title: Hematological manifestations and complications of Gaucher disease.
abstract: Gaucher disease is a multisystemic metabolic disorder due to a genetic deficiency of the lysosomal enzyme glucocerebrosidase, which leads to the accumulation within the lysosomes of macrophages of its natural substrate, glucosylceramide and its deacylated product glucosylsphingosine. The most prevalent form of the disease is the so-called non-neuronopathic form (type 1) characterized by anemia, thrombocytopenia, enlargement of liver and/or spleen, skeletal abnormalities. Etiology of anemia and thrombocytopenia may be multifactorial and not necessarily predicted by the degree of splenomegaly. Bleeding diathesis may not always be related to absolute platelet count but may be influenced by abnormal platelet function or coagulation factor deficiencies. A significant increased risk of severe hematological co-morbidities, including multiple myeloma and B-cell lymphoma, has been reported. Accumulation of glucosylceramide and glucosylsphingosyne in macrophages and the resulting chronic inflammation with the secretion of cytokines leading to polyclonal and monoclonal B cell proliferation up to multiple myeloma, as a continuum clonal expansion, is a key pathophysiological mechanism. Enzyme replacement therapy has been shown to be effective in reducing glucosylceramide storage burden and the deleterious effects caused by its accumulation, including hematological manifestations.
authors.affiliation: a Department of Heart and Vessels, Center for Bleeding Disorders , Careggi University Hospital , Florence , Italy.
authors.forename: Silvia
authors.initials: S
authors.lastname: Linari
authors.affiliation: a Department of Heart and Vessels, Center for Bleeding Disorders , Careggi University Hospital , Florence , Italy.
authors.forename: Giancarlo
authors.initials: G
authors.lastname: Castaman
mesh_terms: D005776:Gaucher Disease / Q000150:complications*; D006402:Hematologic Diseases / Q000209:etiology*; D006801:Humans
keywords: activated macrophage; bleeding; enzyme replacement therapy; gaucher disease; glucosylceramide; hypergammaglobulinemia; multiple myeloma; splenomegaly; substrate reduction therapy