Low-Dose High-Frequency Enzyme Replacement Therapy Prevents Fractures without Complete Suppression of Painful Bone Crises in Patients with Severe Juvenile Onset Type I Gaucher Disease,

ABSTRACT: Patients with type I Gaucher disease often present as adults with a mild disease and with less severe genetic mutations, especially 1226G/1226G (N370S/N370S). Patients presenting as children have an excess of compound heterozygotes of N370S and other mutations, such as 84GG, 1448C (L444P) and IVS2+1 in whom bone disease is common. We report our experience with low-dose high-frequency enzyme replacement therapy in such severely affected children. Ten patients (with severe juvenile onset type I Gaucher disease) were treated. Alglucerase (Ceredase) was infused at 30 units/kg/month in 13 fractions/month for more than one year. Bone disease was used as the main criterion for evaluating treatment results. No fractures occurred in spite of the fact that bone crises occurred in four patients after 12 to 24 months of treatment, in two during the third year, and in one during the fifth year. Nonosseous manifestations improved with treatment. The ability of low-dose high frequency alglucerase to prevent fractures in the presence of continuing bone crises was demonstrated