Pathogenesis of neurologic disease associated with lysosomal storage diseases

(A) Single gene is mutated
(B) Insufficient enzyme activity
(C) Storage of primary substrate

1. neuronal swelling
2. secondary or primary glycolipid substrate accumulation
   --> GM2 ganglioside storage in neurons -->

• neurite sprouting --> abnormal synapses
• meganeurites

(D) both 1 & 2 above lead to neural dysfunction