ENZYME REPLACEMENT THERAPY IN GAUCHER DIS EASE TYPE-1

Gaucher disease is a sphingolipid storage disorder caused by a deficie ncy of the lysosomal enzyme glucocerebrosidase (GC) and the consequent deposition of glucocerebrosides into the cells of the macrophagic sys tem. Among the three types of clinical disease, type 1 leads to hepato splenomegaly, hypersplenism and skeletal abnormalities including bone pain, osteopenia and fractures. Two pediatric female patients with mod erately severe type 1 Gaucher disease were treated with commercially a vailable GC, mannose terminated to be macrophage-targeted. GC was give n by intravenous infusion (30 to 60 units per kilogram of body weight every two weeks) for 8 and 18 months. The hemoglobin concentration inc reased and the serum acid phosphatase decreased in both patients. In t he most affected child, hepatic volume decreased significantly and bon y symptoms disappeared. Infusions were uneventful except for an episod e of anaphylaxis that subsided rapidly, allowed resumption and did not affect efficacy. These observations are in agreement with the interna tional experience in approximately 800 cases, with good tolerance in a ll type 1 patients who show objective clinical improvement; patterns o f response are variable from patient to patient, independent from prev ious splenectomy, and dose-dependent; the dose can be tapered after a period of time. Antibodies anti-GC are seen in 13% of the patients, bu t their presence does not have clinical consequences. The cost of the enzyme makes it crucial to define precise indications, optimal dosing schedules, duration of treatment and cost-benefit ratio.