ABSTRACT
Tay-Sachs disease has been described as the prototype of the lysosomal storage disorders. It represents a paradigm for the success of research in biochemical genetics not only in providing precise molecular understanding of the nature of disease but also in the practical community-based control of a genetic disease. Patients with Tay-Sachs disease appear normal at birth, although storage of GM2 ganglioside has been demonstrated even in the fetus. An assay has been developed in which fibroblasts of the various phenotypes have had activities of hexosaminidase A that correlated well with the clinical picture. Tay-Sachs disease is transmitted as an autosomal recessive disease. Heterozygous carriers of the gene have intermediate activities of hexosaminidase A in their serum or plasma. Pyrimethamine has been found to increase hexosaminidase activity, slowing the progression of late onset Tay-Sachs disease. Sialidase has been used in vivo to deplete cultured Tay-Sachs cells of GM2 ganglioside.
