Diagnostic approach to spontaneous neuropathic lysosomal storage diseases of dogs and cats.

Lysosomes are subcellular membrane-bound organelles containing acidic hydrolases and are involved in the degradation of cellular components. Lysosomal storage diseases (LSDs) are a heterogeneous group of inherited metabolic disorders associated with lack or inadequacy of functional enzymes of the metabolism of complex lipids and complex carbohydrates (i.e. glycolipids, glycoproteins, and glycosaminoglycans). The inactivity of one or more enzymes induces a catabolic blockade of the substrate and subsequent accumulation of incompletely degraded macromolecules within lysosomes4. Although most LSDs result from acidic hydrolase deficiencies, some of these conditions result from defects in lysosomal membrane proteins or non-enzymatic soluble lysosomal proteins11. The clinicopathological profile of each disease is determined by the cell types where storage occurs and the degree of protein function affected by specific mutation. In all cases, the accumulation of the endolysosomal substrate progressively prevents the normal cell function, and then invariably determines cell death through several mechanisms (i.e. apoptosis, synaptic modifications, toxic effect of the storage substrate). The aim of this presentation is to report on the available information on these rare diseases in dogs and cats and to propose a diagnostic approach based on the clinical and pathological features which characterize the different diseases.