Twenty years of treatment for Gaucher disease: emerging challenges

Gaucher disease is an autosomal recessively inherited lysosomal storage disorder (LSD). Type I Gaucher disease, the so-called non-neuronopathic variant, is mainly characterised by cytopenia, hepatosplenomegaly and bone complications. Gaucher disease was the first LSD for which enzyme replacement therapy (ERT) became available in the early 90s. Studies have shown ERT to be highly effective in reversing cytopenia, reducing organomegaly and decreasing bone marrow infiltration. In this thesis the pathophysiology of long-term complications of Gaucher disease ,and the effect of ERT on these, is studied with special attention for the cost-effectiveness of ERT. Furthermore, a number of important markers to study disease severity is evaluated.
The thesis shows that ERT can reduce the incidence of long-term complications, i.e. the need for splenectomy and the incidence of bone complications. Nonetheless, costs of treatment per quality adjusted life-year (QALY) are high.
Bone complications have an important impact on the quality of life of patients and are hypothesized to result from an imbalance in bone remodelling, characterized by a decrease in bone formation. Finally, it is increasingly recognized that malignancies represent one of the long-term complications of Gaucher disease. This is particularly true for the haematological malignancies, but includes the hepatocellular carcinoma as well.