This is what happens in general when you have an accumulation of a substrate due to a deficiency in an enzyme in the lysosome. The substrate accumulates initially within the lysosome and then with spillage, and with increase in those substrate accumulations you can have enlarged organs,  bone disease, bone marrow infiltration, kidney disease, brain and nervous system involvement, heath involvement, change in your facial features, skin changes - these are called angiokeratomas, they are deposition in the capillaries of the skin which then pop out of the skin and they give this reddish discolouration, mongolian spots and muscle and joint problems.

The key to the pathophysiology of lysosomal storage disease is that the severity of each of these diseases really depends on the residual enzyme activity. We all are supposed to have 100% enzyme activity for every enzyme we have. 50% can be carried by each copy of the gene that we have. If we are carriers of lysosomal storage disease and we have one copy of our gene that is defective we can still survive properly without having symptoms because we have that second copy that can do 50% of the work. In general people start developing symptoms of lysosomal storage disease when that level of activity drops below 5%, so we can do well even with more than 5 to 10% of our enzyme activity. Depending on how much residual activity you have when you an LSD you can have a milder phenotype, milder symptoms, vs very severe symptoms, vs lethal symptoms that can cause death very early after birth. Most patients that have lysosomal storage disease are normal at birth, because the material starts accumulating in utero, and as you get older you have more substrate accumulation in your tissues and the more the substrate accumulates the more dysfunction you have in your tissue, and then at some point you reach a threshold where your body cannot handle that accumulation anymore, and the disease expresses itself. That can happen anywhere from infancy into late adulthood.


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