Lysosomes are membrane-bound cellular organelles that contain multiple hydrolases needed for the digestion of various macromolecules, including mucopolysaccharides, glycosphingolipids, and oligosaccharides . The lysosomal storage diseases are a group of more than 40 diseases that are characterized by defective lysosomal function leading to an accumulation of specific substrates within the lysosomes and eventual impairment of cellular function. A schematic of the lysosomal system, enzyme trafficking, and substrate accumulation is shown in Figure 30.1.
These diseases are classified by the nature of the stored material that results from defects in selected lysosomal enzymes, their cofactors, and/or enzyme or substrate transport (Table 30.1). The lysosomal storage diseases are heterogeneous, progressive, multisystemic diseases that have a spectrum of ages of onset, severity, rates of progression, and organ involvement. Lysosomal storage diseases have significant morbidity and mortality in the absence of effective treatment. The majority of these diseases are autosomal recessive, and although individually each is rare, the combined birth prevalence is approximately 1 in 7000 live births . The diseases are traditionally diagnosed biochemically but in many cases, may also be diagnosed molecularly by the discovery of pathogenic mutations in both copies of the particular gene.
The liver is nearly always involved in lysosomal storage diseases; this can be seen at the light or electron microscopic level. The degree of clinical involvement depends on the disorder. In many cases, mild elevations in liver studies and hepatomegaly are the only manifestations. However, significant hepatic injury may be present, resulting in considerable morbidity.