Pathogenic mechanisms at the basis of LSDs

The pathophysiology and pathogenesis of lysosomal diseases is understood in broad terms, but the fine details of the processes are lacking for the majority of these diseases.

Each lysosomal storage disorder and each patient with a given lysosomal disorder has unique genetic, molecular, pathologic and clinical features, but the order of pathogenic events is largely the same. Mutations in genes encoding a lysosomal function cause lysosomal dysfunction, which in turn results in cellular pathology affecting organ structure and function. Secondary effects also occur and recent data suggest that mechanisms including systemic inflammation, autophagy and apoptosis may be involved.
It is not clear whether these mechanisms are common to different lysosomal diseases or are due to the storage of specific substrates.
An improved understanding of the role of these mechanisms in the pathogenesis of LSDs will raise the question as to whether therapies aimed at the treatment of secondary effects will be of help in stopping or delaying disease progression, alone or in combination with other therapies such as enzyme replacement, enzyme enhancement, substrate reduction and gene therapy.