Figure 3. The mechanisms involved in the pathophysiology of LSD.

The accumulation of undegraded substrates triggers multiple events that are currently emerging as important players in the pathogenesis of LSDs. These events include storage of secondary substrates unrelated to the defective enzyme; abnormal composition of membranes and aberrant fusion and intracellular trafficking of vesicles; impairment of autophagy; perturbation of calcium homeostasis; and mitochondrial dysfunction and oxidative stress. In addition to the events shown in the figure, in several LSDs storage triggers dysregulation of signaling pathways and activation of inflammation.