Conventional or novel therapy for Gaucher's disease depends upon broad clinical and basic scientific knowledge of the disorder. Many patients have been studied and important complications identified. In terms of diagnosis, methods have been developed which permit identification of cases using only a uring sample. Diagnosis of different phenotypes using a monoclonal antibody permits identification of neurologically affected cases presymptomatically. A disorder of vitamin D metabolism affecting calcium homeostasis has been described and regimens of vitamin D and calcium supplementation are being evaluated. Basic research work on glucocerebrosidase has generated a variety of new and complementary projects which address the biochemistry, cell biology, and molecular genetics of the enzyme as a part of more far-reaching studies. Glucocerebrosidase serves as a model for these studies of lysosomal enzymes and proteins. The results of this coordinated approach have revealed the structure, biosynthesis, rates of synthesis and degradation, lysosomal routing, lectin binding, and cellular uptake of the enzyme. The alteration of some of these processes have been described for the several different mutations of the gene resulting in different phenotypes of the disease. This information provides substantive new data from which the approach of enzyme replacement is perfected. A clinical trial incorporating these advances is currently underway. Other projects have resulted in the isolation, expression, and transfer of the gene for glucocerebrosidase and are leading to the consideration of gene transfer for Gaucher's disease.
