GSD Ib Research Articles

Improvement of neutropenia and neutrophil dysfunction by granulocyte colony-stimulating factor in a patient with glycogen storage disease type Ib

Patients with glycogen storage disease type Ib (GSD Ib) suffer from recurrent bacterial infections due to neutropenia and neutrophil dysfunction. To improve the quality of life in a 9-year-old boy with GSD Ib, we subcutaneously administered recombinant human granulocyte colony-stimulating factor (G-CSF). Daily injections of 100 micrograms/m2 of G-CSF significantly increased absolute neutrophil counts and augmented neutrophil mobility. The patient was then treated with 70 and 100 micrograms/m2 of G-CSF daily and twice-weekly. The treatment maintained absolute neutrophil counts at significantly higher levels than those without treatment for 22 months and markedly decreased the frequency of infections and the necessity for hospitalisation. Weekly injections of 70 micrograms/m2 of G-CSF were less efficient. No adverse effects were observed during treatment. These findings indicate that daily and twice-weekly treatment with G-CSF of long duration are safe and effective for patients with GSD Ib. G-CSF may be a useful therapeutic agent in patients with neutrophilic impairment as a consequence of a metabolic disorder.

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.

Glycogen storage disease type Ib: familial bleeding tendency.

A mild bleeding tendency with characteristics of the von Willebrand disease was documented in family members of a girl with glycogen storage disease type Ib (GSD) Ib). It was assumed that a defective glucose-6-phosphate dependent microsomal glycoprotein synthesis was involved in the bleeding disorder of the patient and the GSD Ib heterozygotes.