Lipoprotein metabolism in type l gaucher disease patients on enzyme therapy

Type l Gaucher disease (GD), an inherited disorder of glucosylceramide metabolism, is due to deficiency of lysosomal acid B-gtucosidase. Untreated GD patients show reduced concentrations of plasma total, low density (LDL), and high density (HDL) cholesterol which are inversely correlated to clinical disease severity, hi addition, plasma levels of apolipoprotein B (apoB) and apoA-I are reduced. These changes are attributed to an increased catabolism of both LDL and HDL as result of macrophage activation (Le et. al.. Metabolism 37:240-245,1988) Recent studies of GD patients given regular intravenous infusion of placental-derived or recombinant human glucocerebrosidase revealed hematopoietic reconstitution and reversal of organomegaly. To determine the impact of enzyme therapy on lipoprotein abnormalities, serial determinations of plasma total, LDL, and HDL cholesterol, triglycéride, and apo A-I and B levels were performed on 32 GD patients. There were equal numbers of males and females; mean age 38.0±_ 19.3 yean old (nmge6-80), with 7 patients < 18 yr. All but 1 patient had hepatomegaly and 14 patients had undergone previous splenectomy. Anemia (S s= 10.6 ±1.5 gm%) and thrombocytopenia (£=86.4 ±3IK) were noted in 88% and 53% of the patients. There were no sex-related differences in disease severity, as measured by degree of liver or spleen enlargement. On therapy (x̄=26 ±12 months), significant increases were observed in plasma total and HDL chol levels. A trend towards increasing LDL chol and A-I levels also was noted. The lipid changes were associated with significant increases in blood counts (△Hg x̄ 1.7 gm%;A platelets x̄ = 20,000/mm1 ) and reduction of organomegaly (△ liver volume x̄ - 31.4%; & spleen volume x̄ 50%). The changes in lipid profile towards the normal levels as a result of enzyme replacement most likely reflect metabolic homeostasis achieved with reduction of the systemic burden of disease and/or reduction in the number of activated macrophages.