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Individually rare but collectively affect 1 in 5,000 live births

Lysosomal storage diseases (LSDs) are a group of over 70 diseases that are characterized by lysosomal dysfunction, most of which are inherited as autosomal recessive traits. These disorders are individually rare but collectively affect 1 in 5,000 live births. They typically present in infancy and childhood, although adult-onset forms also occur. Most LSDs have a progressive neurodegenerative clinical course, although symptoms in other organ systems are frequent. LSD-associated genes encode different lysosomal proteins, including lysosomal enzymes and lysosomal membrane protein (Platt et al, 2018). They are mainly caused by genetic mutations affecting the function of specific enzymes, transporters, receptors or hormones involved in metabolizing and transporting the body’s building blocks such as sugars, proteins and lipids. These malfunctions can impair either the assembly of crucial metabolic end-products which are needed for the normal function of the body or lead to harmful accumulations of intermediate metabolites. GM1 gangliosidosis and GM2 gangliosidosis (Tay-Sachs and Sandhoff diseases), Niemann-Pick type A/B, Krabbe, Farber, Fabry and Gaucher diseases are examples of lysosomal sphingolipid storage disorders.

Lysosomal Storage disorders and their impact on patients

Depending on the affected pathway, storage disorders can lead to harmful metabolite accumulations in different organs and body parts including, not exclusively, the liver, spleen, heart, kidney, skin, bones, and brain.

Symptoms therefore range anywhere from organ enlargement/dysfunction, abnormal bone growth, impaired hearing and vision, developmental delay, and cognitive dysfunction to neuropathological effects such as seizures and movement disorders. As these diseases are triggered by the relevant inherited mutations, multiple primary defects can be detected early on, sometimes leading to the premature death of newborns and young children. In some of these rare metabolic diseases, patients may reach adult age while affected by severe progressive morbidity

Regardless of the defective pathway, early treatment is critical for these genetic diseases given their progressive nature and severity. Although specific therapies are now available for some of these diseases, many patients can only receive palliative care with marginal or no improvements when it comes to these neuronopathic conditions.