Decreased plasma concentration of von Willebrand factor antigen (VWF:Ag) in patients with glycogen storage disease type Ia

Abstract

Despite highly increased blood lipids, patients with glycogen storage disease type Ia (GSD Ia) do not develop premature vascular complications. Since this could be due to changes of coagulation factors, coagulation tests (including von Willebrand factor (VWF) antigen (VWF:Ag) ELISA, VWF:collagen binding activity (VWF:CB) and VWF multimer analysis) were performed in 10 GSD Ia patients, single cases of other GSD types, and in both healthy and hyperlipidaemic controls. In 60% of GSD Ia patients we found abnormal results, with a decrease of VWF:Ag and multimer analysis showing reduced intensity of individual oligomers in the presence of all multimers with a normal triplet structure. We interpret these findings as an acquired 'von Willebrand syndrome type I' in GSD Ia. The underlying metabolic mechanism and a potential role in the protection from vascular complication still needs to be evaluated.

Diagnosis and management of glycogen storage disease type I: a practice guideline of the American College of Medical Genetics and Genomics

“…[22][23][24][25][26] GSD I has been associated with a bleeding diathesis due to impaired platelet function 27 and/or a von Willebrand-like platelet defect. 28 Anemia is also noted, especially in patients with hepatic adenomas. 29 Vitamin D deficiency is increasingly recognized in these patients.…”

Fertility and pregnancy in women affected by glycogen storage disease type I, results of a multicenter Italian study

“…Bleeding tendency, due to platelet dysfunction and defect of von Willebrand factor (Mühlhausen et al 2005), can potentially cause hemorrhagic problems during gestation and especially during delivery in GSD I patients. Nevertheless, no bleeding diathesis has been seen in our cohort, nor in the pregnancies reported in the literature so far.…”

Vascular Dysfunction in Glycogen Storage Disease Type I

“…The concept of decreased platelet aggregation in the study by Muhlhausen et al 7 was based on evidence of a relative von Willebrand deficiency. Patients were noted to have a bleeding diathesis, and von Willebrand levels were lower than population norms.…”

“…Given these observations, several mechanisms have been postulated to be protective against heart disease, including reverse cholesterol transport, increased antioxidant potential, or decreased platelet aggregation. 5–7 …”