Increased levels of hemostatic proteins are independent of inflammation in glycogen storage disease type Ia.
OBJECTIVE
Glycogen storage disease type Ia (GSD-Ia), a congenital deficiency of hepatic glucose-6-phosphatase activity, is often associated with hyperproteinemia. To document the mechanism of hyperproteinemia, the proteins of the hemostatic system were analyzed according to their site of synthesis: hepatocyte, endothelial cell, or both. The role of inflammation was investigated by the measurement of tumor necrosis factor alpha (TNF-alpha) and interleukin-6 (IL-6) levels in plasma.


METHODS
Twenty-seven patients with GSD-Ia were evaluated, as were 14 patients with other types of GSD and 30 healthy control subjects. Of the 41 patients with GSD, 15 also had hepatic adenoma (14 patients with GSD-Ia and 1 with GSD type III).


RESULTS
In patients with GSD-Ia, there was a two-fold increase in all hepatocyte-synthesized proteins (i.e., factor VII, protein C, C4b binding protein) compared with control subjects and patients with other types of GSD. The proteins with mixed endothelial and hepatocyte origin (i.e., antithrombin and protein S) also were significantly increased but to a lesser extent. In contrast, the mean concentration of von Willebrand factor, which is exclusively synthesized in endothelial cells, was normal, as was the concentration of TNF-alpha and IL-6.


CONCLUSIONS
These results suggest that the hyperproteinemia of GSD-Ia (including hemostatic proteins) is attributable to hepatocyte dysfunction and not related to an inflammatory process.
Marfaing-Koka
Anne
A
Service d'Hématologie Biologique, Hôpital Antoine Béclère, Clamart, France.
Wolf
Martine
M
Boyer-Neumann
Catherine
C
Meyer
Dominique
D
Odievre
Michel
M
Labrune
Philippe
P
D000293:Adolescent; D000328:Adult; D000991:Antithrombins / Q000032:analysis; D001798:Blood Proteins / Q000032:analysis*; D002648:Child; D002675:Child, Preschool; D003169:Complement Inactivator Proteins; D042783:Endothelial Cells / Q000378:metabolism; D005167:Factor VII / Q000032:analysis; D005953:Glycogen Storage Disease Type I / Q000097:blood*; D006023:Glycoproteins / Q000097:blood; D006487:Hemostasis; D006801:Humans; D007249:Inflammation / Q000097:blood*; D015850:Interleukin-6 / Q000032:analysis; D008099:Liver / Q000378:metabolism; D017395:Plasminogen Activator Inhibitor 1 / Q000097:blood; D011486:Protein C / Q000032:analysis; D017293:Protein S / Q000032:analysis; D014280:Triglycerides / Q000097:blood; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis; D014841:von Willebrand Factor / Q000032:analysis
D000991:Antithrombins; D001798:Blood Proteins; D003169:Complement Inactivator Proteins; D006023:Glycoproteins; D015850:Interleukin-6; D017395:Plasminogen Activator Inhibitor 1; D011486:Protein C; D017293:Protein S; D014280:Triglycerides; D014409:Tumor Necrosis Factor-alpha; D014841:von Willebrand Factor; D005167:Factor VII