Neuronopathic forms of Gaucher's disease.

Neuronopathic Gaucher patients may have a wide variety of clinical manifestations and natural history, and can present with a range of degrees of severity of systemic disease and neurological deficit. The brain pathology of these patients has been well described, but the mechanism by which glucocerebrosidase deficiency leads to neuronal dysfunction is not yet understood. The almost 20 different mutations of the glucocerebrosidase gene that have been described in Type 2 and 3 Gaucher patients poorly predict the phenotype of individual patients. Enzyme replacement therapy (ERT), often at high doses, has been shown to reverse most of the systemic manifestations of this disease, but can rarely reverse the neurological deficits. Therefore, other forms of treatment, such as gene therapy or a more efficient and direct enzyme delivery to neurons, are being devised.