GSD Ia Patients Research Articles

65 HEXOSEMONOPHOSPHATE (HMP) SHUNT ACTIVITY AND GLUCOSE TRANSPORT IN POLYMORPHONUCLEAR (PMNL) AND LYMPHOCYTE CELLS OF PATIENTS WITH GLYCOGENOSIS (GSD) I

GSD I is characterized by deficiency of liver glucose-6-phosphatase (Ia) or of a microsomal transporter for G6P (Ib). Both variants present with similar clinical features; however, GSD Ib patients suffer from neutropenia and impaired functions of their PMNL cells. This study measures HMP shunt activity and glucose transport in PMNL cells and lymphocytes of patients with GSD la and Ib, as well as of controls. The HMP shunt activity decreased significantly in intact PMNL cells of GSD Ib patients as compared to GSD Ia patients and to controls (Ib: 15.5±2.5, la: 47, control: 44.7±5.0 nmole/mg prot/h; P control:Ib<0.001). The reduced HMP shunt activity rose to above normal levels in disrupted GSD Ib PMNL cells (Ib: 117±18, control 75±10; P<0.005). HMP shunt activity of intact lymphocytes was the same in all 3 groups studied. The rate of deoxyglucose transport into GSD Ib PMNL cells was 30% of normal (0.86±0.38 as compared to control of 3.1±0.7 nmole/mg prot/min). This abnormal transport was present neither in GSD Ib lymphocytes nor in GSD Ia PMNL cells and lymphocytes. The striking limitation of glucose transport via the cell membrane of PMNL cells of GSD Ib patients can account for the impairment of leucocyte function which is characteristic of GSD Ib but not found in GSD Ia.

DDAVP infusion in five patients with type Ia glycogen storage disease and associated correction of prolonged bleeding times

Five patients with glycogen storage disease type I (GSD-I) were evaluated for a bleeding diathesis and subsequently were given an infusion of 1-deamino-8-D-arginine vasopressin (DDAVP). Although platelet counts were normal or slightly elevated, the baseline template bleeding times were prolonged in four of the patients. Prothrombin times and activated partial thromboplastin times were normal, while ADP- and epinephrine-induced platelet aggregations were absent in the three patients tested. Ristocetin- and collagen-induced platelet aggregations were abnormal. Laurell and immunoradiometric determinations of the factor VIII-related antigen (vWf antigen) were decreased. Glyoxyl agarose gel electrophoresis of the patients' plasma revealed abnormal multimer patterns in four of the five patients. After the DDAVP infusion the platelet aggregation abnormalities persisted; however, the bleeding time and the von Willebrand antigen and activity corrected. We conclude that GSD-Ia patients may have a metabolically acquired form of von Willebrand's syndrome as well as an acquired intrinsic platelet defect, and that DDAVP may be useful in the management of bleeding in these patients.

DDAVP Infusion in Five Patients With Type Ia Glycogen Storage Disease and Associated Correction of Prolonged Bleeding Times

Five patients with glycogen storage disease type I (GSD-I) were evaluated for a bleeding diathesis and subsequently were given an infusion of 1-deamino-8-D-arginine vasopressin (DDAVP). Although platelet counts were normal or slightly elevated, the baseline template bleeding times were prolonged in four of the patients. Prothrombin times and activated partial thromboplastin times were normal, while ADP- and epinephrine-induced platelet aggregations were absent in the three patients tested. Ristocetin- and collagen-induced platelet aggregations were abnormal. Laurell and immunoradiometric determinations of the factor VIII-related antigen (vWf antigen) were decreased. Glyoxyl agarose gel electrophoresis of the patients' plasma revealed abnormal multimer patterns in four of the five patients. After the DDAVP infusion the platelet aggregation abnormalities persisted; however, the bleeding time and the von Willebrand antigen and activity corrected. We conclude that GSD-Ia patients may have a metabolically acquired form of von Willebrand's syndrome as well as an acquired intrinsic platelet defect, and that DDAVP may be useful in the management of bleeding in these patients.