Children with Tay-Sachs disease carry mutations that eliminate hexosaminidase A activity. Inside their neurons, which direct consequence follows from this lysosomal defect?

Core Concept

Hexosaminidase A normally clips the final sugar from GM2 ganglioside inside lysosomes. Without it, membrane lipid arriving through normal turnover accumulates in expanding lysosomes, distending neurons and disrupting signaling. Because the defect lies in degradation, synthesis continues and the undegraded stockpile grows throughout development.