The lysosomal storage disorders result from various enzymatic defects, which include the absence of an enzyme activator or a protective protein, lack of a substrate activator
protein, lack of a transport protein required for egress from the lysosome, defects in posttranslational processing, or synthesis of catalytically inactive proteins (552). The sites that are affected are those where the specific substrates need to be metabolized. Lysosomal storage diseases are usually classified into three categories: (a) sphingolipidoses (Gaucher disease); (b) mucopolysaccharidoses (Hurler and Hunter diseases); and (c) glycogen storage disease (Pompe disease) (Table 13.28). All three categories show variable severity and time of onset. The lysosomal disorders are usually diagnosed by enzymatic assay of white blood cells or fibroblasts or by rectal biopsies. Acid phosphatase stains highlight the intracellular inclusions present in lysosomal storage diseases. The tissues may also be examined by PAS, Luxol fast blue, and Sudan black stains, and for acid phosphatase activity, as well as examined under ultraviolet light to show accumulations of autofluorescent material (553). Most individuals advocate use of both histologic and ultrastructural examination to document the disease (553). Because the stored substances are often lipids, frozen sections are necessary to demonstrate the abnormal accumulations. Thus, when such a disease is suspected, a piece of unfixed tissue must be snap-frozen for further analysis.