title: Gaucher disease: haematological presentations and complications.
abstract: Gaucher disease (GD) is an autosomal recessive lysosomal storage disease, caused by deficiency of the enzyme glucocerebrosidase, required for the degradation of glycosphingolipids. Clinical manifestations include hepatosplenomegaly, thrombocytopenia, bone disease and a bleeding diathesis, frequently resulting in presentation to haematologists. Historically managed by splenectomy, transfusions and orthopaedic surgery, the development of specific therapy in the form of intravenous enzyme replacement therapy in the 1990s has resulted in dramatic improvements in haematological and visceral disease. Recognition of complications, including multiple myeloma and Parkinson disease, has challenged the traditional macrophage-centric view of the pathophysiology of this disorder. The pathways by which enzyme deficiency results in the clinical manifestations of this disorder are poorly understood; altered inflammatory cytokine profiles, bioactive sphingolipid derivatives and alterations in the bone marrow microenvironment have been implicated. Further elucidating these pathways will serve to advance our understanding not only of GD, but of associated disorders.
authors.affiliation: Lysosomal Storage Disorders Unit, Royal Free Hospital, London, UK.
authors.forename: Alison S
authors.initials: AS
authors.lastname: Thomas
authors.forename: Atul
authors.initials: A
authors.lastname: Mehta
authors.forename: Derralynn A
authors.initials: DA
authors.lastname: Hughes
mesh_terms: D017485:1-Deoxynojirimycin / Q000031:analogs & derivatives / Q000627:therapeutic use; D000740:Anemia / Q000209:etiology; D003131:Combined Modality Therapy; D019468:Disease Management; D056947:Enzyme Replacement Therapy; D005776:Gaucher Disease / Q000097:blood* / Q000145:classification / Q000150:complications / Q000201:enzymology / Q000503:physiopathology / Q000628:therapy; D020022:Genetic Predisposition to Disease; D005962:Glucosylceramidase / Q000235:genetics / Q000502:physiology; D006028:Glycosphingolipids / Q000378:metabolism; D006474:Hemorrhagic Disorders / Q000209:etiology; D006801:Humans; D007249:Inflammation; D020961:Lewy Body Disease / Q000201:enzymology / Q000235:genetics; D008247:Lysosomes / Q000378:metabolism / Q000473:pathology; D008262:Macrophage Activation; D009101:Multiple Myeloma / Q000209:etiology; D010300:Parkinson Disease / Q000201:enzymology / Q000235:genetics; D013156:Splenectomy; D013163:Splenomegaly / Q000209:etiology; D013921:Thrombocytopenia / Q000209:etiology; D056811:Unfolded Protein Response
chemical_list: D006028:Glycosphingolipids; D017485:1-Deoxynojirimycin; C059896:miglustat; D005962:Glucosylceramidase
keywords: Gaucher disease; glycosphingolipid; myeloma; splenomegaly; thrombocytopenia