ABSTRACT
Many of these disorders are due to deficiencies of a particular lysosomal enzyme, which plays an essential role in the degradation of various normal metabolites or the breakdown products of cells. As a result, the undegraded material accumulates in, and causes enlargement of, the lysosomes of certain cells. The distribution of structural abnormalities depends on the particular enzyme deficiency, some of the disorders affecting the CNS, others the peripheral nervous system or muscle, and others both the nervous system and visceral organs such as liver, spleen and lymph nodes. Affected cells become enlarged and have a ballooned appearance (Fig. 12.1), hence the previous term of neuronal storage disorders. Stored material can be detected histochemically: frozen sections are essential because lipids dissolve in alcohol and mucopolysaccharides in water. Stains required include oil red O and Sudan black B for lipids; Luxol fast blue, which is traditionally regarded as a stain for complex lipids; PAS with and without diastase for glycogen and other carbohydrate-containing constituents; toluidine blue, or acidified cresyl violet for metachromatic leukodystrophy; and toluidine blue for mucopolysaccharides. A range of histochemical techniques, both non-specific and highly specific,
is now available for the identification of the stored material. It is often necessary, however, to correlate the histochemical findings with the clinical and morphological features so as to identify a clinicopathological pattern of a particular disease. In many instances, the precise diagnosis can be made on a block of unfixed tissue frozen for biochemical analysis, including thin-layer and gas-liquid chromatography and enzyme assays. Electron microscopy is also essential since this will demonstrate grossly enlarged lysosomes containing non-metabolizable residue. At one stage it was considered that the distinctive ultrastructural features of some disorders were such that morphology could be used to
Figure 12.1 Mucopolysaccharidosis. The neurons are greatly distended by stored material. PAS.
