Sandhoff disease may be clinically indistinguishable from Tay-Sachs disease even though the same enzyme is defective (albeit in separate subunits A and B that together comprise the functional enzymes). The presence of hepatosplenomegaly in Sandoff disease may be distinguishing. The infantile form of this lysosomal storage disease seems to be the most severe. Infants appear to be normal until about 3-6 months of age when neurological development slows and muscles become weak. Seizures, loss of interest, and progressive paralysis begin after this together with loss of vision and hearing. An exaggerated startle response is considered an early and helpful sign in the diagnosis. Among infants with early onset disease, death usually occurs by 3 or 4 years of age.
Ataxia with spinocerebellar degeneration, motor neuron disease, dementia, and progressive dystonia are more common in individuals with later onset of neurodegeneration. The juvenile and adult-onset forms of the disease also progress more slowly.
