TY - JOUR
T1 - Southwestern Internal Medicine Conference
T2 - Gaucher disease: A heterogeneous clinical complex for which effective enzyme replacement has come of age
AU - Frenkel, E. P.
N1 - Funding Information:
From the Harold C. Simmons Comprehensive Cancer Center and Department of Internal Medicine, Division of Hematology, University of Texas Southwestern Medical Center at Dallas, Texas. Supported in part by the Nasher Family Cancer Research Fund; Dallas, Texas. Correspondence: Eugene P. Frenkel, MD, Department of Internal Medicine, Division of Hematology, University of Texas Southwestern Medical Center at Dallas, Dallas, TX 75235-8852.
PY - 1993
Y1 - 1993
N2 - Gaucher disease, the most common form of lysosomal storage disease, is the result of autosomal recessive inheritance of a lysosomal enzyme glucocerebrosidase deficiency, which produces defective hydrolysis of glucosylceramide that accumulates in reticuloendothelial (tissue macrophage) cells. The current review focuses on Type 1 (the nonneuronopathic) or adult Gaucher disease and defines the clinical manifestations (splenomegaly, hepatomegaly, bony lesions, and clinical metabolic dysfunction) in relationship to the known enzymatic defect. The clinical diversity and variability in symptoms and signs, the age at onset of the clinical manifestations and their rate of progression, and the heterogeneity of the organs involved are reviewed. Extensive delineation of the nature of the enzyme defect and the recent molecular characterization of the enzyme mutants has not provided an explanation for the remarkable clinical phenotypic heterogeneity. Enzyme assays now provide an excellent method for diagnosis. Effective enzyme replacement therapy emphasizes the value of early diagnosis and has altered the costs and potential risks of older therapeutic indications for splenectomy or cytokine therapy. Enzyme efficacy raises questions about the specific indications for replacement treatment and the most desirable rate and duration of enzyme delivery.
AB - Gaucher disease, the most common form of lysosomal storage disease, is the result of autosomal recessive inheritance of a lysosomal enzyme glucocerebrosidase deficiency, which produces defective hydrolysis of glucosylceramide that accumulates in reticuloendothelial (tissue macrophage) cells. The current review focuses on Type 1 (the nonneuronopathic) or adult Gaucher disease and defines the clinical manifestations (splenomegaly, hepatomegaly, bony lesions, and clinical metabolic dysfunction) in relationship to the known enzymatic defect. The clinical diversity and variability in symptoms and signs, the age at onset of the clinical manifestations and their rate of progression, and the heterogeneity of the organs involved are reviewed. Extensive delineation of the nature of the enzyme defect and the recent molecular characterization of the enzyme mutants has not provided an explanation for the remarkable clinical phenotypic heterogeneity. Enzyme assays now provide an excellent method for diagnosis. Effective enzyme replacement therapy emphasizes the value of early diagnosis and has altered the costs and potential risks of older therapeutic indications for splenectomy or cytokine therapy. Enzyme efficacy raises questions about the specific indications for replacement treatment and the most desirable rate and duration of enzyme delivery.
KW - Gaucher Disease
KW - Glucocerebrosidase
KW - Glucosylceramide
KW - Lysosomal storage defect
KW - Nonneuronopathic Gaucher
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U2 - 10.1097/00000441-199305000-00014
DO - 10.1097/00000441-199305000-00014
M3 - Article
C2 - 8097903
AN - SCOPUS:0027298204
SN - 0002-9629
VL - 305
SP - 331
EP - 344
JO - American Journal of the Medical Sciences
JF - American Journal of the Medical Sciences
IS - 5
ER -