Tay-Sachs and Niemann-Pick
Tay–Sachs disease and Niemann–Pick disease are autosomal recessive lysosomal storage disorders characterized by a cherry-red macula on exam. They are both sphingolipidoses, each of which is caused by a build-up of sphingolipids in body tissues. First, Tay–Sachs disease is caused by a deficiency of β-hexosaminidase A, which leads to a buildup of GM2 ganglioside within cells. This leads to cellular toxicity and is responsible for the signs and symptoms of Tay–Sachs disease. Notably, the accumulation of GM2 ganglioside leads to the destruction of nerve cells. Signs and symtoms include neurodegeneration, developmental delay, and the appearance of onion-skin lysosomes on EM biopsy. Similarly, Niemann–Pick disease is caused by the accumulation of sphingomyelin within cells. Different signs and symptoms occur depending on where the sphingomyelin accumulates. In contrast to Tay–Sachs disease, sphingomyelin builds-up in the liver and spleen and leads to hepatosplenomegaly. The disease is also characterized by the presence of foam cells, which are lipid-laden cells seen on biopsy.