Medicine & USMLE

Tay-Sachs and Niemann-Pick

Lysosomal Storage Diseases
  1. Krabbe Disease
  2. Hurler and Hunter Syndromes
  3. Fabry Disease
  4. Tay-Sachs and Niemann-Pick
  5. Gaucher Disease
  6. Metachromatic Leukodystrophy
  7. I-Cell Disease


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.

Tay–Sachs Disease is caused by a deficiency of β-hexosaminidase A, which leads to a buildup of GM2 ganglioside within cells. Notably, the accumulation of GM2 ganglioside leads to the destruction of nerve cells. Signs and symptoms include neurodegeneration, developmental delay, and the appearance of onion-skin lysosomes on EM biopsy.

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.

Key Points

  • Both Diseases
    • Cherry red spot on macula
    • Neurodegeneration
      • CNS damage
      • Regression of developmental milestones
      • Seizures, hypotonia, and changes to reflexes (hyperreflexia or areflexia) may be seen
    • Autosomal recessive inheritance
  • Unique to Niemann-Pick Disease
    • Deficient sphingomyelinase
      • Impaired sphingolipid degradation causes accumulation of sphingomyelin
      • Foam cells on neural biopsy
        • Accumulation of sphingolipids leads to lipid-laden macrophages
    • Associated with Ashkenazi Jewish descent
    • Hepatosplenomegaly
      • Due to accumulation of sphingomyelin-laden histiocytes in liver and spleen
  • Unique to Tay-Sachs Disease
    • Deficient hexosaminidase A
      • Accumulation of GM2 ganglioside
    • Neural biopsy reveals onion skin lysosomes
      • Accumulation of gangliosides causes distension of lysosomes

Find Tay-Sachs Disease, Niemann-Pick Disease, and more Lysosomal Storage Diseases among Pixorize's visual mnemonics for the USMLE Step 1 and NBME Shelf Exams.