title: Enzyme augmentation in moderate to life-threatening Gaucher disease.
abstract: Gaucher disease type 1 (GD type 1) is the most prevalent lysosomal storage disease and has its highest frequency in the Ashkenazi Jewish population. Deficiency of the enzyme, acid beta-glucosidase, results in the deposition of glucocerebroside primarily in macrophages. The accumulation of such "Gaucher cells" leads to visceromegaly, hepatic and bone marrow dysfunction, hypersplenism, and bony disease. Eleven GD type 1 patients, ages 4-52 y, with moderate to life-threatening manifestations, received 6-12 mo of enzyme augmentation with a macrophage-targeted acid beta-glucosidase preparation. Within 6 mo, substantial increases in Hb levels (mean = +30%) and platelet counts (mean = +39%) were observed. Hepatic and splenic volumes decreased by approximately 20% (range = 3-35%) and approximately 35% (20-52%), respectively. Hematologic and hepatic volume improvements were similar in the splenectomized (n = 4) and nonsplenectomized (n = 7) patient groups. In this patient population, no major differences were observed in the hematologic and visceral improvements with enzyme doses of 30, 50, or 60 IU/kg administered every 2 wk. Normal levels of acid beta-glucosidase activity were present in hepatic autopsy samples from one patient 11 d after enzyme infusion. In comparison, exogenous activity was absent from brain and lung specimens of the same patient. High levels (approximately 10-fold normal) were present in bone marrow samples from two patients obtained at 1 and 11 d after infusions. These studies demonstrate biochemical and clinical improvements by targeted enzyme augmentation in GD type 1, even in far advanced, life-threatening involvement.(ABSTRACT TRUNCATED AT 250 WORDS)
authors.affiliation: Department of Pediatrics, Mount Sinai School of Medicine, New York, New York 10029-6574.
authors.forename: S
authors.initials: S
authors.lastname: Fallet
authors.forename: M E
authors.initials: ME
authors.lastname: Grace
authors.forename: A
authors.initials: A
authors.lastname: Sibille
authors.forename: D S
authors.initials: DS
authors.lastname: Mendelson
authors.forename: R S
authors.initials: RS
authors.lastname: Shapiro
authors.forename: G
authors.initials: G
authors.lastname: Hermann
authors.forename: G A
authors.initials: GA
authors.lastname: Grabowski
mesh_terms: D000293:Adolescent; D000328:Adult; D000740:Anemia / Q000188:drug therapy; D002648:Child; D002675:Child, Preschool; D005260:Female; D005776:Gaucher Disease / Q000097:blood / Q000188:drug therapy* / Q000201:enzymology; D005962:Glucosylceramidase / Q000008:administration & dosage / Q000172:deficiency / Q000493:pharmacokinetics / Q000627:therapeutic use*; D006529:Hepatomegaly / Q000188:drug therapy; D006801:Humans; D008297:Male; D008875:Middle Aged; D013163:Splenomegaly / Q000188:drug therapy; D013921:Thrombocytopenia / Q000188:drug therapy; D014018:Tissue Distribution
chemical_list: C070292:alglucerase; D005962:Glucosylceramidase