Lower-dose, high-frequency enzyme replacement therapy in children with type 1 Gaucher disease: Experience at the Schneider Children's Medical Center of Israel

Individuals with more severe type 1 Gaucher disease usually are diagnosed as children. These patients frequently present with marked hematologic and visceral signs and symptoms, serious skeletal complications, growth retardation, and delayed puberty. Enzyme replacement therapy (ERT) with alglucerase (Ceredase®; Genzyme Corporation, Cambridge, MA) in a dosage of 60 U/kg every 2 weeks has achieved hematologic and visceral responses and reversed growth stunting, pubertal delay, and some skeletal abnormalities. A lower-dose, high-frequency regimen of 2.3 U/kg three times weekly has produced satisfactory hematologic and hepatosplenic responses. The National Committee of the Israeli Medical Health Insurance Funds has established formal eligibility criteria for ERT. Cost considerations limit treatment to patients with more severe disease and to the use of the lower-dose, high- frequency ERT regimen. Eighteen children evaluated at the Schneider Children's Medical Center of Israel currently are receiving alglucerase (n = 13) or the recombinant enzyme, imiglucerase (n = 5) (Cerezyme(TM); Genzyme Corporation), in a dosage of 2.3 U/kg three times weekly. All 18 patients are compound heterozygotes with one N370S (1226G) allele, genotypes usually associated with early onset of disease and severe signs and symptoms. Accordingly, these patients presented at a very early age, generally with marked signs and symptoms of type 1 Gaucher disease, including splenomegaly in patients with intact or partially intact spleens, hepatomegaly, and decreased hemoglobin levels and platelet counts. Serum levels of tartrate- resistant acid phosphatase (TRAP), a biochemical marker of Gaucher disease, were elevated in all patients. Severe skeletal disease (osteonecrosis and bone crisis) was present in all patients, and seven children suffered from growth retardation. The 13 patients who have received alglucerase for 1 to 3.5 years (mean, 2.25) have been evaluated, and results are presented in this report. Hepatosplenomegaly improved in all affected children. In the majority of patients hemoglobin levels and platelet counts increased, and in all but one patient TRAP levels decreased. Although nine patients achieved concomitant responses in the visceral, hematologic, and biochemical parameters measured, in two patients hemoglobin levels were unchanged despite improvement in other parameters. In two additional children, visceral responses were not associated with hematologic or biochemical improvement. Bone disease did