Tay-Sachs Disease

(GM2 Gangliosidosis: Hexosaminidase alpha-subunit Deficiency)

 

Epidemiology:

    • Jewish prevalence
      • Especially Ashkenazic

 

Common sites:

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Gross features:

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Histologic features:

    • accumulation of GM2 ganglioside in many tissues
      • nervous system
      • heart
      • liver
      • spleen
    • nervous system:
      • central and autonomic nervous systems and retina involved
      • neurons ballooned with cytoplasmic vacuoles
        • markedly distended lysosomes filled with gangliosides
      • over time:
        • progressive destruction of neurons
        • proliferation of microglia
        • accumulation of complex lipids in phagocytes

 

Immunophenotype:

Marker:

Sensitivity:

Specificity:

 Oil red O

 

 

Sudan black B

 

 

 

Molecular features:

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Other features:

    • EM – cytoplasmic inclusions, including whorled configurations composed of onion-skin layers of membranes
    • autosomal recessive inheritance
    • inability to catabolize GM2 gangliosides
      • mutation in alpha subunit locus on chromosome 15 for gangliosidase enzyme
    • cherry red spot in macula on retinal examination (accentuation of normal macular colour with surrounding ganglioside-swollen neurons)

 

References:

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