NEURONOPATHIC FORMS OF GAUCHERS-DISEASE

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