Lysosomal Storage Diseases, Focusing On Gaucher Disease: Perspectives And Principles

Lysosomal storage diseases (LSDs) comprise of 60 or so monogenic disorders with a combined frequency of approximately 1:7000 live births. Deficiencies result in cellular and organ damage due to subsequent accumulation (“storage”) of a specific substrate for that particular enzyme; however, the central role of the lysosome in cellular metabolism leads to widespread pathological consequences. Hematologic manifestations include anemia, splenomegaly, thrombocytopenia, morphologic changes in peripheral blood and bone marrow, gammopathy, bone lesions, hyperferritinemia, bleeding, thrombosis, and disturbances in coagulation and platelet function. Hematologists across the spectrum of the specialty (pediatric, malignant, transplantation, coagulation and hemostasis, transfusion medicine, laboratory medicine) are likely to encounter these conditions. Diagnosis is straightforward once it is suspected; but delay in diagnosis is common and leads to inappropriate investigations, delay in specific treatment, and avoidable complications. Management should be coordinated in a multidisciplinary specialist center with regular monitoring. Specific treatment with enzyme replacement, substrate reduction, and chaperone therapy is increasingly available. Cellular and gene therapy approaches are in trial.