The lysosomes are required for the breakdown of intracellular molecules and compounds of all sizes. The lysosomal interior is an acidic environment and contains several different enzymes. Defects in these lysosomal enzymes result in an accumulation of the substrate in the lysosome eventually disrupting tissue function leading to enlarged and impaired organs. The affected cell systems will vary with the disorder, but all disorders involve multiple organ systems.
Suspicion of a lysosomal storage disorder can come from the physical exam (e.g. organomegaly, skeletal abnormalities, corneal clouding, or coarse features) and developmental assessment. Developmental delay with regression and/or organ dysfunction that is progressive is a hallmark of a storage disorder. Progressive cardiac, renal, hematological, or nervous system dysfunction occurring in a younger population than is typical would also prompt consideration of these disorders (e.g. renal disease, arrhythmias, valve disease, stroke, and peripheral neuropathy).
There is usually a continuum of severity and LSDs without obvious dysmorphic features or developmental delay are underrecognized. Due to the overall rarity of these conditions and their clinical heterogeneity, lengthy diagnostic delays and missed diagnoses are common.