About Lysosomal Storage Disorders
Disease Classification 
History of the LSD Class [1]Symptoms of some lysosomal storage disorders were first identified as early as the 1880s, and by the early 1900s many LSDs had been described and classified--although the lysosome itself was not discovered until 1955. Many LSDs were identified before their biochemical and genetic basis was fully understood, so they received common names (for example, after the discovering physician). Later, an additional, more clinically descriptive name often came into use.
By the 1960s the role of lysosomes in cellular digestion and substrate management was well understood, and Pompe became the first disease formally recognized as a lysosomal storage disorder. By the 1970s the scientific community had recognized many more LSDs as such and had begun identifying and classifying the specific enzymatic problems. Sub-Categories
Every LSD results from a problem with the lysosomal process by which enzymes rid cells of substrate. Lysosomes contain about 40 different hydrolytic enzymes, produced in cell cytoplasm and each responsible for breaking down a particular substrate. When a lysosomal enzyme (or another type of enzyme that directs it) is deficient or malfunctioning, the substrate it targets accumulates, interfering with normal cellular activity.[2]
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Healthy cell vs. LSD cell with accumulated substrate |
LSDs can be broken down further into sub-categories[1] based on the type of enzymatic defect and/or stored substrate product. For example, the mucopolysaccharidoses (the “MPS” diseases) are grouped together because each results from an enzyme deficiency that causes accumulation of a particular glycosaminoglycan substrate.
Following are the eight LSD sub-categories used in this site and the diseases that fall under them[1] (linking to each disease’s fact sheet). Defective metabolism of glycosaminoglycans (also known as the “mucopolysaccharidoses”)
MPS I | MPS II | MPS III | MPS IV | MPS VI | MPS VII Defective degradation of glycan portion of glycoproteins
aspartylglucosaminuria | fucosidosis, type I | fucosidosis, type II | mannosidosis | sialidosis, type I | sialidosis, type II Defective degradation of glycogen
Pompe disease Defective degradation of sphingolipid components
acid sphingomyelinase deficiency | Fabry disease | Farber disease | Gaucher disease, type I | Gaucher disease, type II | Gaucher disease, type III | GM1 gangliosidosis, type I | GM1 gangliosidosis, type II | GM1 gangliosidosis, type III | Tay-Sachs disease, type I | Tay-Sachs disease, type II | Tay-Sachs disease, type III | Sandhoff disease | Krabbé disease | metachromatic leukodystrophy, type I | metachromatic leukodystrophy, type II | metachromatic leukodystrophy, type III Defective degradation of polypeptides
pycnodysostosis Defective degradation or transport of cholesterol, cholesterol esters, or other complex lipids
neuronal ceroid lipofuscinosis, type I | neuronal ceroid lipofuscinosis, type II | neuronal ceroid lipofuscinosis, type III | neuronal ceroid lipofuscinosis, type IV Multiple deficiencies of lysosomal enzymes
galactosialidosis | mucolipidosis II | mucolipidosis III Transport and trafficking defects
cystinosis | mucolipidosis IV | infantile sialic acid storage disease (ISSD) | Salla disease
1. Wilcox, WR. Lysosomal Storage Disorders: The Need for Better Pediatric Recognition and Comprehensive Care. Journal of Pediatrics; May 2004: S3-S14.
2. Meikle, PJ, et al. Prevalence of Lysosomal Storage Disorders. JAMA; 281: 249-254 |
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