The gangliosidoses comprise a family of lysosomal storage diseases characterized 
by the accumulation of complex glycosphingolipids in the nervous system and 
other tissues, secondary to the deficient activity of lysosomal hydrolases or 
their associated activator proteins. GM1 and GM2 gangliosidosis are associated 
with deficiency of β-galactosidase and β-hexosaminidase respectively. All 
gangliosidoses are characterized by progressive neurodegeneration, the severity 
of which is proportional to the residual enzyme activity. The GM1 gangliosidoses 
are characterized by dysostosis, organomegaly and coarsening in their most 
severe forms, whereas children with classic infantile GM2 gangliosidosis 
(Tay-Sachs disease) are usually spared systemic involvement, except in the case 
of the Sandhoff variant, in which organomegaly may occur. Cherry-red macular 
spots occur in the early onset forms of the gangliosidoses, but are less 
frequently seen in the less severe, later onset phenotypes. Macrocephaly, an 
exaggerated startle response, cognitive decline, seizures, ataxia, and 
progressive muscular atrophy may occur in different forms of gangliosidosis. The 
diagnosis is made by assay of enzyme activity, and can be confirmed by mutation 
analysis. Carrier screening for Tay-Sachs disease has been remarkably successful 
in reducing the incidence of this disease in the at-risk Ashkenazi population. 
There are no proven disease-modifying therapies for the gangliosidoses.