Gaucher disease: haematological presentations and complications

Br J Haematol. 2014 May;165(4):427-40. doi: 10.1111/bjh.12804. Epub 2014 Mar 3.

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.

Keywords: Gaucher disease; glycosphingolipid; myeloma; splenomegaly; thrombocytopenia.

Publication types

  • Review

MeSH terms

  • 1-Deoxynojirimycin / analogs & derivatives
  • 1-Deoxynojirimycin / therapeutic use
  • Anemia / etiology
  • Combined Modality Therapy
  • Disease Management
  • Enzyme Replacement Therapy
  • Gaucher Disease / blood*
  • Gaucher Disease / classification
  • Gaucher Disease / complications
  • Gaucher Disease / enzymology
  • Gaucher Disease / physiopathology
  • Gaucher Disease / therapy
  • Genetic Predisposition to Disease
  • Glucosylceramidase / genetics
  • Glucosylceramidase / physiology
  • Glycosphingolipids / metabolism
  • Hemorrhagic Disorders / etiology
  • Humans
  • Inflammation
  • Lewy Body Disease / enzymology
  • Lewy Body Disease / genetics
  • Lysosomes / metabolism
  • Lysosomes / pathology
  • Macrophage Activation
  • Multiple Myeloma / etiology
  • Parkinson Disease / enzymology
  • Parkinson Disease / genetics
  • Splenectomy
  • Splenomegaly / etiology
  • Thrombocytopenia / etiology
  • Unfolded Protein Response

Substances

  • Glycosphingolipids
  • 1-Deoxynojirimycin
  • miglustat
  • Glucosylceramidase