 | This article needs editing for compliance with Wikipedia's Manual of Style. In particular, it has problems with not using MEDMOS.(July 2017) |
| Gangliosidosis | |
|---|---|
| Specialty | Endocrinology  |
Gangliosidosis contains different types of lipid storage disorders [1] caused by the accumulation of lipids known as gangliosides. There are two distinct genetic causes of the disease. Both are autosomal recessive and affect males and females equally.
Tay–Sachs disease is a genetic disorder that results in the destruction of nerve cells in the brain and spinal cord. The most common form is infantile Tay–Sachs disease which becomes apparent around three to six months of age, with the baby losing the ability to turn over, sit, or crawl. This is then followed by seizures, hearing loss, and inability to move, with death usually occurring by the age of three to five. Less commonly, the disease may occur in later childhood or adulthood. These forms tend to be less severe, but the juvenile form typically results in death by age 15.
Lysosomal storage diseases are a group of about 50 rare inherited metabolic disorders that result from defects in lysosomal function. Lysosomes are sacs of enzymes within cells that digest large molecules and pass the fragments on to other parts of the cell for recycling. This process requires several critical enzymes. If one of these enzymes is defective due to a mutation, the large molecules accumulate within the cell, eventually killing it.
The Portuguese Water Dog originated from the Algarve region of Portugal. From there the breed expanded to all around Portugal's coast, where they were taught to herd fish into fishermen's nets, retrieve lost tackle or broken nets, and act as couriers from ship to ship, or ship to shore. Portuguese Water Dogs rode in fishing trawlers as they worked their way from the Atlantic waters of Portugal to the waters off the coast of Iceland fishing for cod.
Glycolipids are lipids with a carbohydrate attached by a glycosidic (covalent) bond. Their role is to maintain the stability of the cell membrane and to facilitate cellular recognition, which is crucial to the immune response and in the connections that allow cells to connect to one another to form tissues. Glycolipids are found on the surface of all eukaryotic cell membranes, where they extend from the phospholipid bilayer into the extracellular environment.
Glycosphingolipids are a subtype of glycolipids containing the amino alcohol sphingosine. They may be considered as sphingolipids with an attached carbohydrate. Glycosphingolipids are a group of lipids and are a part of the cell membrane. They consist of a hydrophobic ceramide part and a glycosidically bound carbohydrate part. This oligosaccharide content remains on the outside of the cell membrane where it is important for biological processes such as cell adhesion or cell–cell interactions. Glycosphingolipids play also important role in oncogenesis and ontogenesis.
A ganglioside is a molecule composed of a glycosphingolipid with one or more sialic acids linked on the sugar chain. NeuNAc, an acetylated derivative of the carbohydrate sialic acid, makes the head groups of gangliosides anionic at pH 7, which distinguishes them from globosides.
Numerous genetic disorders are caused by errors in fatty acid metabolism. These disorders may be described as fatty oxidation disorders or as a lipid storage disorders, and are any one of several inborn errors of metabolism that result from enzyme defects affecting the ability of the body to oxidize fatty acids in order to produce energy within muscles, liver, and other cell types.
GM2-gangliosidosis, AB variant is a rare, autosomal recessive metabolic disorder that causes progressive destruction of nerve cells in the brain and spinal cord. It has a similar pathology to Sandhoff disease and Tay–Sachs disease. The three diseases are classified together as the GM2 gangliosidoses, because each disease represents a distinct molecular point of failure in the activation of the same enzyme, beta-hexosaminidase. AB variant is caused by a failure in the gene that makes an enzyme cofactor for beta-hexosaminidase, called the GM2 activator.
A lipid storage disorder is any one of a group of inherited metabolic disorders in which harmful amounts of fats or lipids accumulate in some body cells and tissues. People with these disorders either do not produce enough of one of the enzymes needed to metabolize and break down lipids or, they produce enzymes that do not work properly. Over time, the buildup of fats may cause permanent cellular and tissue damage, particularly in the brain, peripheral nervous system, liver, spleen, and bone marrow.
