Lipids classification to Lipid Storage Diseases

Lipid storage diseases, or the lipidoses, are a group of inherited metabolic disorders in

which harmful amounts of fatty materials (lipids) accumulate in various cells and tissues in the

body.  People with these disorders either do not produce enough of one of the enzymes needed to

break down (metabolize) lipids or they produce enzymes that do not work properly.  Over time,

this excessive storage of fats can cause permanent cellular and tissue damage, particularly in the

brain, peripheral nervous system (the nerves from the spinal cord to the rest of the body), liver,

spleen, and bone marrow. Lipid storage disorders are a family of diverse diseases related by their

molecular pathology. In each disorder, a deficiency of a lysosomal hydrolase is inherited, which

leads to lysosomal accumulation of the enzyme's specific sphingolipid substrate. Lipid substrates

share a common structure, including a ceramide backbone (2-N-acyl-sphingosine), in which

various sphingolipids are derived by substitution of hexoses, phosphorylcholine, or one or more

sialic acid residues on terminal hydroxyl groups of the ceramide molecule. Pathways of

glycosphingolipid metabolism in both nervous tissue and visceral organs are elucidated, and for

each catabolic step, a genetically determined metabolic derangement is identified.

Metabolism is the process your body uses to make energy from the food you eat. Food is

made up of proteins, carbohydrates, and fats. Chemicals in your digestive system (enzymes)

break the food parts down into sugars and acids, your body's fuel. Your body can use this fuel

right away, or it can store the energy in your body tissues. If you have a metabolic disorder,

something goes wrong with this process. Lipid metabolism disorders, such as Gaucher disease

and Tay-Sachs disease, involve lipids. Lipids are fats or fat-like substances. They include oils,

fatty acids, waxes, and cholesterol. If you have one of these disorders, you may not have enough
enzymes to break down lipids. Or the enzymes may not work properly and your body can't

convert the fats into energy. They cause a harmful amount of lipids to build up in your body.

Over time, that can damage your cells and tissues, especially in the brain, peripheral nervous

system, liver, spleen, and bone marrow. Many of these disorders can be very serious, or

sometimes even fatal. These disorders are inherited. Newborn babies get screened for some of

them, using blood tests. If there is a family history of one of these disorders, parents can get

genetic testing to see whether they carry the gene. Other genetic tests can tell whether the fetus

has the disorder or carries the gene for the disorder.

Lysosomal lipid storage diseases, or lipidoses, are inherited metabolic disorders in which

typically lipids accumulate in cells and tissues. Complex lipids, such as glycosphingolipids, are

constitutively degraded within the endolysosomal system by soluble hydrolytic enzymes with the

help of lipid binding proteins in a sequential manner. Because of a functionally impaired

hydrolase or auxiliary protein, their lipid substrates cannot be degraded, accumulate in the

lysosome, and slowly spread to other intracellular membranes. In Niemann-Pick type C disease,

cholesterol transport is impaired and unesterified cholesterol accumulates in the late endosome.

In most lysosomal lipid storage diseases, the accumulation of one or few lipids leads to the

precipitation of other hydrophobic substances in the endolysosomal system, such as lipids and

proteins, causing a “traffic jam.” This can impair lysosomal function, such as delivery of

nutrients through the endolysosomal system, leading to a state of cellular starvation. Therapeutic

approaches are currently restricted to mild forms of diseases with significant residual catabolic

activities and without brain involvement.

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