Lysosomals

Lysosomal storage diseases (LSDs) are a group of inherited metabolic disorders that result from lysosomal dysfunction. Most LSDs are autosomal recessively inherited disorders, with only three exceptions that are X-linked. The overall incidence is about 1 in 5000 live births. Mutations in genes encoding lysosomal proteins cause lysosomal malfunction with the gradual accumulation of substrates leading to cell dysfunction and cell death. LSDs are generally classified based on the biochemical type of accumulated substrate that leads to a heterogeneous spectrum of clinical manifestations. The diagnostic suspicion of LSDs is based on clinical symptoms, and the measurement of the abnormal accumulation of substrates in biological fluids. The diagnosis is confirmed by enzymatic and/or genetic analysis, including next-generation sequencing and whole exome sequencing. In the last years, many efficient therapies have been developed. New treatments and the evidence that the early treatment shortly after birth can permit a better outcome have led to the development of several pilot newborn screening programs for some LSDs. Early detection in a presymptomatic state and prompt treatment can modify the natural history of LSD disease preventing irreversible damage of the involved key organs.