Sphingolipidoses are a class of lipid storage disorders or degenerative storage disorders caused by deficiency of an enzyme that is required for the catabolism of lipids that contain ceramide, also relating to sphingolipid metabolism. The main members of this group are Niemann–Pick disease, Fabry disease, Krabbe disease, Gaucher disease, Tay–Sachs disease and metachromatic leukodystrophy. They are generally inherited in an autosomal recessive fashion, but notably Fabry disease is X-linked recessive. Taken together, sphingolipidoses have an incidence of approximately 1 in 10,000, but substantially more in certain populations such as Ashkenazi Jews. Enzyme replacement therapy is available to treat mainly Fabry disease and Gaucher disease, and people with these types of sphingolipidoses may live well into adulthood. The other types are generally fatal by age 1 to 5 years for infantile forms, but progression may be mild for juvenile- or adult-onset forms.
The GM2 gangliosidoses are a group of three related genetic disorders that result from a deficiency of the enzyme beta-hexosaminidase. This enzyme catalyzes the biodegradation of fatty acid derivatives known as gangliosides. The diseases are better known by their individual names: Tay–Sachs disease, AB variant, and Sandhoff disease.
The GM1 gangliosidoses are caused by a deficiency of beta-galactosidase, with resulting abnormal storage of acidic lipid materials in cells of the central and peripheral nervous systems, but particularly in the nerve cells.
GM1 (monosialotetrahexosylganglioside) the "prototype" ganglioside, is a member of the ganglio series of gangliosides which contain one sialic acid residue. GM1 has important physiological properties and impacts neuronal plasticity and repair mechanisms, and the release of neurotrophins in the brain. Besides its function in the physiology of the brain, GM1 acts as the site of binding for both cholera toxin and E. coli heat-labile enterotoxin.
Hexosaminidase is an enzyme involved in the hydrolysis of terminal N-acetyl-D-hexosamine residues in N-acetyl-β-D-hexosaminides.
Hexosaminidase A , also known as HEXA, is an enzyme that in humans is encoded by the HEXA gene, located on the 15th chromosome.
GM2 is a type of ganglioside. G refers to ganglioside, the M is for monosialic, and 2 refers to the fact that it was the second monosialic ganglioside discovered. It is associated with GM2 gangliosidoses such as Tay–Sachs disease.
A cherry-red spot is a finding in the macula of the eye in a variety of lipid storage disorders and in central retinal artery occlusion. It describes the appearance of a small circular choroid shape as seen through the fovea centralis. Its appearance is due to a relative transparency of the macula; storage disorders cause the accumulation of storage material within the cell layers of the retina, however, the macula, which is relatively devoid of cellular layers, does not build up this material, and thus allows the eye to see through the macula to the red choroid below.
The cell membrane is a biological membrane that separates the interior of all cells from the outside environment which protects the cell from its environment. The cell membrane consists of a lipid bilayer, including cholesterols that sit between phospholipids to maintain their fluidity at various temperatures. The membrane also contains membrane proteins, including integral proteins that go across the membrane serving as membrane transporters, and peripheral proteins that loosely attach to the outer (peripheral) side of the cell membrane, acting as enzymes shaping the cell. The cell membrane controls the movement of substances in and out of cells and organelles. In this way, it is selectively permeable to ions and organic molecules. In addition, cell membranes are involved in a variety of cellular processes such as cell adhesion, ion conductivity and cell signalling and serve as the attachment surface for several extracellular structures, including the cell wall, the carbohydrate layer called the glycocalyx, and the intracellular network of protein fibers called the cytoskeleton. In the field of synthetic biology, cell membranes can be artificially reassembled.
Substrate presentation is a biological process that activates a protein. The protein is sequestered away from its substrate and then activated by release and exposure of the protein to its substrate. A substrate is typically the substance on which an enzyme acts but can also be a protein surface to which a ligand binds. The substrate is the material acted upon. In the case of an interaction with an enzyme, the protein or organic substrate typically changes chemical form. Substrate presentation differs from allosteric regulation in that the enzyme need not change its conformation to begin catalysis. Substrate presentation is best described for nanoscopic distances.
PIP2 domains are a type of cholesterol-independent lipid domain formed from phosphatidylinositol (e.g.,) and positively charged proteins in the plasma membrane. They tend to inhibit GM1 lipid raft function.
| Classification | |
|---|---|
| External resources |
| National libraries | |
|---|---|
| Other | |
 | This article about an endocrine, nutritional, or metabolic disease is a stub. You can help Wikipedia by expanding it. |