like episodes.
- Hemostatic abnormalities are suspected but not well-characterized.
Purpose of the Study:
- To investigate hemostatic profiles in CDG syndrome patients.
- To determine the role of coagulation inhibitors in thrombotic events associated with CDG syndrome.
Main Methods:
- Hemostatic studies were conducted on three CDG syndrome patients from two families.
- Plasma levels of antithrombin III (AT III), protein C, protein S, and alpha 2 plasmin inhibitor were measured.
- Isoelectric focusing was used to analyze antithrombin III structure.
Main Results:
- Significantly reduced levels of AT III, protein C, and alpha 2 plasmin inhibitor were observed (approx. 50% of normal).
- Protein S was reduced in two sibling patients.
- Isoelectric focusing revealed altered AT III glycosylation, with a minor band lacking an oligosaccharide sidechain.
- One patient developed disseminated intravascular coagulation and arterial thrombosis.
Conclusions:
- CDG syndrome is associated with decreased levels of key coagulation inhibitors.
- Impaired glycosylation of AT III is a likely cause of thrombotic predisposition in CDG syndrome.
- These findings highlight the importance of hemostatic monitoring in CDG syndrome patients.
Abstract:
The carbohydrate deficient glycoprotein (CDG) syndrome is a newly described disorder characterized by impaired glycosylated molecules. It has been reported that transient stroke-like episodes appear in half of the patients. We performed hemostatic studies on three CDG syndrome patients belonging to two unrelated families. The most characteristic findings were decreases in antithrombin III (AT III), protein C and alpha 2 plasmin inhibitor to nearly half normal levels. Protein S was reduced in two (siblings) patients. Isoelectric focusing of AT III in native plasma revealed decreased intensity of the major band and increased intensity of a minor cathodal band. These minor AT III molecules were considered to lack an oligosaccharide sidechain. A 12-year-old girl defective not only for AT III but also protein C and protein S developed disseminated intravascular coagulation accompanied by arterial thrombosis in her left hand following dyspnea associated with bronchial asthma. These findings suggest that thrombotic predisposition in patients with CDG syndrome is due to decreased levels of major coagulation inhibitors, particularly as a result of impaired glycosylation of AT III.