DIFFERENTIAL-EFFECTS OF ENZYME SUPPLEMENTATION THERAPY ON MANIFESTATIONS OF TYPE-1 GAUCHER-DISEASE

BACKGROUND: In type 1 Gaucher disease (GD), the accumulation of glucoc erebroside in macrophages, caused by deficient activity of glucocerebr osidase, results in a variety of disease manifestations. In addition t o the characteristic features of hepatosplenomegaly, cytopenia, and bo ne abnormalities, resting energy expenditure (REE) and glucose product ion are increased. In this study the effects of enzyme supplementation therapy on metabolic parameters in relation to other disease manifest ations in type 1 GD patients are investigated. PATIENTS AND METHODS: I n 12 adult type 1 GD patients, measurements of REE (by indirect calori metry), liver and spleen volume (by spiral computerized axial tomograp hy [CT]) and hemoglobin and platelet count were obtained before and af ter 6 months of alglucerase therapy (15 U/kg per month). In 7 of the 1 2 patients hepatic glucose production was measured by infusing 3-H-3 g lucose. For comparison, REE and glucose metabolism were studied in 7 w eight- and age-matched healthy subjects. RESULTS: REE and glucose prod uction were increased in GD patients as compared with controls (REE: 2 9.8 kcal/kg/24 h +/- 3.6 and 23.1 +/- 2.3 kcal/kg/24 h, respectively, P < 0.05; glucose production: 14.00 mu mol/kg/min +/- 0.51 and 10.77 m u mol/kg/min +/- 0.26, respectively, P < 0.03). There were no differen ces in plasma glucose concentrations. Whereas the elevated REE decreas ed after 6 months of alglucerase therapy from 129% to 120% of predicte d values (P < 0.01), the increase in hepatic glucose production did no t change. An increase in weight occurred after 6 months of treatment ( 1.7 +/- 0.8 kg, P < 0.001), which was accounted for by an increase in fat mass of 1.6 +/- 1.5 kg (P < 0.02). Hemoglobin levels increased fro m 11.2 mg/dL to 12.1 mg/dL (P = 0.05) and platelet counts rose from 84 x 10(9)/L to 113 x 10(9)/L (P < 0.05). Although liver and spleen volu mes decreased by similar to 10% and similar to 20%, respectively, ther e was no correlation between the decrease in organ volumes and the dec rease in REE. CONCLUSIONS: Treatment with alglucerase improves hyperme tabolism and organomegaly in GD, whereas the increase in glucose produ ction persists. Therefore, the dose-response effects of alglucerase ar e variable for the different manifestations of type 1 GD. (C) 1997 by Excerpta Medica, Inc.