Substantial evidence supports a disease model for TSD and SD which attributes pathology to decreased or absent Hex A levels in neuronal lysosomes of the brain. The problem in GM2 - gangliosidosis is the inability of the cell to metabolize GM2 gangliosides. When the residual activity of Hex A falls below a critical threshold level, GM2 ganglioside influx into the lysosome (the site of Hex A activity) exceeds the degradation rate and excess substrate continuously accumulates. Consequently, the lysosomes increase in size and number, giving rise to a storage disease.