Introduction

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 over 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 32.1.

These diseases are classified by the nature of the stored material that results from the defects in selected lysosomal enzymes, their cofactors, and/or enzyme or substrate transport (Table 32.1). The lysosomal storage diseases are heterogeneous, progressive, multisystem diseases that have a spectrum of ages of onset, severity, rate 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 rare, the combined birth prevalence is approximately 1 in 7 000 live births [2]. The diseases are traditionally diagnosed biochemically, but in many cases may also be confirmed molecularly by the identification of pathogenic mutations in one or both copies (X-linked conditions or autosomal recessive, respectively) of the specific genes.