Lysosomal beta-hexosaminidase occurs as two major isozymes hexosaminidase A and B. The alpha subunit is encoded by the HEXA gene and the subunit by HEXB gene. Defects in the beta subunit lead to Sandhoff disease. Patients with the defect lack the activity or formation of both hexosaminidase A and B. The disorders are classified according to the age of onset, as infantile, juvenile and adult form. Recent molecular genetic analysis has revealed a 50 kb deletion, 16 kb Alu type deletion, and compound heterozygous with other mutations. In the juvenile or adult type of the disease, point mutation of the HEXB gene, creating a new 3' splice acceptor site. The correlation of the clinical phenotype and the gene abnormalities is discussed.