Enzyme augmentation in moderate to life-threatening gaucher disease

• Published in: Pediatric research Vol. 31; no. 5; pp. 496 - 502
• Main Authors: FALLET, S, GRACE, M. E, SIBILLE, A, MENDELSON, D. S, SHAPIRO, R. S, HERMANN, G, GRABOWSKI, G. A
• Format: Journal Article
• Language: English
• Published: Hagerstown, MD Lippincott Williams & Wilkins 01.05.1992
• Subjects: acid beta -glucosidase; Adolescent; Adult; Anemia - drug therapy; Biological and medical sciences; Child; Child, Preschool; enzyme augmentation; Errors of metabolism; Female; Gaucher Disease - blood; Gaucher Disease - drug therapy; Gaucher Disease - enzymology; Gaucher's disease; Glucosylceramidase - administration & dosage; Glucosylceramidase - deficiency; Glucosylceramidase - pharmacokinetics; Glucosylceramidase - therapeutic use; Hepatomegaly - drug therapy; Humans; Lipids (lysosomal enzyme disorders, storage diseases); Male; Medical sciences; Metabolic diseases; Middle Aged; Splenomegaly - drug therapy; Thrombocytopenia - drug therapy; Tissue Distribution; treatment; Human; Nervous system diseases; Replacement therapy; Gaucher disease; β-D-Glucosidase; Enzyme; Metabolic diseases; Lipids; Enzymopathy; Child; Genetic disease
• ISSN: 0031-3998; 1530-0447
• DOI: 10.1203/00006450-199205000-00018

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.