Epidemiology and natural history of Gaucher's disease

Gaucher's disease was first described by Philippe Gaucher in 1882, who recognized that this was a systemic disease. The biochemical defect, genetic basis and molecular epidemiology have subsequently been characterized. Gaucher's disease arises as a result of a deficiency of glucocerebrosidase and is the commonest of the lysosomal storage disorders. The overall incidence is approximately 1:40,000 individuals, but it is much commoner amongst individuals of Ashkenazi Jewish origin. A small number of genotypes are characteristically encountered amongst this population and the commonest of these (N370S) encodes an enzyme that has sufficient residual enzyme activity to ensure that significant neurologic disease does not occur. The main clinical features of adult Gaucher's disease are organ enlargement (liver and spleen), bone marrow infiltration leading to anaemia, thrombocytopenia and leucopenia, and skeletal involvement leading to bone pain and pathological fracture. There is also an association with Parkinson's disease, cancer and lymphoproliferative disease, illustrating that Gaucher's disease is a multi-system disorder with manifestations in most organ systems. The underlying pathophysiology is imperfectly understood, but it is increasingly clear that inflammation mediated by cytokines is responsible for a significant part of the pathology.