The Sphingolipidoses are a group of Lysosomal Storage Disorders (LSDs), which individually are considered rare diseases; however, their collective incidence is approximately 1 in 5000-9000 live births. This number is dependent on the location and population, with some regions presenting a much higher proportion of cases than others. These diseases consequently together comprise a vast proportion of the healthcare system and therefore there is a need to investigate novel treatments as well as more efficient and effective diagnostic methods.
There are approximately 50 different Lysosomal storage disorders (LSDs), which involve cases where a mutation exists in a gene encoding a lysosomal enzyme required to breakdown a certain substrate. Lysosomes are important membrane bound organelles which contain many hydrolytic digestive enzymes. The lysosome is acidic and acts as the site of the breakdown of various substrates in cells. The contents is then transported and secreted via fusion with the plasma membrane of a cell. Mutations in genes encoding these enzymes cause the product to accumulate within the lysosomes of cells and have the devastating clinical manifestations associated with the disease2. The Sphingolipidoses are diseases …show more content…
This disorder is caused by a deficiency in the lysosomal enzyme, glucosyl-ceramide-ß-glucosidase, which causes the accumulation of glucosylceramide as well as the deacylated version, glucosylsphingosine (GluSph). This metabolic defect can arise through a wide range of mutational events, with approximately 150 mutations in this gene identified, which exhibit a low phenotype-genotype correlation. Therefore, Gaucher disease can present itself as phenotypic variants arising from the same mutation, as well as unknown mutations which ultimately contribute to the diverse clinical manifestations that are frequently