Gaucher disease is a
sphingolipid storage disorder caused by a deficiency of the lysosomal
enzyme glucocerebrosidase (GC) and the consequent deposition of
glucocerebrosides into the cells of the macrophagic system. Among the three types of clinical disease, type 1 leads to hepatosplenomegaly,
hypersplenism and skeletal abnormalities including bone
pain,
osteopenia and fractures. Two pediatric female patients with moderately severe
type 1 Gaucher disease were treated with commercially available GC,
mannose terminated to be macrophage-targeted. GC was given by
intravenous infusion (30 to 60 units per kilogram of
body weight every two weeks) for 8 and 18 months. The
hemoglobin concentration increased and the serum
acid phosphatase decreased in both patients. In the most affected child, hepatic volume decreased significantly and bony symptoms disappeared. Infusions were uneventful except for an episode of
anaphylaxis that subsided rapidly, allowed resumption and did not affect efficacy. These observations are in agreement with the international experience in approximately 800 cases, with good tolerance in all type 1 patients who show objective clinical improvement; patterns of response are variable from patient to patient, independent from previous
splenectomy, and dose-dependent; the dose can be tapered after a period of time.
Antibodies anti-GC are seen in 13% of the patients, but 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.