Lysosomal storage disease

Standard classification The lysosomal storage diseases are generally classified by the nature of the primary stored material involved, and can be broadly broken into the following: (ICD-10 codes are provided where available) • (E75) Lipid storage disorders • Gangliosidoses (including Tay–Sachs disease (E75.0-E75.1) - they are a subtype of sphingolipidoses • Sphingolipidoses that are not gangliosidoses, including Gaucher's and Niemann–Pick diseases (E75.2-E75.3) • Leukodystrophies • (E76.0) Mucopolysaccharidoses, including Hunter syndrome and Hurler disease • (E77) Glycoprotein storage disorders • (E77.0-E77.1, E75.11) Mucolipidoses; Mucolipidosis IV is a gangliosidosis Also, glycogen storage disease type II (Pompe disease) is a defect in lysosomal metabolism as well, although it is otherwise classified into E74.0 in ICD-10. Cystinosis is an lysosomal storage disease characterized by the abnormal accumulation of the amino acid cystine. By type of defect protein Alternatively to the protein targets, lysosomal storage diseases may be classified by the type of protein that is deficient and is causing buildup. Lysosomal storage disorders Lysosomal storage diseases include: ==Signs and symptoms==

The symptoms of lysosomal storage diseases vary depending on the particular disorder and other variables such as the age of onset, and can be mild to severe. They can include developmental delay, movement disorders, seizures, dementia, deafness, and/or blindness. Some people with lysosomal storage diseases have enlarged livers or spleens, pulmonary and cardiac problems, and bones that grow abnormally. ==Diagnosis==

The majority of patients are initially screened by enzyme assay, which is the most efficient method to arrive at a definitive diagnosis. In some families where the disease-causing mutations are known, and in certain genetic isolates, mutation analysis may be performed. In addition, after a diagnosis is made by biochemical means, mutation analysis may be performed for certain disorders. ==Treatment==

No cures for lysosomal storage diseases are known, and treatment is mostly symptomatic, although bone marrow transplantation and enzyme replacement therapy (ERT) have been tried with some success. ERT can minimize symptoms and prevent permanent damage to the body. In addition, umbilical cord blood transplantation is being performed at specialized centers for a number of these diseases. In addition, substrate reduction therapy, a method used to decrease the production of storage material, is currently being evaluated for some of these diseases. Furthermore, chaperone therapy, a technique used to stabilize the defective enzymes produced by patients, is being examined for certain of these disorders. The experimental technique of gene therapy may offer cures in the future. Ambroxol has recently been shown to increase activity of the lysosomal enzyme glucocerebrosidase, so it may be a useful therapeutic agent for both Gaucher disease and Parkinson's disease. Ambroxol triggers the secretion of lysosomes from cells by inducing a pH-dependent calcium release from acidic calcium stores. Hence, relieving the cell from accumulating degradation products is a proposed mechanism by which this drug may help. ==History==

Tay–Sachs disease was the first of these disorders to be described, in 1881, followed by Gaucher disease in 1882. In the late 1950s and early 1960s, de Duve and colleagues, using cell fractionation techniques, cytological studies, and biochemical analyses, identified and characterized the lysosome as a cellular organelle responsible for intracellular digestion and recycling of macromolecules. This was the scientific breakthrough that would lead to the understanding of the physiological basis of the lysosomal storage diseases. Pompe disease was the first disease to be identified as an lysosomal storage disease in 1963, with L. Hers reporting the cause as a deficiency of α-glucosidase. Hers also suggested that other diseases, such as the mucopolysaccharidosis, might be due to enzyme deficiencies. ==See also==