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

Abstract

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.