Clinical, biochemical and genetic heterogeneity in lysosomal storage diseases

textabstractThe history of lysosomal storage diseases dates back to the end of the last century when the first clinical reports appeared of patients suffering from these genetic, metabolic disorders (Tay, 1881; Gaucher, 1882; Sachs, 1887; Fabry, 1898). About seventy years wouid pass before the term 11 "lysosome" was introduced by De Duve and co-workers (1955, 1965) to indicate a membrane-surrounded cytoplasmic particle containing acid hydrolases that was isolated by centrifugal cell fractionation. Later, the lysosomes were cytochemically demonstrated by Novikoff (1961) using an appropriate staining reaction for acid phosphatase and some other acid hydrolases. In the period that followed an impressive amount of work has been carried out on the structure and function of lysosomes (see for review Dingle and Fell, 1969-1975) and at present a few dozen of different acid hydrolases is known to be localized within this organe-lle. The main function of the lysosomal enzymes is the degradation of material that is enclosed in secondary lysosomes by fusion of the primary lysosome with hetero- and autophagosomes or by other processes